Haematology

Question 1

What is Virchow’s triad?

Answer 1

Vessel wall, blood, flow

Question 2

What are the consequences of thromboembolism?

Answer 2

Death

Recurrence

Thrombophlebitic syndrome

Pul HTN

Question 3

Blood in virchow’s triad

Answer 3

Viscosity: Hct, protein/paraprotein

Platelet count

Coagulation system: triggered by TF, generates thrombin, thrombin converts fibrinogen to fibrin (the clot)

Question 4

Draw the blood coagulation pathway

Answer 4

Question 5

How is the blood coagulation pathway regulated by thrombin? (draw)

Answer 5

Question 6

How is the blood coagulation pathway regulated by Protein C? (draw)

Answer 6

Question 7

What are the procoagulant factors?

Anticoagulant factors?

Answer 7

Question 8

What is factor 5 Leidin?

Answer 8

Factor V Leiden thrombophilia[1] is a genetic disorder of blood clotting. Factor V Leiden is a variant (mutated form) of human factor V (one of several substances that helps blood clot) that causes an increase in blood clotting (hypercoagulability). In this disorder, the Leiden variant of factor V cannot be inactivated by the anticoagulant protein activated protein C, so clotting is encouraged. (With this mutation, the protein secreted that helps blood not clot is unable to do so, and therefore clotting is more likely) [2] Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorderamongst ethnic Europeans

Question 9

What is the most common hereditary cause of hypercoagulability in ethnic Europeans?

Answer 9

FVL

Question 10

Vessel wall in Virchow’s triad

Answer 10

Expresses anticoagulatn molecules: thrombomodulin, endoethlial protein C R, TF pathway inhibotr, heparans

Does not express TF

Secretes antiplatelet factors: prostacyclin, NO

Question 11

What happens with vessel wall inflammation/injury?

Answer 11

Makes the wall prothrombotic

Can be caused by infection, malignancy, vasculitis, trauma

Effects: downregulation of anticoagulant factors (TM), upregulation of adhesion molecules, expression of TF, reduced production of prostacycline

Question 12

What are the implications of thrombosis in Cancer?

Answer 12

l In the 12 months after idiopathic thrombosis, approximately 10% of patients will have cancer diagnosed.

lSimple tests, CXR, FBC, CRP, profile, urine will detect ~50% of these.

lMost malignancies presenting with thrombosis have a poor prognosis.

¨RR is ~7 for patients with active cancer

¨~ 20% of all VTE occur in patients with cancer

¨% incidence of VTE in year after cancer diagnosis

NB there is variation with type of cancer and extent of disease

Question 13

Which cancer has largest effect on incidence of VTE?

Answer 13

Pancreas

Question 14

How does stasis promote thrombosis?

Answer 14

Accumulation of activated factors

Promotes platelet adhesion

Promotes leukocyte adhesion and transmigration

Hypoxia produces inflammatory effect on endothelium

Question 15

What are the causes of blood stasis?

Answer 15

Immobility: Sx, paraparesis, travel

Compression: tumour, pregnancy

Viscosity: polycythaemia, paraprotein

Congenital: vascular abnormalities

Question 16

When does the risk of PE after air travel start?

Answer 16

3-6h

Greatest >12h

Question 17

Implications of combined thrombotic risks

Answer 17

Thrombotic factors often combine to produce thrombosis, can have synergistic effect

Have powerful interactions which are unpredictable

e.g.

Pregnancy, increased VIII, fibrinogen, Decreased protein S, Flow

Malignancy: TF on tumour, inflam, flow

Sx: trauma, inflam, flow

Question 18

What are the principles of managing VTE

Answer 18

ST prevention: during periods of high risk

Immediate treatment: preventing extension and embolisation

LT prevention

Anticoagulants

Question 19

Anticoagulant therapy:

High dose?

Low dose?

Answer 19

High dose: therapeutic

Low dose: prophylactic

Question 20

What are the traditional/standard anticoagulants?

Answer 20

Heparin: unfractioneated/LMWH/Direct acting anti-Xa and anti-IIa: IMMEDIATE

Warfarin: DELAYED

Question 21

Administration of different types of heparin?

What are their actions?

Consequence?

Answer 21

Unfractionated: IV

LMWH: sub cut

Pentasacchadie: sub cut

All act by potentiating antithrombin

Provide immediate effect: e.g. for treatment of thrombosis, long term disadvantages include daily injections and risk of osteoporosis

Question 22

Monitoring of heparin therapy?

Answer 22

LMWH: reliabl pharmacokinetics so not usually required except in renal failure, extemes of weight or risk, unusual conditions.

Monitor using anti-Xa

Unfractionated heparian: unreliable kinetics

Always moinotr therapeutic levels with APTT or anti-Xa

Question 23

What are the anti-Xa direct acting anticoagulants?

Answer 23

Rivaroxaban, apixaban, edoxaban

Question 24

What are the direct acting anti-IIa anticoagulants?

Answer 24

Dabigatran

Question 25

What are the properties of the direct acting anticoagulants?

Answer 25

Oral Immediate action peaak within 3-4h Short t1/2 No monitoring Limited licensed indications thus far

Question 26

What is the use of Warfarin? Action? Therefore What is the impact?

Answer 26

Given orally Indirect effect by preventing Vit K recycling. Therefore delayed onset of action Levels of procoagulants falls: II, VII, IX, X protein C and protien S (anticoagulant factors) also fall

Question 27

Monitoring of Warfarin? What are the issues with Warfarin therapy? Implications in pregnancy?

Answer 27

Always essential through measuring INR. Derived from PT Difficulty as Warfarin has numerous interactions e.g. dietary K, variable absorption, interaction with other drugs Teratogenic

Question 28

Action of heparin vs warfarin vs doac

Answer 28

Cofactor for AT vs Vit K antag vs direct enzyme inhibition

Question 29

Reversal of heparin warfarin DOAC?

Answer 29

Protamine Factor concentrate, vit K none atm

Question 30

Pregnancy: heparin warfarin DOAC

Answer 30

Heparin: safe Warfarin: teratogenic DOAC: no data- avoid

Question 31

Who receives thromboprophylaxis?

Answer 31

People at risk: Sx, immobility, pregnancy, general medical inpatients

Question 32

What is used for thromboprophylaxis? And the features of each Rx?

Answer 32

LMWH: daily, e.g. tinzaparine 4500u/ Clexane 40mg Rivaroxaban TED stocking for Sx or if heparin contraindicated?

Question 33

Bleeding risk assessment for anticoagulant therapy Patient factors

Answer 33

Patient: bleeding diathesis, platelt count \<100, acute CVA in prevous month (eith categrory) BP \>200 / \>120 Severe liver disease severe renal disease Active bleeding anticoagulant or antiplatelet therapy

Question 34

Bleeding risk assessment for anticoagulant therapy Procedure features

Answer 34

Neuro, spinal, eye Sx Other with high bleeding risk LP, spinal/ epi in previous 4 hours

Question 35

What is essential for treatment of DVT/PE What is the approach

Answer 35

Immediate anticoagulation LMWH (175u/kg) + Warfarin (some NOACS e.g. rivaroxaban now lciensed). Stop LMWH when INR in therapeutic range Continue for 3-6m Patients with cancer continue LMWH not Warfarin Elasticated stocking for 2y to prevent postphlebitic syndrome

Question 36

Duration of LMWH/Warfarin based on cause 1st VTE, known cause:

Answer 36

3m

Question 37

Duration of LMWH/Warfarin based on cause Cancer

Answer 37

LMWH 3-6m

Question 38

Duration of LMWH/Warfarin based on cause 1st VTE unknown cause

Answer 38

3-6m Warfarin, potentially lifelong

Question 39

Duration of LMWH/Warfarin based on cause 1st VTE in thrombophilic patient

Answer 39

3m Warfarin ?lifelong

Question 40

Duration of LMWH/Warfarin based on cause Recurrent VTE

Answer 40

lifelong Warfarin

Question 41

What may also be indicated following VTE?

Answer 41

TEDS to prevent postphlebitic syndrome

Question 42

Use of thrombolysis in VTE

Answer 42

Only for life threatening PE or limb threating DVT Risk fof ICH ~4% Reduces subsequent post=phlebitic syndrome

Question 43

PE/DVT risk of recurrence

Answer 43

Some studies suggest higher risk of recurrence with PE but some not Generally VTE means increased risk of recurrence

Question 44

Anticoagulation and recurrence after first VTE with minor precipitant (COCP, flights trauma) length of therapy

Answer 44

Generally 3m adequate

Question 45

What are the inherited risk factors for VTE?

Answer 45

Antithrombin deficiency Protein C D Protein S D Factor V Leiden, resistance to protein C Prorthrombin Lupus anticoagulant Coag excess: VIII (10%) 11 (2%), Fibrinogen

Question 46

What is the most common coagulant excess in inherited VTE?

Answer 46

Factor VIII (10%)

Question 47

What are the acquired risk factors for VTE?

Answer 47

Age, obesity Previous DVT, PE Immobilisation Major Sx, esp ortho. \>30mins, plaster cast immobilisation Long distance travel Malignancy, esp pacnreas NB 10% idiopathic VTE due to Ca Pregnancy, COCP, HRT Antiphospholipid syndrome Polycythaemia Thrombocythaemia

Question 48

What is antiphospholipid syndrome?

Answer 48

Antiphospholipid syndrome orantiphospholipid antibody syndrome (APS or APLS), or often also Hughes syndrome, is an autoimmune,hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries andveins as well as pregnancy-related complications such asmiscarriage, stillbirth, preterm delivery, and severepreeclampsia.

Question 49

Features of Heparin: MOA LMWH administration Unfractionated administration Antidote SEs

Answer 49

Potentiates antibthrombin III which inactivates thrombin and factors 9, 10, 11 Given SC daily, does not require monitoring except late pregnancy and reanl failure IV loading dose then infusion, monitor APTT Antidote: protamine sulphate Side effects: heparin induced thrombocytopaenia, osteoporosis (both more common with UFH)

Question 50

Indications for target INR of 2.5?

Answer 50

1st episode DVT or PE, AF (2-3) Cardiomyopathy, symptomatic inherited thrombophilia Mural thrombus Cardioversion

Question 51

Indications for target INR 3.5?

Answer 51

Recurrent DVT or PE, mechanical prosthetic valve (2.5-3.5) Coronary artery graft thrombosis Antiphospholipid syndrome

Question 52

Mx of INR 5-8 no bleeding

Answer 52

Withold doses, reduce maintenance, restart when INR \<5

Question 53

Mx of INR 5-8 minor bleeding

Answer 53

Stop warfarin, VIt K slow IV. Restart when INR \<5

Question 54

Mx INR \>8 no bleed/minor bleed

Answer 54

Stop Warfarin Vit K oral/IV no bleeding/if risk factors for bleeding Daily INR monitoring

Question 55

Mx of major bleeding with raised INR including ICH

Answer 55

Stop warfarin Give prothrombin complex concentrate If unavailable give FFP Also give Vit K IV

Question 56

What is the relationship between Cancer and anaemia? Give some examples of anaemia as the manifestation of malignancy NB

Answer 56

Many causes for cancer associated anaemia Many cases of anaemia are the first presentation of ca: Fe deficiency Anaemia of inflammation (chronic disease) Leucoerythroblastic anaemia Haemolytic anaemias: autoimmune, microangiopathic Ca may also cause 2o polycythaemia e.g. RCC and HCC

Question 57

Fe deficiency and cancer Cause Laboratory findings

Answer 57

Occult blood: GI cancer: gastric, colonic/rectal Urinary tract cancers: RCC, bladder Reduced Ferritin, transferrin saturation Raised TIBC Fe deficiency is bleeding until proven otherwise

Question 58

What is leucoerythoblastic anaemia? Morphological features

Answer 58

Red and white cell precursor anaemia (variable degree of anaemia) Morphological features: teardrop RBCs (+ aniso and poikilocytosis), Nucleated RBCs, immature myeloid cells

Question 59

What does this blood film schow?

Answer 59

Leucoerythroblastic film Tear drop poikilocytes Nucleated RBC Myelocyte

Question 60

Outline the principle causes of a leucoerythroblastic film

Answer 60

Question 61

What are the features of myelofibrosis?

Answer 61

Massive splenomegaly Dry tap on BM aspirate

Question 62

What are the common laboratory features of haemolytic anaemia of any aetiology?

Answer 62

Anaemia (may be compensated) Reticulocytosis Raised UNCONJUGATED bilirubin Raised LDH Reduced haptoglobins

Question 63

What are the 2 pathogenci groups of haemolytic anaemia

Answer 63

Inherited: all due to defects of the red cell Acquired: defects of the environment in which the red cell finds itself (except Paroxysmal Nocturnal Haemolytic anaemia)

Question 64

What are the three components of of a red cell and how are they affected by iHA

Answer 64

Membrane Spherocytosis, elliptocytosis Hb: Structural (SCD) Quantitative (thallassaemias) Enzymes: G6PD

Question 65

What are the only two types of acquired HA What is the one test that distinguishes between them?

Answer 65

Immune Non-immune DAT (Coomb's test)

Question 66

What are the causes of immune HA?

Answer 66

Auto-immune: allo-immune/blood transfusion. Spherocytes, DAT +ve Associated systemic disorder: Cancer of the immune system: lymphoma Disease of hte immune system: SLE Infection: disturbing the immune system

Question 67

Features of autoimmune haemolysis Positive DAT means?

Answer 67

Anaemia Reticuloytosis Raised LDH Positive DAT Either idiopathic or there is an underlying lymphoma/CLL/systemic autoimmune disease e.g. SLE

Question 68

What are the two main causes of spherocytes How can they be distinguished between

Answer 68

They are most commonly found in immunologically-mediated hemolytic anemias and in hereditary spherocytosis, but the former would have a positivedirect Coombs test and the latter would not. The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cycle whereby the body destroys its own blood supply (auto-hemolysis).

Question 69

What does this blood film show?

Answer 69

Spherocytes

Question 70

What are the causes of acquired haemolytic anaemia: Non-Immune

Answer 70

Infection: Malaria Micro-angiopathic HA Red cell fragments Low platelets DIC/bleeding Underlying adenocarcinoma

Question 71

Features on this film What does it show?

Answer 71

RBC fragments, thrombocytopenia MAHA

Question 72

Micro-angiopathy in malignancy (pathogenesis)

Answer 72

Adenocarcinomas, low grade DIC Platelet consumption Fibrin deposition and degradation Red cell fragmentation Bleeding

Question 73

Jaundice/Anaemia/Raised LDH How would you exclude or diagnose? Lymphoma with liver involvement

Answer 73

Bilirubin conjugated/DAT negative/CT scan liver deposits/BM involved-infiltrated

Question 74

Jaundice/Anaemia/Raised LDH How would you exclude or diagnose? Lymphoma with nodes compressing the bile duct

Answer 74

Bilirubin conjugated/DAT negative/CT scan nodes around porta-hepatis/BM involved-infiltrated

Question 75

Jaundice/Anaemia/Raised LDH How would you exclude or diagnose? Lymphoma with auto immune haemolytic anaemia

Answer 75

Bilirubin Unconjugated/DAT positive/CT scan no liver deposits

Question 76

What are the causes of true polycythaemia (raised red cell mass)

Answer 76

2o (raised EPO/inappropriate): HCC, bronchial Ca, RCC Polycythaemia vera: clonal myeloproliferative disorder involving acquired mutaitons in JAK2

Question 77

What are the types of WBC and where are they normal?

Answer 77

Mature Phagocytes: granulocytes, monocytes Immunocytes: lymphocytes Immature Normal in BM in an appropriate%, not normal in PB: Blasts, promyelocytes, myelocytes

Question 78

What does CLL involve?

Answer 78

WBC increased mature cells

Question 79

Answer 79

CLL: Increased WBC mature cells

Question 80

Answer 80

AML: increased immature cells in PB

Question 81

What are the causes of neutrohilia?

Answer 81

Corticosteroids Underlying neoplasia Tissue inflammation e.g. colitis, pancreatitis Myeloproliferative/leukaemic disorders **Infection**

Question 82

What are the causes of neutrophilia in infection?

Answer 82

Localised and systemic infections, acute bacterial, fungal and certain viral

Question 83

What is characteristic of infection with brucella, typhoid and most viruses in terms of FBC

Answer 83

Characteristically do not produce a neutrophilia

Question 84

What are the characteristics of a reactive neutrophilia?

Answer 84

Presence bands Toxic granulation Signs of infection/inflammation

Question 85

What are the characteristics of a malignant neutrophilia

Answer 85

Neutrophilia basophilia plus immature cells and splenomegaly suggests myeloproliferative (CML)

Question 86

Features of CML

Answer 86

Neutrophilia basophilia plus immature cells myelocytes, and splenomegaly. Suggest a myeloproliferative (CML)

Question 87

Neutropenia plus myeloblasts=?

Answer 87

AML

Question 88

Answer 88

Reactive neutrophilia

Question 89

Answer 89

CML

Question 90

What are the causes of a reactive eosinophilia?

Answer 90

Parasitic infestation Allergic disease e.g. asthma, rheumatoid polyarteritis, pulmonary eosinophilia Underllying neoplasms esp. Hodgkins, T-cell NHL Drugs: erythema multiforme

Question 91

What is a malignant cause of eosinophilia

Answer 91

Chronic eosinophilic leukaemia Eosinophils part of the clone

Question 92

FIP1L1-PDGFRa Fusion Gene found in?

Answer 92

Chronic eosinophilic leukaemia

Question 93

Answer 93

Eosinophilia

Question 94

Causes of monocytosis

Answer 94

Rare, seen in certain chronic infections and primary haematological disorders Infections: TB, brucella, typhoid, vidal: CMV, VZV Sarcoid Chronic myelomonocytic leukaemia

Question 95

What are the relevant investigations to interpret a lymphocytosis

Answer 95

Clinical: infection or lhymphoma? Lymphadenopathy or splenomegaly? FBC: degree of lymphocytosis Microscopy/morpology: mature vs immature Flow cytometry: lineage- T or B cells. Stage of differentiation Molecular genetics

Question 96

Causes of reactive lymphocytosis

Answer 96

Infection: EBV, CMV, Toxoplasma, Infectious hepatitis, rubella, herpes Autoimmune Neoplasia Sarcoid

Question 97

Lymphocytosis \>3.5x109/l What could this be?

Answer 97

* EBV viral infection * early CLL

Question 98

Answer 98

CLL

Question 99

Answer 99

ALL

Question 100

What is the principle of flow cytometry

Answer 100

Throughout B cell development, cells at differential stages express different surface antibodies. Flow cytometry separates these cells on the basis of Ab expression

Question 101

What is multiple myeloma?

Answer 101

Neoplastic proliferaiton of bone marrow plasma cells associated with a monoloncal protein in serum and or urine Production of monoclonal Igs: paraprotein IgG most common. Middle-aged to elderly Afrocarribean's have increased incidence

Question 102

CRAB

Answer 102

Clinical features of MM Calcium high Renal failure: plus amyloidosis and nephrotic syndrome Anaemia (and pancytopenia) Bone pain: osteoporosis, osteolytic lesions, fractures + Hyperviscosity syndrome

Question 103

What are the features of symptomatic plasma cell myeloma

Answer 103

Monoclonal protein in the serum and or urine Bone marrow clonal plasma cells or plasmacytoma CRAB

Question 104

What are the features of asymptomatic/smouldering myeloma

Answer 104

Monoclonal protein in serum at myeloma levels (\>30g/l) 10% or more clonal plasma cells in BM No related organ or tissue impairment

Question 105

Px of myeloma

Answer 105

3y with conventional CTx 5y with autlogous stem cell transplation (cure)

Question 106

Epidemiology of MM

Answer 106

M\>F Black\>white Doesn't occur in children 70y/o median diagnosis Increased incidence if first degree relative

Question 107

Ix in MM

Answer 107

Dense narrow band on electrophoreisis Rouleaux on blood film (RBC stacking) Bence-Jones protein in urine Raised ESR (+++) \>10% plasma cells in BM

Question 108

Bence-Jones protein

Answer 108

MM

Question 109

Staining in MM

Answer 109

H&E Immune-peroxidase stain for CD138

Question 110

Bony features of MM

Answer 110

Multiple sjulll lesions Plasmacytoma: malignant plasma cell tumour growing within soft tissue Osteopenia and wedge fractures of hte vertebrae

Question 111

Serum protein electrophoresis

Answer 111

IgG 52% IgA 22% IgM 12 IgE rare

Question 112

What is the staging system for MM?

Answer 112

Durie Salmon

Question 113

What are the crtieria for the staging of Duire Salmon

Answer 113

Hb Serum Ca Bone disease IgG IgA Urine light-chain M-component Stages 1-3 International staging system (ISS): B2-microglobulin Albumin

Question 114

Stage 1 MM

Answer 114

\>10g/dl No bone disease IgG \<50 IgA \<30 \<4mg urine light chain \<3.5B2 microglobulin \>35 albumin

Question 115

Stage 3 MM

Answer 115

Hb \<8.5 Raised Ca Multiple lytic lesions in bone \>70g/dl IgG \>50g/l IgA Urine light chain \>12g Raised B2 microgloublin Hypoalbuminaemia

Question 116

Answer 116

Multiple myeloma

Question 117

What is MGUS?

Answer 117

Monoclonal gammaglobinopathy of unkown significance \<10% plasma cells in marrow \<30h/l monoclonal paraprotein No CRAB Incidental finding progressing to MM at 1-2%/year No therapy needed at this stage Monitor for transformation

Question 118

What is smoldering MM?

Answer 118

Monoclonal gammaglobinopathy of unkown significance \>10% plasma cells in marrow \>30h/l monoclonal paraprotein No CRAB No therapy needed at this stage Monitor for transformation

Question 119

What is Waldenstrom's Macroglobinaemia?

Answer 119

Lymphoplasmacytoid Lymphoma (PLL) Elderly men Low grade NHL: lymphoplasmacytoid cells produce monoclonal serum **IgM** that infiltrates the LNs and BM Weight loss, fatigues, hyperviscosity syndrome Treatment: plasmapheresis for hyperviscosity Chlorambuicl, cyclophosphamide

Question 120

What are the features of hyperviscosity syndrome?

Answer 120

Visual problems, confusion, CCF, muscle weakeness

Question 121

What are the criteria for plasma cell leukaemia?

Answer 121

\>2x10^9 plasma cells in peripheral blood or \>20% of the leukocyte differential count

Question 122

What are the features of systemic amyloidosis?

Answer 122

Ig light chains= paraprotein. Deposition of abn proteniacious substance in tissues Diagnosed via cong-red: APPLE GREEN BIREFRINGENCE Presents with macroglossia, carpal tunnel syndrome, peripheral neuropathy, RF Treatment with CTx or auto-SCT

Question 123

Cong red: apple green birefringence

Answer 123

Amyloidosis

Question 124

What is MP?

Answer 124

6-mercaptopurine

Question 125

What is VAD?

Answer 125

Vincristine Doxorubicin Dexamethasone

Question 126

What is CTD?

Answer 126

Cyclophosphamide Thalidomide Dexamethasone

Question 127

What is MPT?

Answer 127

Melphalan Prednisolone Thalidomide

Question 128

What is the MOA of thalidomide in MM?

Answer 128

Immunomodulatory: alters expression of adhesion molecules, reduces TNF alpha and increases IL-10 leading to increased cell-mediated immunity Inibits angiogenesis and promotes apoptosis of endothelial cells in established angiogenesis Advantages: oral, synergistic effects in combination therapy. Used for relapsed myeloma Toxic, dose-limiting Side effects

Question 129

What are the side effects of thalidomide?

Answer 129

Neuropathy VTE Somnolence Consitpation

Question 130

What is the MOA for Bortezomib

Answer 130

Inactivates Nf-kB by binding to the beta ring of 20S proteosome Good activity, high and rapid response Expensive, toxic

Question 131

What are the toxic effects of Bortezomib?

Answer 131

Neuropathy Systemic toxicity

Question 132

What are some new drugs in the treatment of MM?

Answer 132

Thalidomide Bortezomib Lenalidomide

Question 133

What is the therapy of choice in MM

Answer 133

Alkylating agent +/- prednisolone Maintenance with IFN alpha ASCT curative Bisphosphonates reduce #s and bone pain

Question 134

Treatment of bone disease in MM

Answer 134

Hypercalcaemia: IV fluids, steroids, bisphosphonates Bone pain: pamidronate, zoledronic acid and clodronate.

Question 135

What are the transplant options in MM?

Answer 135

Autologous SCT: treatment of choice for most patients. Collect stem cells and give high dose melphalan Allogenic SCT: decreased deaths due to lower incidence, of infections and interstitial pneumonitis. Consider in patients under 50 with age matched sibling

Question 136

What are the principle causes of mortality in pregnancy?

Answer 136

Genital tract sepsis Eclampsia VTE Amniotic fluid embolism Haemorrhage Ectopic

Question 137

What are the haematological demands of pregnancy

Answer 137

Iron: 300mg for fetus. 500mg for increased maternal cell mass. RDA30mg. WHO recommends 60mg/d Folate: increased requirement due to growth and cell division. Additional 200mcg/d. WHO recommends 400mcg/d

Question 138

RCOG folate recommendations

Answer 138

Before conception and for \>12w gestation 400microg/d

Question 139

What are the risks of Fe deficiency in pregnancy

Answer 139

IUGR Prematuiry PPH

Question 140

What are the blood count changes in pregnancy?

Answer 140

Mild anaemia: dilutional effect, red cell mass rises 120-130%, plasma volume rises 150% Macrocytosis: may be normal or due to folate or B12 deficicency Thrombocytopenia (\<150): can be physiological

Question 141

Causes of thrombocytopenia in pregnancy

Answer 141

Physiological (gestational/incidental thrombocytopenia) Pre-eclampsia ITP MAHA OAll other causes Increased platelet size

Question 142

Plt \<150 in pregnancy

Answer 142

Gestational most likely then ITp then PE

Question 143

Plt \<100 in pregnanc

Answer 143

Gestational most likely cause then pre-ecl then ITP

Question 144

Plt \<70 in pregnancy

Answer 144

ITP = Pre-ecl as most likely cause Then gestational

Question 145

Features of gestational thrombocytopenia

Answer 145

10% physiological decrease Mechanism poorly defined Either dilutional effect or increased consumption Platelet count rises 2-5d post-partum

Question 146

What are the plt cut offs for delivery/epidural

Answer 146

Delivery 50 Epidural 80

Question 147

What are the features of thrombocytopenia in pre-ecl?

Answer 147

50% of pre-eclamptics get therombocytopenia proportional to severity Due to increased activation and consumption Associated with coagulation activation. Incipient DIC, normal PT and APTT. Usually remits following delivery

Question 148

Features of ITP in pregnancy

Answer 148

5% of thrombocytopenia in pregnancy. Can precede pregnancy and start early in gestation

Question 149

Treatment of ITP in pregnancy

Answer 149

IV Ig Steroids Anti-D in Rhesus negative

Question 150

Foetal effects of ITP

Answer 150

Unpredictable when \<20 Check cord blood daily

Question 151

What is MAHA?

Answer 151

Deposition of plt in small BVs. Thrombocytopenia Fragmentation and destruction within the vasculature, results in organ damage: Kidney, CNS (placenta)

Question 152

Blood film in MAHA

Answer 152

Fragments Low plt Polychromasia (increased RBCs)

Question 153

TTP and HUS in pregnancy

Answer 153

More common Not helped by delivery Usually earlier than HELLP, usually in 2nd trimester

Question 154

What is the net effect of coagulation changes in pregnancy?

Answer 154

Procoagulant state: Increased thrombin generation Increased fibrin cleavage Reduced fibrinolysis and interaction with other maternal factors leading to Increased rate of thrombus

Question 155

PE in pregnanc

Answer 155

Risk highest in 40-46w gestation/post-partum then 0-13w

Question 156

Risks in pregnancy for VTE

Answer 156

BMI FH Bed rest Pre-ecl Operative delivery Previous VTE Thrombophilia Age Parity Multiple pregnancy Other medical problems Hyperemesis gravidarum/dehdration. OHSS Unreltaed surgery

Question 157

D-dimer in pregnancy

Answer 157

Already elevated Useless

Question 158

Complications of thrombophilia in pregnancy

Answer 158

Associated with impaired placental circulation Results in: IUGR, recurrent miscarriage, late foetal loss, placental abruption, severe Pre-ecl

Question 159

Which thrombophilias are associated with pregnancy complications?

Answer 159

Antiphospholipid syndrome: recurrent miscarriage and persistent lupus anticoagulant/anticardiolipin Abs AT PC and PS deficiency FVL High protthombin

Question 160

Treatment of APLS

Answer 160

Aspirin Heparin

Question 161

What is the normal blood loss in SVD C-sec

Answer 161

300-500mL 900-1100mL

Question 162

Def: PPH

Answer 162

\>500mL after SVD \>1100mL after C-sec

Question 163

DIC syndromes in pregnancy

Answer 163

DIC precipitated by amniotic fluid embolism Placental abruption Retained dead foetus Pre-eclampsia Sepsis

Question 164

Why does DIC occur in amniotic fluid embolism?

Answer 164

Due to tissue factor in te amniotic fluid

Question 165

Why is Hbopathy screening performed in pregnancy?

Answer 165

To avoid birthds of children with alpha0 thalassamie which die in utero or from hydrops fetalis

Question 166

How is thalassaemia screening stratified?

Answer 166

Based on pregnant women FBC indices FBC indices: MCH \<27: possible thalassameia trait \<25 requires DNA analyiss Ethnic origin

Question 167

Options if hbopathy identified in pregnancy?

Answer 167

Proceed Prenatal Dx at 10-12 CVS Amniocentesis Foetal blood sampling USS

Question 168

Features of SCA and pregnancy

Answer 168

Painful crises become more frequent, anaemia is exaggerated and transfusions are often required Also associated with: Increased risks of hospital admission Post-partum infection IU foetal death IUGR Prematurity Perinatal mortality Pyelonephritis Low birth weight PROM Pre term labour Pre-ecl

Question 169

What immune disorders are significant in pregnancy?

Answer 169

HDN Haemolytic disease of newborn NAITP

Question 170

What is NAITP?

Answer 170

Neonatal alloimmune thrombocytopenia: gaining of Abs to platelets from the mother's circulation Genetic differences lead to Ag expression on the foetal platelets.

Question 171

Signs and symptoms of anaemia

Answer 171

Weakness Pale Tired Cardiac failure SOB Orthopnea PND Swollen ankles Lethargic Decreased exercise times Syncope Palpitations Tachycarida Koilonychia (Fe def.) Glossitis (B12 def) Jaundice (haemolysis) Pale mucous membranes Cardiomegaly CCF

Question 172

Koilonychia in anaemia

Answer 172

Fe deficiency

Question 173

Glossitis in anaemia

Answer 173

B12 deficiency

Question 174

Jaundice in anaemia

Answer 174

Haemolysis

Question 175

Causes of microcytic anaemia

Answer 175

Fe deficiency Anaemia of chronic disease Thalassaemia

Question 176

Features of reticulotcytosis

Answer 176

Normal resposne to anaemia- haemolysis, haemorrhage and haematinics Absent reticulocytosis if inadequate or bone barrow failure or after acute haemorrhage as takes 6 hours. Pushes MCV up

Question 177

What does reticulocytosis do to MCV?

Answer 177

Pushes t up

Question 178

Features of Fe deficiency

Answer 178

Blood film: pencil cells, anisocytosis, poikilocytosis, hypochromic Low ferritin, low transferrin saturation Establish source of blood

Question 179

Blood film: pencil cells, anisocytosis, poikilocytosis, hypochromic

Answer 179

Fe deficiency

Question 180

Causes of pancytopenia

Answer 180

BM failure Lymphoma/leukaemia Aplastic anaemia RTx, CTx Myelofibrosis B12/Folate deficiency

Question 181

Ix of pancytopenia

Answer 181

Bone marrow aspirate Blood film B12 and folate levels

Question 182

Ix of low platelets

Answer 182

Coagulation screen Blood film BM aspirate ANA/RAPA/Antiplatelet Ab/HIV test D-dimer Fibrinogen Blood cultures/CSF/MSU LFTs

Question 183

DIC=

Answer 183

Anaemia and thrombocytopenia

Question 184

Mx of DIC

Answer 184

Antibiotics Blood products; RBCs, platelets, croprecipitate, FFP Regular bloods to assess response to products

Question 185

Auer rod=

Answer 185

Accumulation of granules in myeloid cells AML

Question 186

How is testing of blood performed?

Answer 186

Use known anti-A, anti-B and anti-D reagents to test for ABO and RhD group Positive test causes agglutination. If the RBCs have agglutinated they are seen at the top of the column

Question 187

What are the methods for testing blood type?

Answer 187

Column agglutination Abbreviated testing Automated blood grouping Ab screening

Question 188

Abbreviated blood group testing

Answer 188

Blood added to card or tube and reacts with rapid reagents

Question 189

Automated blood grouping

Answer 189

Bar coded samples with image analysis, quicker to interpret with no manual steps

Question 190

What is the purpose of the antibody screen?

Answer 190

Need to identify clinically significant antibodies and transfuse Abs negative for that antigen. Thisis to prevent delyed haemolytic transfusion reactions. Can be done using the indirect antiglobulin technique. Test the pateint's plasma with 2 or 3 RBCs that contain all the important antigens. Screen by incubating pateint's plasma with screening cells

Question 191

Cross-matching

Answer 191

Blood label: donor RBCs labelled with ABO + D type. And other Rh Ags and K Select blood.

Question 192

What is the IAT?

Answer 192

Patient plasma incubated with donor red cells at 37deg for 30-40mins This will pick up antibody antigen reactions that could cause extravascular haemolysis. Need to add antiglobulin reagenet

Question 193

Immediate spin cross matching

Answer 193

Saline, room T, incubate patients plasmawith donor cells for 5 minutes and spin. This will detect ABO incompatibility. IgM anti-A and or IgM anti-B will bind to RBCs, fix complement and cause cell lysis

Question 194

What is electronic crossmatch

Answer 194

LIMS automatically determines compataibility without serological testing of donor cells against patient plasma

Question 195

What is MSBOS

Answer 195

Negotiations between surgeons and transufion lab for predictable blood loss from surgery

Question 196

Group and Save or Group and Crossmatch

Answer 196

Pt details Indication for transfusion and urgency Number of RBCs to crossmatch or group and save Previous transfusions and date Special requirements: irradiation, CMV negative Location of patient Handwrite on blood sample taken.

Question 197

Methods of autologous blood transfusion

Answer 197

Pre-operative autologous deposit of blood, shelf life 5w, taken at weekly intervals with Fe supplementation. Cell salvage: use a machine to suck up blood during surgery. Can't do this if there is malignant or bacterial contaminant. Used in obstetric and vascular/bloody surgery

Question 198

What is HDN

Answer 198

Person may form red cell Ab through blood transufion or if fetal cells enter woman's circulation during pregnancy or delivery. Some Ags are more likely to form Abs than other If maternal Ab level is high, it can destroy fetal red cells if they have corresponding red cell Ag. Leads to HDN (fetal anaemia and jaundice) Only IgG can cross the placenta. Anti-D often most responsible. Other Ab= anti-C, anti-K, IgG ABO

Question 199

Rhesus D isoimmunisation

Answer 199

1st preg: Rhesus +ve fetus: RhD positive foetal celss cross the placenta causing anti-D Abs to form 2nd pregnancy: Rhesus +ve foetus: moether is sensitised. Maternal anti-D crosses the placenta and coats foetal RhD +ve cells. Leads to their destruction in spleen and liver

Question 200

What are the clinical features of rhesus disease in foetus

Answer 200

Foetal anaemia and HDFN: anaemia and high bilirubin. Bilirubin accumulates after birth as it is no longer removed by the placenta Hydrops foetalis Kernicterus can result

Question 201

Features of hydrops fetalis

Answer 201

Accumulation of oedema in at least two foetal compartments, can cause spontaneous abortion and heart failure

Question 202

Kernicterus=

Answer 202

Bilirubin induced brain dysfunction

Question 203

What are the methods to prevent rhesus disease

Answer 203

Prevent sensitisation in the first place Anti-D antiglobuline RAADP

Question 204

Prevention of rhesus sensitisation

Answer 204

Transfuse RhD negative childbearing females with RhD negative blood. Give IM injections of anti-D Ig at times when the mother is at risk of fetomaternal bleed

Question 205

What is the timelit for anti-D to be given

Answer 205

72h Doesn't work if previous sensitisation

Question 206

What are the different doses of anti-D used

Answer 206

\<20/40: 250IU \>20/40: 500iU, larger doses are needed for larger bleeds to a FMH/Kleihauer test is conducted to determine the size of the bleed

Question 207

Kleihauer-Betke test

Answer 207

Blood test used to measure the fetal Hb transferred from fetus to maternal blood stream and determine severity of bleed. Acid bath removes adult Hb but not fetal Hb. Staining using Shephard's method appear rose-pink while adult RBC seen as ghosts. Percentage of fetal to maternal cells calculated

Question 208

Answer 208

Kleihauer test, showing fetal red blood cells in rose-pink color, while adult red blood cells are only seen as "ghosts".

Question 209

Dosing for FMH

Answer 209

125iU/mL

Question 210

RAADP

Answer 210

Routine antenatal anti-D prophylaxis for women who are rehsus D negative. 1% of pregnancies have no obvious sensitising event. Routine anti-D prophylaxis is given in 3rd trimester 500iU at 28 and 34w or 1500iU at 30w.

Question 211

Routine management of Abs in pregnancy

Answer 211

Women undergo screen at 11 and 28w to check for RBC Abs If Abs are present, quantify, check and monitor levels. High or rising= more likely to affect the foetus Monitor for HDFN through MCA Doppler USS Deliver baby early as HDN gets worse in last few weeks fo gestation

Question 212

*in utero* Mx of HDFN

Answer 212

Monitor using doppler USS Deliver early Intrauterine transfusions can be given Monitor babies Hb and bilirubin at delivery and for several days after. Transfuse to decrease bilirubin and increase Hb Phototherapy Subsequent pregnancies are usually worse

Question 213

What other antibodies are implicated in HDN?

Answer 213

Anti-C: less severe. Anti-kell: causes reticulocytopenia in foetus as well as haemolysis IgG Anti-A and Anti-B Abs from group O mothers can cause mild HDN but not severe and can be treated with phototherapy

Question 214

What is the difference between forawrd and reverse grouping?

Answer 214

Øuse known anti-A and anti-B and anti-D reagents against patient’s RBCs = FORWARD GROUP Øand A and B reagent RBCs against patient’s plasma (contains IgM antibodies) = REVERSE GROUP

Question 215

Indications for use of platelet as transfusion

Answer 215

Massive transfusion Prevent bleeding post chemo Prevent bleeding post surgery Platelet dysfunction or immune cause

Question 216

What is an adult treatment dose?

Answer 216

One unit of platelets Raises platelet count by 30-40

Question 217

When is a platelet transfusion contraindicated?

Answer 217

Heparin induced TP and TTP

Question 218

Indications for FFP transfusion

Answer 218

Massive transfusion DIC with bleeding Liver disease + Risk Not used to reverse warfarin

Question 219

Draw causes of low plt count

Answer 219

Question 220

Draw ABO blood groups

Answer 220

Question 221

Draw anti-D doses

Answer 221

Question 222

What is SHOT?

Answer 222

Serious hazards of transfusion

Question 223

TRALI=

Answer 223

Transfusion related acute lung injury

Question 224

TACO=

Answer 224

Transfusion associated circulatory overload

Question 225

TAD=

Answer 225

Transfusion associated dyspnoea

Question 226

PTP=

Answer 226

Post-transfusion purpura

Question 227

How can adverse blood transfusion related events be prevented?

Answer 227

Bedside check Use a giving set with a filter in the line Don't add drugs to blood Don't keep blood out of fridge for \>30m without transfusion Do routine obs during hte transfusion

Question 228

Immediate clinical action in SHOT Preventative action

Answer 228

ABC Treat symptoms Check blood components Inform transfusion department Take laboratory sampes Contact local member of tranfusion team Complete incident form Take witness statements Report to SHOT Root cause analysis

Question 229

Features of acute transfusion reaction

Answer 229

May start as rise in temp, pulse or fall in BP Fever, rigors, flushing, vomiting, dyspnoea, pain at transfusion site, loin and chest pain, urticaria, itching, headache, collapse

Question 230

Treatment of acute transfusion reaction

Answer 230

Severe: 2222. Take down components Replace tranfusion with saline to keep the vein open, ABC, haem input Mild: medical assistance, administer antihistamine or paracetamol (diuretics if fluid overload). Observe patient.

Question 231

Features of FNHTR

Answer 231

During or soon after hte transfusion, rise in temp of 1 degree, chills and rigors Slow/stop transfusion Paracetamol Caused by Abs against WBCs, less common with leukodepletion

Question 232

Features of allergic reaction to blood transfusion

Answer 232

Common esp with plasma Mild urticarial or itchy rash, sometimes with a wheeze. During or after transfusion. Stop or slow transfusion Antihistamines Cause: allergen is the donor plasma, so may not recurr dependant on the IgE specificity in the recipient. More common in recipients with hx of atopy

Question 233

What are the most common reactions with RBCs?

Answer 233

Febrile Allergy Unclassified Mixed allergic and febrile Hypotensive Anaphylactic

Question 234

What are the most common ATR with platelets?

Answer 234

Allergic Febrile Anaphylactic Mixed Unclassified Hypotensive

Question 235

What are the most common ATRs with plasma?

Answer 235

Allergic Anaphylactic Febrile Hypotnesive Mixed febrile and hypotensive

Question 236

What are the most common ATRs with mixed components?

Answer 236

Anaphylactic=allergic Febrile=hypotensive Then mixed allergic and febrile

Question 237

Features of Wrong ABO ATR

Answer 237

Sings and symptoms of acute intravascular haemolysis: restlessness, chest/loin pain, fever, vomiting, flushing, collapse, Hburia. Take samples for FBC, biochemistry, coagulation, repeat cross match and DAT. Causes: failure of bedside check, wrongly labelled x-match sample, lab error

Question 238

Features of anaphylaxis ATR

Answer 238

Severe life threatening reaction soon after hte start of the transfusion Patient will be in hypotensive shock, breathless with wheeze and have laryngeal and facial oedema Mech: IgE cross linking with mast cells leading to degranulation. Caused by: previous exposure to Ag and development of an IgE antibodiy. Classically IgA deficiency or IgE Ab is passively transferred by the transfusion

Question 239

What is the differnce between an anaphylactic and an anaphylactoid reaction?

Answer 239

Anaphylactic is IgE mediated

Question 240

Features of IgA deficiency

Answer 240

Partial or total deficiency where anti-IgA Abs are more likely to develop. Can be part of CVID and more commonly associated with infection and autoimmunity. Abs develop in response to sensitising event. At greater risk of allergic transfusion reactions

Question 241

Endogenous infection of blood products Exogenous infection of blood products

Answer 241

Yersinia enterocolitica Salmonella E coli Strep Staphy Pseudomonas Serratia

Question 242

Prevention of bacetial contamination of blood products

Answer 242

R/v blood product Donor questioning Screening of platelets occurs within 36h of donation and are held for further 6h nefore release

Question 243

What is TRALI

Answer 243

Transfusion associated lung injury. Acute dyspnoea with hypoxia and bilateral pulmonary infiltrates during or within 6h of tranfusion

Question 244

Mechanism of TRALI

Answer 244

Donor anti-leucoyte Abs interact with patients WBC Ags which aggregate and stick in pulmonary capillaries Results in release of neutrophil proteolytic enzymes and toxic oxygen metabolites which cause lung damage Prevention is through using male donor plasm and avoiding plasma usage e.g. Warfarin reversal is using vit K.

Question 245

What is TACO

Answer 245

Transfusion associated circulatory overload Occuring within 6h of tranfusion: Acute resp distress Tachycardia Raised BP Acute or worsening pulmonary oedema Evidence of positive fluid balance

Question 246

Causes of TACO

Answer 246

Lack of attention to fluid balance. Can be due to cardiac/renal failure or hypoabluminaemia. Over transfusion

Question 247

What is the impact of 1 unit of RBCs on recipient Hb?

Answer 247

Increases by 1g/dL Check Hb after every 2 units

Question 248

What is TAD?

Answer 248

Tranfusion associated dyspnoea Respiratory distress within 24h of transfusion that does not meet the criteria of TRALI or TACO or allergic reaction.

Question 249

What are the Cxs of massive blood transfusions

Answer 249

e.g. one blood volume in one day? Hypothermia Hyperkalaemia (as stored RBCs leak K) Hypocalacaemia (as anticoagulant in each bag binds to Ca) Air embolism

Question 250

What are the features of delayed haemolytic transfusion reactions?

Answer 250

Lysis of red cells= raised bilirubin, decreased Hb, increased reticulocytes, Hburia over next few days. Can occur to Kidd antigens, anti-D, K, Jk Can cause renal failure May require further transfusions Do DAT

Question 251

What are the intravascular symptoms of haemolytic transfusion reactions? Extravascular?

Answer 251

Red/brown plasma and urine Fall in Hb and jaundice

Question 252

What are some other causes of haemolysis following transfusion?

Answer 252

Bacterial contamination Mechanical damage Addition of drugs incompatibile with IV fluids

Question 253

What viruses are tested for in donor blood?

Answer 253

HBV, HCV, HIV, HTLV but NB window period for infeciton Syphillis CMV (removed through leiukodepletion) Parvovrisu: can affect foetus and patients with haemolytic anaemia

Question 254

What are the features of TA-GvHD

Answer 254

Rare but alway fatal. Donor's blood contains viable lymphocytes that are not recognised by host immune system in susceptible patients. Donor lymphocytes recognise the Ags on patients gut, liver, skin, bone marrow and mount an immunological response Causes severe diarrhoea, liver failure, skin desquamation, bone marrow failure

Question 255

Who is susceptible to TA-GvHD?

Answer 255

Very immunosuppressed: SCT patients, CTx durgs e.g. fludarabine, Hodgkin's foetus. Donor needs to be HLA matched for intrauterine transfusion. (HLA homozygosity)

Question 256

Prevention of TA-GvHD

Answer 256

Identify at risk recipients Irradiate donor blood to leukodeplete

Question 257

Features of PTP

Answer 257

Purpura= pin prick red/purple blood spots due to very low platelets or vasculitis Appears 7-10d post transfusion and can cause life-threatening bleeding. Affects HPA-1a negative patients Usually resolves in 1-4w Sped by IV Ig Need to be given HPA-1a negative platelets

Question 258

Features of Fe overload in transfusions?

Answer 258

Lots of transfusions (\>50) over time can lead to an accumulation of Fe. This can cause organ damage, to hte liver, heart and endocrine system Prevented through the use of Fe chelators e.g. desferioxamine once Fe \>1000g. Used in thalassaemia where patients have monthly transfusions

Question 259

Draw SHOT: immediate and delayed

Answer 259

Question 260

Draw symptoms of ATR

Answer 260

Question 261

Draw fever vs allergic ATR

Answer 261

Question 262

Def: lymphoma

Answer 262

Neoplastic tumour of lymphod tissue Often found in LNs and BM. May spill into blood Sometimes found in other lymphoid tssues e.g. spleen, MALT Rarely found in skin (T-cell), CNS, testes, breast

Question 263

Risk factors for lymphoma

Answer 263

No identifiable risk factor in majority of cases Constant antigenic stimulation, infection and immunosuppression are known to contribute

Question 264

H. pylori and lymphoma

Answer 264

Gastric MALT Lymphoma

Question 265

Sjogren's and lyomha

Answer 265

Parotid lymphoma

Question 266

Coeliac and lymphoma

Answer 266

small bowel T cell lymhoma EATL (enteropathy associated T-cell lymphoma)

Question 267

Viral causes of lyphoma

Answer 267

HTLV1 EBV HIV

Question 268

HTLV1 and lyphoma

Answer 268

Infects T cells by vertical/sexual transmission. May develop adults T-cell leukaemia lymphoma

Question 269

EBV and lymphoma

Answer 269

EBV infects B lymphocytes. Carrier state regulated by healthy T cells. Iatrogenic suppression of T cells e.g. transplantation regimens, leads to increased risk HIV coinfection may also lead to deregulation of EBV infected B cells

Question 270

Why are lymphocytes at risk of malignancy

Answer 270

Prolferative rate Rely on apoptosis: 90% of lymphocytes die, apoptotsis switched off in germinal centre Mutations: DNA undergoes deliberate mutations to generate Ig and TcR diversity.

Question 271

Mutations and Ig in lymphoma

Answer 271

Ig promoter is highly active in B cells, if an intact oncogene is brought close to the Ig promoter, lymphoma may result. NHL mutations: majority are translocations

Question 272

What is the generative tissue in the lymphoreticular system

Answer 272

BM and thymus

Question 273

What is the reactive LR tissue

Answer 273

LNs and spleen: develops immune reaction

Question 274

What is the acquired LR tissue?

Answer 274

Extranodal lymphoid tissue e.g. skin, stomach, lung, to develop local immune reaction

Question 275

LN features

Answer 275

Peripherally B cells Centrally, T cells

Question 276

Function of the B cell area in the LN

Answer 276

Forms a lymphoid follicle. In the mantle zone there are naive unstimulated B lymphocytes In the germinal centre, B cells mix with APC to select them and activate them

Question 277

Diagnosis of lymphoma: Morphology

Answer 277

Cytology Histology

Question 278

Diagnosis of lymphoma: Immunophenotyping

Answer 278

T: CD3 and CD5 B: CD20 Examines cell distribution, loss of surface proteins, abnormal expression of proteins and clonality of B cell

Question 279

Diagnosis of lymphoma: Molecular pattern

Answer 279

FISH: for translocations PCR Diagnostic Prognostic

Question 280

Features of NHL

Answer 280

Most common 80-85% All lymphomas but Hodgkins \>40 subtypes

Question 281

NHL presentation

Answer 281

Varies from subtype to subtype: Painless lymphadenopathy often multilocular Compression symptoms B symptoms **No pain** after ETOH

Question 282

No pain after ETOH

Answer 282

NHL

Question 283

How can NHL e classified

Answer 283

Mature vs immature Histologically: high grade vs low grade Lineage: B or T cell

Question 284

Dx of NHL Staging

Answer 284

Tissue biopsy, WHO subtype CT scan, PET scan (in aggressive lymphomas) BM biopsy LP if risk of CNS

Question 285

What are the prognostic markers in NHL

Answer 285

LDH and performance status

Question 286

What are the high grade aggressive NHLs?

Answer 286

Burkitt's T or B cell lymphoblastic leukaemia/lymphoma Diffuse large B-cell, mantle cell Treated on acute leukaemia protocols

Question 287

What are the low grade indolent lymphomas?

Answer 287

Follicular marginal zone Small lymphocytic MALT

Question 288

Features of Follicular lymphoma

Answer 288

B cell Indolent Mostly incurable: median survival 12-15y t14:18 resulting in overexpression of anti-apoptosis protein Bcl-2 "Follicular pattern" "Nodular appearance"

Question 289

t14:18 resulting in overexpression of anti-apoptosis protein Bcl-2

Answer 289

Follicular lymphoma

Question 290

"Follicular pattern" "Nodular appearance"

Answer 290

Follicular lymphoma

Question 291

Px in follicular lymphoma

Answer 291

Indolent but can transform to a high grade lymphoma

Question 292

Mx of follicular lymphoma

Answer 292

Watch and wait Rixucimab CVP

Question 293

CVP

Answer 293

Cyclophosphamide Vincristine Prednisolone

Question 294

Features of small lymphocytic lymphoma/CLL

Answer 294

Middle aged and elderly found in nodes or blood. Small lymphocytes, naive or post-germinal centre memory B cells. CD5 or 23 Indolent but can transform to high grade lymphoma

Question 295

Featurs of mantle cell lymphoma

Answer 295

Middle-aged, M\>F Aggressive Disseminated at presentation Median survival 3-5y t11:14 translocation. Cyclin D1 deregulation Angular nuclei

Question 296

t11:14 translocation. Cyclin D1 deregulation

Answer 296

Mantle cell lymphoma

Question 297

Angular nuclei

Answer 297

Mantle cell lymphoma

Question 298

Presentation of MALT

Answer 298

May present with dyspepsia or epigastric pain, B symptoms are uncommon

Question 299

Treatment of MALT

Answer 299

Microbial dependent: remove antigen with tirple therapy. Can lead to remission in 75% Microbial independent: CTx

Question 300

Features of MALT

Answer 300

Marginal zone NHL found in middle aged. Chronic antigen syimtulation: H pylori-\> gastric MALT Djogrens-\> Parotid lymphoma

Question 301

What are the types of Burkitt's

Answer 301

Endemic Sporadic Immunodeficiency

Question 302

What is the histology in Burkitt's

Answer 302

Starry sky

Question 303

Features of Burkitt's

Answer 303

Very aggressive Fast growing t8:14 c-myc overexpression, rapidly responsive to Rx

Question 304

Rx in Brukitt's

Answer 304

CTx: Rituximab + leukaemia protocol or SCT

Question 305

Features of endemic Burkitt's

Answer 305

Most common in equatorial Africa EBV associated Characteristic jaw involvement and abdominal masses

Question 306

Features of sporadic Burkitts

Answer 306

Found outside Africa EBV-associated Jaw less commonly involved

Question 307

Features of immunodeficiency Burkitts

Answer 307

Non-EBV associated HIV/post-transplant patients

Question 308

Features of Diffuse Large B cell lymphoma

Answer 308

Middle aged and elderly Aggressive Richter's transformation Other lymphomas occur secondary to DLBCL "sheets of large lymphoid cells, germinal centre or post germinal centre B cells" Germinal centre phenotype is a good prognostic factor

Question 309

"sheets of large lymphoid cells, germinal centre or post germinal centre B cells"

Answer 309

DLBC

Question 310

What are the components of the international prognostic indec for lymphoma?

Answer 310

Age \>60 Serum LDH \>normal Performance status 2-4 Stage III-IV More than one extranodal site

Question 311

Rx of DLBC

Answer 311

Rituximab-CHOP Auto-SCT for relapse

Question 312

R-CHOP?

Answer 312

R- Rituximab: anti CD20 monoclonal antibody anti-B cell Cyclophosphamide Adriamycin Vincristine Prednisolone

Question 313

MOA Rituximab

Answer 313

Anti CD20: anti B cell

Question 314

Features of peripheral T-cell lymphoma

Answer 314

Middle aged and elderly Aggressive Large T cells with associated reactive cell population, especially eosinophils

Question 315

Large T cells with associated reactive cell population, especially eosinophils

Answer 315

Peripheral T cell lymphoma

Question 316

Features of adult T cell leukaemia/lymphoma

Answer 316

Carribean and Japan Associated with HTLV-1 infection

Question 317

Features of EATL

Answer 317

Associated with longstanding coeliac

Question 318

Features of cutaenous T cell lymphoma

Answer 318

Associated with mycosis fungoides

Question 319

Features of anaplastic large cell lymhpoma

Answer 319

Children and young adults Aggressive Large epitheloid lymphocytes t2:5 Alk-1 protein expression (+ve= better Px)

Question 320

Large epitheloid lymphocytes

Answer 320

Anaplastic large cell lymphoma

Question 321

t2:5 Alk-1 protein expression (+ve= better Px)

Answer 321

Anaplastic large cell lymphoma

Question 322

Reed-sternberg cell=

Answer 322

Hodgkins

Question 323

binucleate/multinucleate owl-eyed cell on background of lyphomcytes and reactive cells=

Answer 323

Reed-Sternberg= HL

Question 324

Answer 324

Reed-Sternberg cell

Question 325

Clinical presentation of HL

Answer 325

Asymmetrical painless lymphadenopathy +/- obstructive/mass effect symptoms Mediastinal mass, cough, respiratory infectoin, SVCO, dysphagia Constitutional symptoms (incl pruritus)

Question 326

Alcohol induced pain (rarely)

Answer 326

HL

Question 327

Pel-Ebstein fever

Answer 327

Cyclical 1-2 weekly fever seen in HL

Question 328

Epidemiology of HL

Answer 328

M\>F Bimodal age incidence: 20-29 and \>60

Question 329

Most common type of HL?

Answer 329

Nodular sclerosing, good Px causing peak incidence in young women

Question 330

Ix in HL

Answer 330

CT/PET Tissue dx: LN or BM biopsy, cell stain with CD15 and CD30 Reed-sternberg cell on a background of lymphocytes and reactive cells

Question 331

Features of classical HL

Answer 331

Young and middle aged, often involving single LN and supradiaphragmatic Thought to be germinal/post-germinal centre in origin EBV and HLA DPB1 associated Reed-Sternberg and Hodgkins cells

Question 332

Richter's transformation

Answer 332

Richter's syndrome (RS), also known as Richter's transformation, is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL)[1] and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis.[2]There is also a less common variant in which the CLL changes into a Hodgkin's lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis. [3]Richter's transformation affects about 5% of CLL patients at some point during their lives.[4]

Question 333

EBV associated and HLA DPB1

Answer 333

Classical HL

Question 334

Features of nodular lymphocyte predominant HL (NLPDHL)

Answer 334

Isolated lymphadenopathy Germinal centre B cell No EBV association B cell richnodules with scattered L and H cells. Can transform to high grade B cell lymhpoma

Question 335

Staging of HL

Answer 335

1: one LN region (including spleen) 2: \>2 LN regions on the same side of the diagram 3: \>2 LN regions on different side of the diagram 4: Extranodal sites: BM, liver A: no constitutional symptoms B: constitutional symptoms

Question 336

Mx of Hodgkins

Answer 336

Combination CTx used in most cases RTx often used alongside CTx in large areas. Intensive CTx and autologous SCT: relapsed patients

Question 337

ABVD

Answer 337

Used in HL Adriamycin Bleomycin Vinblastine Decarbazine Given at 4 weekly intervals

Question 338

What are the issues for treating HL

Answer 338

Combination CTx and RTx increases the risk of secondary C

Question 339

Features of Autologous SCT

Answer 339

Patients own SCs Enbales high dose CTx and RTx to eradicate malignant cells Frozen SCs then reintroduced into ptient Used in MM and lymhpoma more than leukaemia No risk of GvHD

Question 340

Features of allogenic SCT

Answer 340

HLA-matched donor SCs are harvested Patients own BM completely eradicated Donors SCs are introducted Used more in leukaemia GvHD, risk of opprotunistic infections, infertility and secondary malignancies

Question 341

Lymphoma tree

Answer 341

Question 342

Draw NHL and the LN

Answer 342

Question 343

Draw normal haematopoeisis

Answer 343

Question 344

Draw the hierarchy of haematological malignancies

Answer 344

Question 345

What are the myeloid malignancies?

Answer 345

AML (\>20%) Acute promyelocytic (like AML but more mature cells) Myelodysplasia Myeloproliferative CML (mature cells)

Question 346

What are the lymphoid malignancies?

Answer 346

Precursor cell: ALL Mature cell: CLL MM NHL and HL

Question 347

What are type 1 mutations in haematological malignancies

Answer 347

Involved in cellular proliferation e.g. RtK Activation of TK leads to expression in mature cells RBCs: PCV Platelets: thrombocytopenia Granulocytes: CML

Question 348

What is the BCR-ABL mutation seen in? What type of mutation

Answer 348

CML Type 1

Question 349

What are type 2 mutations?

Answer 349

Prevent differentiation Translocations create fusion genes

Question 350

What is AML-ETO seen in? What type of mutation?A

Answer 350

AML Type 2

Question 351

What is PML-RARA seen in? What type of mutation?

Answer 351

APML Type 2

Question 352

What is t9:22

Answer 352

Philadelphia chromosome Seen in CML

Question 353

What is BCR-ABL

Answer 353

Fusion gene created in CML. Philadelphia chromosome

Question 354

What is the philadelphia chromosome?

Answer 354

Mutation affecting GM-CSF causing proliferation of the granulocytes Caused by activating tyrosine kinase mutation Large numbers of differentiated neutrophils are present in the peripheral blood

Question 355

Large numbers of differentiated neutrophils in peripheral blood with an increase in myelocytes and increased platelets

Answer 355

CML

Question 356

Epidemiology of CML

Answer 356

M:F 1.4:1 40-60y/o

Question 357

Symptoms of CML

Answer 357

Weight loss, lethargy, night sweats, splenomegaly, anaemia, bursing, bleeding and gout Splenomegaly due to infiltration of cords and red pulp by granulocytes, if massive, infarction may occur

Question 358

What are the phases of CML?

Answer 358

Bi or triphasic Chronic phase: 5-6y stabilisation. 80% diagnosed here. \<5% of cells in blood are blast cells. Leucocytosis 500-5000 myeloid cells. Neutrophils and myelocytes no excess of myeloblasts Bone marrow very hypercellular due to increased numbers of neutrophils and their precurorors Accelerated phase: 6-12m. 10-19% of peripheral cells are blast cells Blast crisis: 3-6m surivival. \>20% blast cells.

Question 359

Answer 359

Leucocytosis with mature myeloid cells CML

Question 360

Monitoring of CML

Answer 360

FBC and leucocyte count Cytogenetics: philadelphia chromosome. RT-PCR of the ABL-BCR fusion transcript. Haematological resposne: complete CHR WBC \<10 Cytogenetic response: 0% philadelphia positive Molecular: reduction in BCR-ABL transcripts. Molecular most sensitive

Question 361

Treament of CML

Answer 361

Need to target activated RtK: ABL kinase inhibitor

Question 362

First line Rx in CML

Answer 362

RtK: Imatinib 93% survival at 60m

Question 363

Second line Rx in CML

Answer 363

RtKI: dasatanib and nilotinib

Question 364

Management of failure in CML

Answer 364

Monitor BCR-ABL transcripts, if rising some may respond to 2nd gen. Failure of TKIs consider allogenic SCT (good survival in CP, extremely poor in blast crisis)

Question 365

Pathogenesis of AML

Answer 365

Two hit model T8:21 mutation resulting in AML-ETO fusion protein. This is a tumour suprresor known as p14ARF

Question 366

T8:21 mutation

Answer 366

AML

Question 367

Management of AML

Answer 367

Supportive:red cell transfusions, platelet transfusions. Nurse in isolation, prompt antiboitcs.

Question 368

Dx of AML

Answer 368

Morphology Immunophenotyping: lineage and stage of differentation. Examine expression of antigens on cell surface. Cytogenetics: chromosomal translocations Molecular genetics: detection of fusion mRNA

Question 369

Def: Acute Leukaemia

Answer 369

A neoplastic condition characterised by rapid onset, early death if untreated, immature blast cells and BM failure

Question 370

What lineage of cells is affected in AML

Answer 370

Pluripotenet HSC or granulocyte/monocyte precursor

Question 371

What lineage of cells is affected in CML

Answer 371

Pluripotent HSC

Question 372

What lineage of cells is affected in B-ALL

Answer 372

B cell

Question 373

What lineage of cells is affected in T-ALL

Answer 373

T cells

Question 374

What lineage of cells is affected in CLL

Answer 374

Terminal B cell

Question 375

Haematological definition of acute leukaemia

Answer 375

Immature blasts \>20% BM cells

Question 376

What are the clinical features of acute leukaemia

Answer 376

BM function failure: anaemia, thrombocytopenia, neutropenia Organ infiltration: hepatomegaly, splenomegaly, lymphadenopathy, bone pain, CNS, skin, gum hypertrophy

Question 377

Aetiology of acute leukaemia

Answer 377

Uinknown Ionising radiotherapy Cytotoxic drugs Benzene Pre-leukaemic disordres: myelodsplastic syndrome DS: AML++ Neonates: often develop transient abnormal myelopoeisis

Question 378

Which population group is affected by ALL?

Answer 378

Children Children get it ALL

Question 379

Which population group is affected by AML

Answer 379

Adulthood: risk increases with age Infants \<2

Question 380

What are the clinical features of ALL

Answer 380

As for leukaemia but Lymphadenopathy ++++ CNS involvement ++++ Testicular enlargement Thymic enlargement

Question 381

What are the clinical features of AML

Answer 381

As for leukaemia but Lymphadenopathy less common.

Question 382

What is acute promyelocytic anaemia?

Answer 382

Medical emergency Prone to DIC

Question 383

Ix in ALL

Answer 383

High WCC Lymphocytes/precursors +++

Question 384

Ix in AML

Answer 384

High WCC Auer rods and granules Myeloperoxidase and Sudan Black B stains

Question 385

Auer rods

Answer 385

AML

Question 386

T15:17 associated with

Answer 386

Acute promyelocytic leukaemia. Increased risk of DIC

Question 387

What is classical AML

Answer 387

T15:17

Question 388

Clinical features of Acute Monocytic leukaemia

Answer 388

CNS disease, skin infiltration, gum infiltration, organomegaly.

Question 389

What is an issue with very high WCC?

Answer 389

Hyperviscosity.

Question 390

What has a good prognosis in AML?

Answer 390

T15:!7 T 8:21 Intermediate and poor risk have normal/complex karyotypes and other chromosomal abnormalities

Question 391

Treatment of AML

Answer 391

Supportive: RBC, platelest, FFP if DIC, antibiotics, long line. Allopurinol, U&Es monitoinrg CTx: Danorubicin and cytarabine. Combination therapy, non-overlapping toxicity with synergistic effect. 4-5 courses. remission induced in 2 courses and consolidated in 2-3 courses. Allo-SCT in young or if poor prognosis.

Question 392

CTx in AML

Answer 392

Daunorubicin and cytarabine 4-5 courses Remission induction in first 2 Consolidation in 2-3 courses

Question 393

When is the Px of ALL worse?

Answer 393

With increasing age

Question 394

What are the features of B lineage ALL

Answer 394

Starts in bonw marrow, very strong association between genetics and prognosis Poor prognosis associated with philadelphia chromosome

Question 395

What are the features of T cells lineage ALL

Answer 395

Starts in thymus which amy become enlarged.

Question 396

Treatment of ALL

Answer 396

(Ph +ve need imatinib) Systemic chemotherapy and CNS directed therapy Lasts 2-3 yeasr Remission induction cycle Consolidation and CNS therapy: intrathecal Ctx to treat occult CNS disease for 6-8 treatments. If lymphoblasts in CSF then more frequent and intesnive therapy required. Intensification Maintenance therapy Consider allogenic SCT Supportive: Blood products, Abx, allopurinol, fluids, electrolytes (to prevent tumour lysis syndrome). May require leukapharesis if extreme leukocytosis

Question 397

CTx treatment of ALL

Answer 397

Systemic CTx and CNS directed therapy lasting 2-3 yeasrs with intrathecal CTx to treat occult CNS disease for 6-8 treatments.

Question 398

Case 1: 5 yr boy. WCC 180 x 109/L, Hb 93 g/L, platelet 43 x 109/L. Thymic mass

Answer 398

WCC : diagnosis of leukaemia most likely. o Low Hb and platelet – bone marrow infiltration. Thymic mass: infiltration by T lymphoblasts.

Question 399

Pathophysiology of Megaloblastic anaemia

Answer 399

DNA cannot be produced fast enought to allow cell division at the right time resulting in larger RBCs e.g. folate and B12 deficiency. Associated with bone marrow features like meagloblasts, ovalocytes in the peripheral blood and hypersegmented neutrophils

Question 400

Answer 400

Megaloblastic anaemia

Question 401

What results in the production of codocytes/target cells?

Answer 401

Pathologies of the liber spleen which result in increased red cell membrane

Question 402

What are the mechanisms of macrocytic anaemia

Answer 402

Megaloblastic anaemia Red cell membrane disorders Alcohol Rapid cell turnover and reticulocytosis

Question 403

Features of macrocytic anaemia caused by rapid red celll turnober and reticulocytosis

Answer 403

Diseases in which there is a high red cell production causes a greater proportion of reticulocytes (which are larger) e.g. COPD: low O2 levels induces production, traumatic loss, rapid haemolysis (G6PDD)

Question 404

Normal RBC lifespan

Answer 404

120d

Question 405

What is haemolysis?

Answer 405

Shortened red cell survival

Question 406

Draw the classiciation of haemolytic anaemias

Answer 406

Question 407

Causes of intravascular haemolysis

Answer 407

Malaria G6PD Mismatch Cold Ab haemolytic syndromes Drugs MAHA: HUS, TTP, PNH

Question 408

What are the MAHAs?

Answer 408

HUS, TTP, PNH

Question 409

What are the extravascular causes of HA?

Answer 409

Autoimmune, alloimmune, hereditary and spherocytosis

Question 410

What are the inherited causes of HA?

Answer 410

Membrane: cytoskeletal proteins, cation permeability Red cell metabolism Hb: thalassaemia, SCD, unstable Hb variants

Question 411

What are the consequences of HA?

Answer 411

Anaemia Erythroid hyperplasia with increased rate of RBC production and reticulocytes Increased folate demand Susceptibility to Parvovirus B19 Cholelithiasis: increased risk if inherited with Gilbert Increased risk of Fe overload and osteoporosis Fe overload can lead to hepatic siderosis

Question 412

What is hepatic siderosis

Answer 412

Hemosiderosis (AmE) or haemosiderosis(BrE) is a form of iron overload disorderresulting in the accumulation ofhemosiderin. Types include: Transfusion hemosiderosis[1] Idiopathic pulmonary hemosiderosis Transfusional diabetes[2][3] Hemosiderin deposition in the lungs is often seen after diffuse alveolar hemorrhage, which occurs in diseases such asGoodpasture's syndrome, granulomatosis with polyangiitis, and idiopathic pulmonary hemosiderosis. Mitral stenosis can also lead to pulmonary hemosiderosis. Hemosiderin collects throughout the body inhemochromatosis. Hemosiderin deposition in the liver is a common feature of hemochromatosis and is the cause of liver failure in the disease. Selective iron deposition in the beta cells of pancreatic islets leads to diabetes[1] [2] due to distribution of transferrin receptor on the beta cells of islets [3] and in the skin leads to hyperpigmentation. Hemosiderin deposition in the brain is seen after bleeds from any source, including chronic subdural hemorrhage, Cerebral arteriovenous malformations,cavernous hemangiomata. Hemosiderin collects in the skin and is slowly removed after bruising; hemosiderin may remain in some conditions such as stasis dermatitis. Hemosiderin in the kidneys has been associated with marked hemolysis and a rare blood disorder called paroxysmal nocturnal hemoglobinuria. Hemosiderin may deposit in diseases associated with iron overload. These diseases are typically diseases in which chronic blood loss requires frequent blood transfusions, such as sickle cell anemia and thalassemia, though beta thalassemia minor has been associated with hemosiderin deposits in the liver in those with non-alcoholic fatty liver disease independent of any transfusions.[4][5]

Question 413

Consequences of all haemolytic anaemias

Answer 413

Rasised (unconjugated) bilirubin Raised urobilinogen Raised LDH Reticuylocytosis (raised MCV and polychromasia) May have gallstone

Question 414

Consequences of intravascular HA

Answer 414

Raised free plasma Hp Decreased haptoglobins (bind Hb) Hburia dark red urine Methaemalbuminaemia (Hb and albumin in blood)

Question 415

Consequences of extravascular HA

Answer 415

Splenomegaly

Question 416

Clinical features of HA

Answer 416

Pallor, jaundice, splenomegaly, pigmenturia, Fhx

Question 417

What are the inherited membrane defects causing HA

Answer 417

Hereditary spherocytosis Hereditary elliptocytosis Southe East Asian Ovalocytosis Hereditray pyropoikilocytosis

Question 418

What is the inheritance pattern of HS?

Answer 418

AD

Question 419

What are the features of hereditary spherocytosis

Answer 419

Ankyrin or spectrrin deficiency Mechanical abnromality acoompanied by osmotic changes Susceptibility to parvovirus B19 and develop gallstones Extravascular haemolysis: splenomegaly. Spherocytes, increased osmotic fragility, -ve DAT, flow cytometry

Question 420

Spherocytes, increased osmotic fragility, -ve DAT, flow cytometry

Answer 420

Hereditary spherocytosis

Question 421

Why does hereditary spherocytosis cause splenomegaly?

Answer 421

Beacuse it is extravascular HA

Question 422

What is the osmotic fragility test

Answer 422

Hypotonic saline-\> lysis.

Question 423

Answer 423

Hereditary spherocytosis

Question 424

Treatment of hereditary spherocytosis

Answer 424

Splenectomy Folic acid

Question 425

What does a negative Coomb's test tell you?

Answer 425

That the HA is not immune mediated

Question 426

What interactions are disrupted in spherocytosis?

Answer 426

Vertical interactions.

Question 427

What is the most common cause of hereditary spherocytosis

Answer 427

Mutation in Ankyrin

Question 428

What population commonly affected by HS?

Answer 428

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry

Question 429

Minkowski–Chauffard syndrome

Answer 429

Hereditary spherocytosis

Question 430

Reduced binding of dye eosin-5-maleimide?

Answer 430

Hereditary spherocytosis

Question 431

Inheritance of elliptocytosis

Answer 431

AD

Question 432

What is the msot common cause of hereditary ellliptocytosis?

Answer 432

Spectrin mutaiton (alpha)

Question 433

What are the features of hereditrary elliptocytosis?

Answer 433

Mechanical dysfunction without osmot changes Severity of disease ranges from hydrops foetalis to asymptomatic Disruption of horixontal interactions

Question 434

What is the inheritance of hereditary pyropoikilocytosis?

Answer 434

AR

Question 435

What are the features of hereditrary pyropoikilocytosis?

Answer 435

AR Abnormal sensitivity to heat causing haemolysis Considered a special form of elliptocytosis

Question 436

Answer 436

Hereditary elliptocytosis

Question 437

Answer 437

Hereditary pyropoikilocytosis

Question 438

Answer 438

SEA Ovalocytosis

Question 439

What are the features of SEA ovalocytosis?

Answer 439

Form of hereditary elliptocytosis most common in Malaysia and papau new guinea. Confers some protection to M. falciparum Macro-ovalocytes with one or two slits in 20-50% of the cells. Heterozygotes asymptomatic, homozygosity presumed lethal

Question 440

What is the commonest RBC enzyme defect?

Answer 440

G6PD

Question 441

What are the features of G6PDD

Answer 441

Prevalent in areas of malarial endemicity Most common RBC enzyme defect- X linked. Attacks: rapid anaemia and jaundice with bite cells and Heinz bodies (blue deposit= oxidised Hb)

Question 442

What is the function of G6PD

Answer 442

G6PD catalyses the first step in the pentose phosphate pathway which generates NADPH which is required to maintain intracellular glutathione. GSH is an antioxidant and protexts cellular components

Question 443

What are the clinical effects of G6PDD

Answer 443

Neonatal jaundice Acute haemolysis (triggered by oxidants/infection) Chronic haemolyic anaemia

Question 444

What is the clinical course of G6pD?

Answer 444

Steady state is asymptomatic Acute haemolysis occurs due to oxidant stress

Question 445

What type of HA is G6PD?

Answer 445

Intravascular

Question 446

What factors may precipitate HA attack in G6PD?

Answer 446

Drugs: primaquine (antimalarial), sulphonamides, ciprofloxacin, nitrofurantoin (antibiotics), other drugs: dapsone, Vit K. Broad beans (fava beans), moth balls). Acute stressors e.g. infection

Question 447

Treatment of G6PD

Answer 447

Avoid precipitants Transfuse if severe Genetic subtypes give chronic haemolysis for which splenectomy is a good treatment

Question 448

Heinz bodies

Answer 448

Seen when stained with methylene blue. Formed by Hb damage by oxidants G6PD

Question 449

What population commonly affected by G6PDD?

Answer 449

African, mediterranean, middle eastern

Question 450

What is the inheritance of pyruvate kinase deficiency?

Answer 450

Autosomal recessive but AD has been observed

Question 451

What is pyruvate kinase?

Answer 451

Most common enzyme deficiency of the glycolytic pathway.

Question 452

What are the cliniical features of pyruvate kianse deficiency

Answer 452

HA of varying severity Can cause severe neonatal jaundice and splneomegaly

Question 453

Pathophysiological of pyruvate kinase deficiency

Answer 453

ATP depltion Loss of K through lack of ATP impairing Na/K ATPase and loss of H2O Dehydrated and rigid cells and destruction of poorly deformable cells. Spleenctomy to treat

Question 454

Mx of HAs?

Answer 454

Folic acid supplementaitons Avodi precipitating factors RBC transfusion/exchange Immunisation against BBV Monitor for chronic cxs Cholecystectomy for symptomatic gallstones Splenectomy if indicated

Question 455

What are the indications for splenectomy in HA?

Answer 455

PK deficiency and some other enzymopathies HS Severe elliptocytosis and pyropoikilocytosis, thalassaemia, immune HA Also if transfusion dependant, grwoth delay, physical limitaiton, Hb \<8, hypersplenism Don't do under 3y/o but do before 10y/o to maximise prepubertal growth. Risk of overwhelming sepsis

Question 456

Features of SCD

Answer 456

AR Single base mutaiton; GAG-GTG. Glu-\> Val at codon 6 on beta chain. Leads to HbS instead of HbA

Question 457

What is the pathophysiology of HbS?

Answer 457

GAG-\>GTG Glu-Val at codon 6 of beta chain

Question 458

Which Hb chain does SCD affect?

Answer 458

beta

Question 459

What are the possible genotypes and their phenotypes in SCD

Answer 459

HbSS: severe HbAS: sickle cell trait, usually asymptomatic. Rarer forms: HbSC: Sickle cell HbC disease.(HbC has defective beta chain) HbS/beta: Sickle Beta thalassaemia.

Question 460

Why does sickle cell anaemia manifest at 3-6m?

Answer 460

Coincides with decreasing fetal Hb (HbF)

Question 461

What is the pathophysiological mechanism for sickling?

Answer 461

Reduced O2 tension leads to HbS polymerisation and subsequent sickling

Question 462

What are the important features of SCA?

Answer 462

Anaemia 60-80g/L Splenomegaly Foalte deficiency Gallstones Aplastic crises (parvovirus B19)

Question 463

What are the vaso-occlusive features of Sickle-cell disease? SICKLED

Answer 463

Stroke Infections (hyposplenism, CKD) Crises Kidney: papillary necrosis, nephrotic syndrome Liver: gallstones Eyes: retinopathy Dactilitis: impaired growth Mesenteric iscahemic Priapism

Question 464

What are the clinical features of a sickle cell crisis?

Answer 464

Splenic sequestration Chest and pain

Question 465

How does the age of onset of SCD affect px

Answer 465

Child: strokes, splenomegaly, splenic crises and dactylitis. Teens: impaired growth, gallstones, psych, priapism Adult: hyposplenism, CKD, retinopathy, pulmonary HTN

Question 466

Dx of SCD

Answer 466

Sickle cells and target cells on blood film Sickle solubility test Hb electrophoreisis Guthrie to test to aid prompt pneuomococcal prophylaxis

Question 467

Treatment of sickle cell disease

Answer 467

Analgesia for painful crises Folic ACid Penicllin V Pneumovax HiB vaccine Hydroxycarbamide Carotid doppler monitoring in early childhood with prophlyactic exchange transfusion if turbulent carotid flow

Question 468

Mechanism of hydroxycarbamide in SCD

Answer 468

Promotes production of HbF

Question 469

What is the pathology of thalassaemias?

Answer 469

Unbalanced Hb synthesis-\> unmatched globins precipitate-\> haemolysis and ineffective erythropoeisis

Question 470

What are the features of beta thalassaemia?

Answer 470

Point mutations leading to reduced beta chain synthesis, excess alpha cahins Raised HbA2 and HbF

Question 471

What are the signs of beta-thalassaemia?

Answer 471

Skull bossing, maxillary hypertrophy, hairs on end skull XR

Question 472

Answer 472

In severely affected patients, a widening of the diploic space (medulla) with a thinning of the tables (cortices) occurs, frequently with complete obliteration of the outer table. New bone forms in response to marrow proliferation beneath the periosteum. These bony spicules may be seen radiographically and result in a classic "hair-on-end" appearance. Because it lacks hematopoietic marrow, the occipital bone usually is not involved. (See the image below.)

Question 473

What are the different types of beta thalassaemia?

Answer 473

Minor Intermedia Major

Question 474

What are the features of beta thalassaemia minor

Answer 474

Heteroztgous Asmptomatic carrier Mild anaemia

Question 475

What are the features of beta thalassaemia intermedia?

Answer 475

Moderate anaemia Splenomegaly Bony deformity Gallstones

Question 476

What are the features of beta thalassaemia major

Answer 476

Homoxygous 3-6m severe anaemia FTT Hepatosplenomegaly Bony deformity Severe anaemia Heart failure

Question 477

Mx of beta thalassaemia

Answer 477

Blood transfusions Desferrioxamine Folic acid

Question 478

Features of alpha thalasasaemia

Answer 478

Deletions in alpha chain of Hb: reduced synthesis and excess beta chains Therea re 4 alpha genes, severity depends on number of genes deleted

Question 479

A thalassaemia trait

Answer 479

1/2 alpha genes deleted Asymptomatic/ mild anaemia

Question 480

HbH

Answer 480

3 alpha chains deleted Moderate anaemia Splenomegaly

Question 481

4 alpha chains deleted

Answer 481

Hydrops foetalis- incompatibble with life

Question 482

What are the two tpyes of autoimmune HAs?

Answer 482

Warm and Cold

Question 483

What is the most common AIHA?

Answer 483

Warm

Question 484

What are the features of WAIHA?

Answer 484

37 degress **IgG** Positive Coomb's Spherocytes on blood film

Question 485

What Ig is associated with WAIHA?

Answer 485

IgG

Question 486

What are the features of cold agglutinin disease?

Answer 486

\<37 IgM Positive Coomb's Associated with Raynaud's

Question 487

What Ig in cold agglutinin disease?

Answer 487

IgM

Question 488

What are the causes of WAIHA

Answer 488

Mainly idiopathic Lymphoma, CLL, SLE, methyldopa

Question 489

Mx of WAIHA?

Answer 489

Steroids Splenectomy Immunosuppression

Question 490

Mx of cold agglutinin disease?

Answer 490

Treat underlying condition Avoid the cold Chlorambucil

Question 491

What is PCH?

Answer 491

Paroxysmal cold haemoglobinuria

Question 492

What are the features of PCH?

Answer 492

Hb in the urine usually caused by a viral infection e.g. measles, syphillis, VZV Donath-Landsteiner Abs-\> stick to RBCs in cold, lead to complement mediated haemolysis on reqarming.

Question 493

Donath-Landsteiner Abs seen in?

Answer 493

Paroxysmal cold haemoglobinuria

Question 494

What are the features of PNH

Answer 494

Acquired loss of protective surface GPI markers on RBCs (platelets and neutrophil) leads to complement mediated lysis. This results in a chronic intravascular haemolysis, especially at night.

Question 495

What are the symptoms of PNH

Answer 495

Morning haemoglobinuria Thrombosis (+ Budd Chiari syndrome)

Question 496

Dx of PNH

Answer 496

Immunophenotype shows altered GPI or Ham's test

Question 497

What is Ham's test?

Answer 497

In vitro acid induced lysis Seen in PNH

Question 498

What is the treatment of PNH?

Answer 498

Iron/folate supplements Prophlyactic vaccines/antibodies Monocloncal abs e.g. eculizumab that prevents complement from binding RBCs

Question 499

What is the pathology of MAHA

Answer 499

Mechanical RBC destruction: forcedthrough fibrin/plt mesh in damaged vessels leading to schisotcytes

Question 500

Schistocytes= Seen in?

Answer 500

RBC fragments MAHA

Question 501

What are the causes of MAHA

Answer 501

HUS TTP DIC Pre-ecl

Question 502

Rx in MAHA

Answer 502

PLEX

Question 503

What is the pentad of TTP?

Answer 503

MAHA Renal impairment Fever Neurological abnromalities Thrombocytopenia

Question 504

What are the features of HUS

Answer 504

Caused by E coli Toxin damages endothelial cells-\> MAHA Diarrhoea Renal failure No neuro problems Affects children and elderly

Question 505

What is the commonest leukaemia in te western world?

Answer 505

B Cell CLL

Question 506

Def: B Cell CLL

Answer 506

Proliferation of mature non-functioning B lymphocytes

Question 507

Epidoemiology of CLL

Answer 507

Caucasian and black population 20-30x more than Inidian, China, Japan 65-70y/o 40% of all leukaemias in people over 65 1/3rd \>?75, 1/3rd\< 65 1/3rd in between

Question 508

Natural history of CLL

Answer 508

Progressive accumulation of mature malignant B lymphocyts Takes decades and may be a coincidental laboratory finding although can also present acutely

Question 509

What are the clinical issues with CLL

Answer 509

Proliferation in BM-\> failure Circulation in the nodes and spleen-\> lymphadenopathy Acquisition of further mutations can lead to a transformation to a high grade lymphoma Can lead to autoimmune problems e.g. HA

Question 510

Where is CLL primarily seen?

Answer 510

BM

Question 511

Where is Small lymphocytic lymphoma seen?

Answer 511

LNs

Question 512

Clinical presentation of CLL

Answer 512

Incidental finding in routine bloods (80%) Symmetrical painless lymphadenopathy Splenomegaly BM failure: anaemia & thrombocytopenia, recurrent infections B symptoms: fevers, night sweats, weight loss Associated with autoimmunity: AIHA, ITP Can progress to a form of lymphoma (DLBC)- Richter's transformation

Question 513

What is Richter's transformation?

Answer 513

Richter's syndrome (RS), also known as Richter's transformation, is atransformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL) and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad Px

Question 514

Ix in CLL

Answer 514

WCC: persistent lymphocytosis \>5: morphology, immunophenotyping, cytogenetics. Composed of small mature lymphocytes Low serum Ig Smear cells seen on blood film Abnormal BM: lymphocytic replacement of normal marrow May also find immuneparesis and paraptroteins

Question 515

Smear cell

Answer 515

CLL

Question 516

Answer 516

CLL Smear cell are cells that are damaged due to peripheral blood smear Due to reduced strength of abnormal white cells in CLL

Question 517

Dx of CLL

Answer 517

Dx: small mature lymphocytes with smear cells Immunophenotyping Dx: lymphocytosis \>5, smear cells, immunophenotyping: CD5 positive, CLL score

Question 518

DDx of CLL

Answer 518

CLL/SLL Mantle cell lymphoma

Question 519

Good prognositc factors in CLL

Answer 519

Hypermutated IgG Low Zap-70 expression 13q14 deletion

Question 520

Bad prognostic factors in CLL

Answer 520

Raised LDH CD38+ve 11q23 del

Question 521

Px of CLL

Answer 521

50% of patients die of an unreleated cause Incurable by CTx No benefit to early treatment

Question 522

How can CLL be staged?

Answer 522

Binet and Rai Staging

Question 523

How is CLL stgaed using Binet

Answer 523

A B C

Question 524

Binet A

Answer 524

\<3 lymphoid areas

Question 525

Binet B

Answer 525

\>3 lymphoid areas

Question 526

Binet C

Answer 526

Hb \<10 Plt \<100

Question 527

How is CLL staged using Rai staging

Answer 527

0 - IV

Question 528

Rai Stage 0

Answer 528

Lymphocytosis only Low risk

Question 529

Rai Stage I

Answer 529

Lymphadenopathy

Question 530

Rai Stage II

Answer 530

Intermediate risk Hepatosplenomegaly +/- lymphadenopathy

Question 531

Rai Stage III

Answer 531

High Risk Hb \<11

Question 532

Rai Stage IV

Answer 532

plt \<100

Question 533

ZAP70/CD38

Answer 533

Detected in CLL by immunophenotyping Expression correlates with Ig status. Bad prognostic feature

Question 534

What is the worst prognositc facture in cytogenetics for CLL?

Answer 534

-17p (p53)

Question 535

Rx in CLL

Answer 535

Supportive treatment Treatment of complications: immune haemolysis, disease transformation CTx: Stage A: conventional not to treat. Indications for treatment include BM failure, major or progressive lymphadenoapthy, progressive lymphocytosis, systemic symptoms, autoimmune cytopenias

Question 536

CTx in CLL

Answer 536

First line: FCR (fludarbine, cyclophosphamide, rituxmiab) Oral chlorambucil for slow goa nd no go 17p needs different therapy 2nd line for \<60y: consider allograft

Question 537

What is used for p53 mutated CLL

Answer 537

Campath/alemtuzumab

Question 538

Auotimmune complications of CLL

Answer 538

AIHA Autoimmune thrombocytopenia Neutropenia Pure red cell aplsia Mx with steroids

Question 539

PRCA

Answer 539

Pure red cell aplasia (PRCA) orerythroblastopenia refers to a type ofanemia affecting the precursors to red blood cells but not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells.

Question 540

Mx of high grade transformation in CLL

Answer 540

LN biopsy CHOP-R

Question 541

Mx of infection risk in CLL

Answer 541

Prophylaxis and treatment of infection Antibiotics PCP rpophylaxis for those eceiving FDA or campath IvIG for those with hypogammaglobulinaemia Pneumovax and HiB

Question 542

Def: myelodysplastic syndromes

Answer 542

Biologically heterogeneous group of acquired HSCT disorders Characterised by: the development of aclone of marrow stem cells with abnromal maturation resulting in: functionally defective blood cells and numerical reduction Cytopenias Functional abnromaltieies of erythroid, myeloid and megakaryocyte maturation Increased risk of transformation to AML Typically a disorder of the elderly

Question 543

Blasts in myelodysplastic syndromes?

Answer 543

\<20 If it were greater than \>20 it would be a leukaemia

Question 544

Clinical features of MDS?

Answer 544

Bm failure and cytopenias: infection, bleeding, fatigue Hypercellular BM Defective cells: RBC: ring sederoblasts WBC: hyogranulationn, pseudo Pelget Huet anomaly PLatelets: micromegakaryotcytes, hyoablated nuclei

Question 545

What is Pelger-Huet anomaly

Answer 545

Neutrophil with bilobed Pelgroid nuclei. Look identical to those seen in the inherited Pelger-Huet anomaly. Neutrophil has markedly reduced granulation.

Question 546

Answer 546

Pelger-Huet Anomaly Abnormality in neutrophils seen in MDS

Question 547

What are the abnormal bone marrow morphologies seen in MDS

Answer 547

Pelger Huet abnromaltiy Dysgranulopoeisis of neutrophils Myelokathexis of neutrophils and precursors (retention in BM) Dyserythropoeisis Dysplastic megakaryocytes Increased proportion of blast cells Ringed sideroblasts

Question 548

What are ringed sideroblasts?

Answer 548

Seen in refractory anaemia Prussian blue stain of bone marrow shows blue staind haemosiderin deposits in the mitochondria of erythroid precurors forming an apparent ring around the nucleus

Question 549

Answer 549

Ringed sideroblasts Seen in refractory anaemia Prussian blue stain of bone marrow shows blue staind haemosiderin deposits in the mitochondria of erythroid precurors forming an apparent ring around the nucleus

Question 550

Answer 550

Auer rod AML

Question 551

Answer 551

Myelokathexis Bone marrow smear from a patient with neutropenia due to myelokathexis

Question 552

How can MDS be classified?

Answer 552

Marrow: dysplasia (? hypercellular) RAEB-I RAEB-II Blood: cytopenias/defective cells RA +/- RS (RARS) RCMD RCMD-RS MDS 5q- MDS unclassified

Question 553

Presentation of RA

Answer 553

Presents with anaemia Can be with (RARS) or without ringed sideroblasts

Question 554

What is RCMD?

Answer 554

Refractory cytopenia with multilineage dysplasia Presents with bicytopenia or pancytopenia

Question 555

What is RAEB-I

Answer 555

Refractory anaemia with excess blasts BM blasts 5-10%

Question 556

RAEB-II

Answer 556

BM blasts 11-20%

Question 557

What is the presentation of MDS 5q-

Answer 557

Anaemia with normal platelets

Question 558

What is unclassified MDS

Answer 558

Presents with neutropenia or thrombocytopenia MDS with fibrosis, childhood MDS etc.

Question 559

What is RAEB-T

Answer 559

Refractory anaemia with excess blasts in transofmration Characterised by 21-30% myeloblasts in the marrow Now considered AML

Question 560

How can MDS Px be scored?

Answer 560

International prognostic scoring system in MDS BM blast % Karyotype Cytopenia High risk \>2.5

Question 561

What occurs in myelodysplasia evolution?

Answer 561

Deterioriation of blood counts- indicative of worseing consequence of marrow failure Development of AML (50% in \<1y). AML from MDS has a much poorer prognosis and is not curable 1/3rd die from infection, 1/3rd from bleeding, 1/3rd from leukaemia

Question 562

Treatment of MDS

Answer 562

Supportive: blood products, EPO, G-CSF, Abx Biological modifiers: immunoscupressive therapy: lenalidomide, cytosine analgoue CTx: similar to AML Can also use hydroxyurea Allogenic SCT

Question 563

What is azacytidine?

Answer 563

Cytosine analogue

Question 564

What is lenalidomide?

Answer 564

Thalidomide derivative. Anti-angiogenic, anti-tumour via apoptosis and anti-osetoclastogenic. Used in MDS

Question 565

What causes bone marrow failure

Answer 565

Damage or suppression of stem (all peripheral bloood lines affected) or progenitor cells (bi or unicytopenias

Question 566

How can BM failure be classified

Answer 566

Priamry Secondary

Question 567

What are some primary causes of BM failure?

Answer 567

Congenital: Faconi's anaemia Diamond-Blackfan anaemia Kostmann's syndrome Acquired: idiopathic aplastic anaemia (mutlipotent stem cell)

Question 568

What are the secondary causes of bone marrow failure?

Answer 568

Marrow infiltration Haematological: leukaemias etc. Non-haematological: solid tumours RTx Chemicals: benzenes

Question 569

What drugs can cause bone marrow fialure?

Answer 569

Predicatble: cytotoxic in dose-dependant fashion Idiosyncratic: phyenlybutazone, gold salts (not dose dependant) Abx: chloramphenicol, sulphonamide Carbimazole, thiazides

Question 570

Def: aplastic anaemia

Answer 570

Inability of BM to produce red blood cells HSC numbesr are reduced in BM AA typically refers to just anaemia however these patients can also have a pancytopenia. Symptoms relate to each cytopaenia Patients typicallly present with bleeding problems Can present at any age

Question 571

With what conditions is aplastic anaemia linked?

Answer 571

Leukaemia, PNH

Question 572

How can AA be classified?

Answer 572

Primary Secondary

Question 573

What are the primary causes of AA

Answer 573

Idiopathic (70%): humoral or T cell attack against multipotent HSC Inherited: dyskeratosis congenita, FA, Schwaman diamond syndrome

Question 574

What are the secondary causes of AA?

Answer 574

Due to malignant infiltration Radiation Durgs Viruses CTx SLE

Question 575

Def: severe aplastic anaemia

Answer 575

2/3 of the following peripheral blood features: \<1% reticulocytes (\<20x10^9) Neutrophils (\<0.5) Plt (\<20) BM \<20% cellularity

Question 576

DDx for pancytopenia and hypocellular marrow

Answer 576

Hypoplastic MDS/AML Hypocellular ALL Hairy cell leukaemia Mycobacterial infection (atypical) Anorexia ITP

Question 577

What is NSAA?

Answer 577

Non-severe aplastic anaemia

Question 578

What is the clinical presentaiton of aplastic anaemia?

Answer 578

Classical triad: Anaemia: breathlessness fatigue Leukopenia: infections Plt: easy brusing/bleeding

Question 579

Mx of aplastic anaemia

Answer 579

Supportive: blood products, antibitoics, Fe chelation Marrow recovery drugs: oxymetholone, grwoth factors Immunosuppressive therapy SCT: young patietns iw th adonor

Question 580

Cxs of immunosuppressive therapy in AA?

Answer 580

Relapse of AA Clonal haematological disorders: MDS and leukaemia. PNH

Question 581

What are the inherited BM failure syndromes causing pancytopenias?

Answer 581

Fanconi Anaemia Dyskeratosis congenita Schwachman-Diamond syndrome Familial aplastic anaemia (autosomal and X linked forms) Myelodysplasia Non-haematological syndormes e.g. DS, Dubowitz's

Question 582

What are the inherited BM failure syndromes causing single cytopenias?

Answer 582

Diamond-Blackfan syndrome Kostmann's syndrome Schwchman diamond syndrome Reticular dysgenesis Amegakaryocytic thrombocytopenia with abenst radii

Question 583

What is the inheritance of Fanconi anaemia

Answer 583

AR

Question 584

What are the features of Fanconi anaemia

Answer 584

Presents at 5-10yrs Pancytopenia Skeletal abnormalities: radii, thumbs, renal malformations, microopthalmia, short stature, skin pigmentation MDS (30%), AML risk (10% progress)

Question 585

Answer 585

Fanconi anaemia

Question 586

Cxs of fanconi anaemia

Answer 586

Aplastic anaemia Leukaemia Liver disease Myelodisplasia Cancer (epithelial)

Question 587

What are the features of dyskeratosis congenita

Answer 587

X-linked Chromosome instability (telomere shortening) Skin pigmentation Nail dystrophy Oral leukoplakia BM failure

Question 588

Nail dystrophy Skin pigmentation Oral leukoplakia

Answer 588

Triad seen in Dyskeratosis congenita

Question 589

Answer 589

Dyskeratosis congenita

Question 590

Features of Schwachman-Diamond syndrome

Answer 590

AR Primarily neutropenia Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature AML risk

Question 591

Features of Diamond-Blackfan syndrome

Answer 591

Pure red cell aplasia: normal WCC and plateltes Presents at 1y Dysmorphology

Question 592

Def: myeloproliferative disorders

Answer 592

A group of conditions characterised by clonal proliferation of one or more haematopoeitic component i.e. increased production of mature cells Can be Ph+ve i.e. CML or Ph-ve

Question 593

What are Ph-ve myeloproliferative conditiosn associated with?

Answer 593

JAK2 mutations especially PCV

Question 594

What are the types of myeloproliferative disorders

Answer 594

PCV Essential thrombocythaemia Idiopathic myelofibrosis Idiopathic erythrocytosis CML

Question 595

What is the difference between myeloproliferative, myelodysplasia and leukaemia

Answer 595

MPD: proliferation and full differentiation MDS: ineffective proliferation and differentiation Leukaemia: proliferation without differentiation

Question 596

Polycythaemia

Answer 596

Riaed red cell mass Hb Red Cell count PCV

Question 597

Causes of polycythaemia

Answer 597

Primary: PCV Familial polycythaemia Secondary: Raised EPO (disease sates, renal Ca, high altitude, chronic hypoxia)

Question 598

What is pseudo polycthaemia?

Answer 598

Red cell mass normal but reduced plasma volume e.g. dehydration, burns, vomiting, diarrhoea, cigarette smoking

Question 599

Features of PCV

Answer 599

Predominant presentation of increasd RBCs Production independent of normal erthropoeisis Often a true increase in plasma volume Increases with age Point mutations of JAK2 (V617F)

Question 600

Point mutations of JAK2 (V617F)

Answer 600

PCV

Question 601

Cxs of PCV

Answer 601

Thrombosis occurs if platelets not reduced Leukaemia may occur Myelofibrosis may occur

Question 602

Clinical features of PCV

Answer 602

Incidental Dx on routine testing Hyperviscosity/hypervolaemia/hypermetabolism: blurred vision, headaches, light-headedness, stroke, fatigue, dyspnoea Plethroic: red nose, gout, thrombosis, retinal vein enorgement, erythromelagia Splenomegaly Increaseed histamein release: aquagenic pruritus (contact with water0 and peptic ulcers

Question 603

Ix in PCV

Answer 603

Raised Hb Hct May be increased platelets WCC can be normal or increased No blast cells Increased red cell mass and plasma volume BM: increased ceullarity mainly affecting erythroid cells. Low serum EPO JAK2 V617F mutation is dxic.

Question 604

How can blood volume be measured?

Answer 604

Isotope dilution method

Question 605

Diagnostic criteria for PCV

Answer 605

Raised RC mass \>25% Hb \>18.5g/l in men, 16.5 in women Absence of other causes of erythrocytosis BM cellularity

Question 606

Treatment of PCV

Answer 606

Veensection Hydroxycarbamide: cytoreductive therapy Aspirin: keep platelets below 400

Question 607

Features of idiopathic erythrocytosis

Answer 607

Absence of JAK2 V617F mutation Isolated erythrocytosis, low EPO Less likely to turn to myelofibrosis or AML. Treat with venesection only

Question 608

Features of esssential thrombocythaemia

Answer 608

Chronic MPD involving megakaryocytic lineage Sustained plt \>600 Incidence is at 55 and 30y F\>M at 55, equal at 30

Question 609

Clinical presentation of essential thrombocythaemia

Answer 609

Incidental Thrombosis: arterial or venous, CBA, gangrene etc. Bleeding: mucous membranes and cutaenous Headaches, dizziness and visual disturbances Modest splenomegaly

Question 610

Dx of essential thrombocythamia

Answer 610

Plt \>600 Megakaryocyte abnormalities or clustering on blood film No evidence of reactive thrombocytosis No preceding or coincidental myeloproliferative disorder or dysplasia Megakaryocytes in BM

Question 611

Mx of essential thrombocythaemia

Answer 611

Aspirin: thrombosis prevention Anagrelide: reduces fromation of plts from megakaryocytes Hydroxycarbamide: supress other cells Alpha IFN in patients \<40

Question 612

Px of essential thrombocythaemia

Answer 612

Normal lifespan may not be changed Leuakaemic transofrmation in 5% Myelofibrosis also uncommon

Question 613

Def: myelofibrosis

Answer 613

A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells associated with reactive bone marrow fibrosis and extramedullary haematopoiesis

Question 614

How can myelofibrosis be classified?

Answer 614

Primary: idiopathic Secondary: following PRV, ET, leukaemia etc.

Question 615

Clinical presentation of idiopathic myelofibrosis

Answer 615

Elderly Pancytopenia related symptoms Extramedullary haematopoeisis- hepatomegaly, massive splenomegaly, WL, fever Can present with budd-chiari syndrome Hypermetabolic state: weigtht loss, fatigue, dyspnoea, night sweats, hyperuricaemia.

Question 616

BM dry tap

Answer 616

Myelofirbrosis

Question 617

Tear drop poikilocytes, (dacrocyte) leukoerythroblasts

Answer 617

Myelofibrolsis

Question 618

What are the stages of myelofirgbosis?

Answer 618

Prefibrotic stages: mild blood changes, hypercellular marrow. Fibrotic stage: Liver and spleen: splenogmealy and extramedullary haemopoiesis Blood changes: leucoerythroblastic picture, tear drop poikilocytes, giant platelets, circulating megakaryocytes BM: dry tap, prominent collagen fibrosis and reticulin. New bone formation and osteosclerosis later

Question 619

Treatment of myelofibrosis

Answer 619

Anaemia: transfusion (become difficult because of splenomegaly- splenectomy) Plt Cytoreductive therapy: hydroxycarbamide Thaildomide with or without prednisolone BM transplant (experimental)

Question 620

What are the bad prognostic signs in myelofibrosis?

Answer 620

Severe anaemia Thrombocytopenia Massive splenomegaly

Question 621

What is the relationship between EPO/TPO and JAK2

Answer 621

Normally stimulate the receptor that is associated with JAK2.

Question 622

Prevalence of JAK2 mutations in myeloproliferative disorders

Answer 622

PCV 99% ET 50% IM 50%

Question 623

What is the MTD for bone marrow?

Answer 623

Maximum tolerated dose of radiation 1gy12gy

Question 624

When are there cerebrovascular events following radiation?

Answer 624

\>30gy

Question 625

What are the methods for SCT?

Answer 625

Autologous Allogenic

Question 626

Features of autologous BM transplant

Answer 626

Give patient growth factors, collect SC and freeze them. Thaw and reinfuse after high dose CTx Indicated in acute leukaemia, lymhpoma, solid tumours, myeloma, CLL

Question 627

Features of allogenic SCT

Answer 627

Patient is given high dose RTx and CTx and bone marrow or peripheral blood stem cells are transfused from a matched donor Indicated in acute leukaemia, chronic leukaemia, myeloma, BM failure, congenital immune deficiencies, lymphoma

Question 628

What are the complications of SCT?

Answer 628

Graft failure Infections GvHD Relapse

Question 629

Mx of GvHD

Answer 629

Corticosteroids Cyclosporine Tacroliums Mycophenylate mofetil Monoclonal Abs Photophersis Total lymphoid irradiation

Question 630

What are the different phases following allogenic BMT

Answer 630

Aplastic phase (0-3w): Gram positive and negative bacteria, candida, sV, RSV GvHD phase (3w-3/6m): CMV, VZV, HHV, aspergillus, candida, adenovirus Late phase (6m-yeasr): pneuomoccoal, H influenza, VZV CMV is the prime suspect in transplant patients.

Question 631

When can the first mutation for ALL occur? What can happen

Answer 631

Can occur in utero Pre-leukaemic cells carrying this mutation can spread from one twin to another

Question 632

What is TAM

Answer 632

Transient abnromal myelopoiesis is a specific type of neonatal leukaemia. Myeloid leukaemia with major involvement of the megakaryocyic lineage Remits spontaneously but relapse can occur 1-2 years later in 1/4

Question 633

WCC Neutrophil Lymphocyte Hb MCV In neonate

Answer 633

26.1 15 10 220 120

Question 634

WCC Neutrophil Lymphocyte Hb MCV In 2 year old

Answer 634

10.1 2 7 110 75

Question 635

WCC Neutrophil Lymphocyte Hb MCV In adult

Answer 635

4-11 2-7.5 1. 3-4 11. 5-16.5 and 13-18 77-95

Question 636

Hb in children

Answer 636

No gender difference

Question 637

Why may vit deficiencies manifest in childhood?

Answer 637

Due to rapid growth Fe deficiency common during growth spurt FOlica acid deficiency can also occur

Question 638

What can cause polycythaemia in nneonates?

Answer 638

TTTS Intrauterine hypoxia Placental insufficiency

Question 639

What can cause anaemia in neonate?

Answer 639

TTTS Foetal to maternal transfusion Parvovirus infection Haemorrhage from the cord of placenta

Question 640

Structure of HbA

Answer 640

a2b2: present in late foetus, infant, child and adult

Question 641

HbA2

Answer 641

A2D2, present in the infant, child and adult

Question 642

HbF

Answer 642

A2G2, present in foetus and infant

Question 643

Normal Hb beta chain gene cluster Sickle cell trait Sickle cell disease Sickle cell c Sickle cell/beta thal

Answer 643

beta beta beta betas betas betas betas betac betas betathal

Question 644

Why does Sickle cell disease differ between children and adult?

Answer 644

Different distribution of red bone marrow: susceptible to infarction *dactylitis, acute chest syndrome, painful crisis, stroke* Infant has funcitoning spleen *splenic sequestration: severe anaemia, schock and death.* Imamture immune system means they are more susceptible to pneumococcus and parvovirus *First exposure to parvovrius will lead to RCA* Infant has higher requirements for folic acid *hyperplastic erythropoeisis requires folic acid*

Question 645

What is splenic sequestration

Answer 645

Acute pooling of a large percentage of circulating red cells in the spleen Leads to acute splenic enlargement and reduciton in Hb

Question 646

Clinical effects of poorly treated thalassaemia major

Answer 646

Anaemia: heart failure and growth retardation Erythropoietic driveL bone expansion, hepatomegaly, splenomegaly. Fe overload: heart and gonadal failure

Question 647

What are the types of inherited defects of coagulation?

Answer 647

Haemophilia A B Von Willebrand disease

Question 648

What factor is affected in haemophilia A?

Answer 648

Factor VIII

Question 649

What factor is affected in haemophilia B?

Answer 649

Factor IX

Question 650

Presentation of haemophilia

Answer 650

Bleeding after circumcision Haemarthrosis when starting to walk Bruises and post-traumatic bleeding

Question 651

Dx of haemophilia

Answer 651

Umbilical cord bleeding Heel prick Haematoma formation after injections FHx Coagulation screen Plt count Assay of specific coagulation factors

Question 652

Mx of haemophilia

Answer 652

Dx Counselling Treatment of bleeding epsidoes Use of prophylactic coagulation factors

Question 653

Presentation of Von Willebrand

Answer 653

Mucosal bleeding, brusies and post-traumatic bleeding

Question 654

Presentaiton of autoimmune thrombocytopenic purpurae?

Answer 654

Petechiae, bruises, blood blisters in mouth Ddx: henoch schonlein, NAI, coagulation factor defected

Question 655

Mx of AITP?

Answer 655

Observation Corticosteroids High dose IVIG IV anti-RhD if Rh-positive

Question 656

When is AML more common than ALL in children

Answer 656

In those \<1y/o

Question 657

Causes of gangrene

Answer 657

Vascular: peripheral vascular disease Blood: PCV, cold agglutinin, essential thrombocythaemia

Question 658

What blood abnormalities are associated with RA?

Answer 658

Anaemia of chronic disease Fe deficiency due to aspirin or NSAID use Neutropenia or thrombocytopenia from NSAID use Felty's syndrome Increased ESR

Question 659

Felty's syndrome

Answer 659

RA Splenomegaly Neutropenia

Question 660

Child with swollen single joint

Answer 660

Haemophilia NAI Osteomyelitis Septic arthritis

Question 661

Mx of TTP

Answer 661

PLEX

Question 662

Draw the process of haemostasis

Answer 662

Question 663

What are the constituents of the priamry platelet plug

Answer 663

Platelets VW factor Vascular endothelium

Question 664

What are the functions of the endothelium?

Answer 664

Synthesis PGI2 VwF Plasminogen activators Thrbomomdoulin Acts as the main barrier between the blood and the procoagulant subendothelium

Question 665

What is VW factor?

Answer 665

Glycoprotein made in endothelium and platelts. Monomers link to form a large multimeric protein Each vWF monomer has a binding domain for platelets, collagen and factor VIII

Question 666

What is the lifespan of a platelt?

Answer 666

10d 1/3rd stored in the spleen

Question 667

Draw the coagulation cascade

Answer 667

Question 668

Draw the process of platelet adhesion and aggregation

Answer 668

Question 669

Draw the process of arachidonic acid metabolism

Answer 669

Question 670

What factors are involved in fibrinolysis

Answer 670

Anthithrombin binds to FXa to form antibthrombin complex Activity/binding is increased by heparin Protein C/ Protein S Plasmin: plasminogen activated via tPA, this breaks down fibrin clot to produce fibrin degradation productions

Question 671

What acquired defects lead to haemorrhagic disorder?

Answer 671

Liver disease Vit K deficiency AI disease e.g. platelet destruction, trauma, DIC, scurvy

Question 672

What inherited factors lead to haemorrhagic disorders?

Answer 672

Platelet abnormalities Blood vessel wall abnormalities Clotting factor deficiencies Excess fibrinolysis

Question 673

What differentiates between disorders of platelets and disorders of coagulation factors?

Answer 673

Site of bleeding: skin, mucuous membranes. Coagulation factor is in soft tissues, joints, mmuscles. Petechiae seen in platelet disorders Small superficial echymoses, large deep in coagulation haemarthroses common in coagulation factor Bleeding after cuts and scratches seen in platelet disorders Often severe delayed bleeding after surgery in coagulation

Question 674

What causes the differnece in the characteristics of platelt and coagulation factor disorders

Answer 674

Platelets are involved in priamry haemostasis Coagulation factors are involved in the formation of fibrin clot

Question 675

How can platelet disorders be classified?

Answer 675

Decreased number Defective funciton ITP

Question 676

What are somecauses of decreased platelet number?

Answer 676

Decreased produciton Decreased survival Increased utilisation Abnormal distribution

Question 677

What are some causes of defective platelet function?

Answer 677

Aspirin Thrombasthenia

Question 678

What are the feautres of Glanzmann's thrombasthenia

Answer 678

Rare congenital coagulopathy where platelets lack GIPIIb/IIIa This means that fibrin crosslinking can occur

Question 679

Acquired causes of coagulation factor disorders?

Answer 679

DIC, liver diease, Vit K deficiency, warfarin overdose

Question 680

APTT in haemophilia

Answer 680

Prolonged

Question 681

Lab features of DIC

Answer 681

Prolonged APTT PT TT

Question 682

Mx of clotting disorders in liver disease

Answer 682

For prolonged PT/PTT: Vit K For low fibrinogen: cryoprecipitate, fibrinogen concentrate For DIC: (elevated d-dimer), replacement therapy

Question 683

Acanthocytse (spur/spike cells)

Answer 683

RBCs showing many spicules Seen in abetalipoproteinaemia, liver disease, hyposplenism

Question 684

Basophilic RBC stippling

Answer 684

Accelerated erythropoeisis or defective Hb synthesis. Small dots seen at the periphery (rRNA) Lead poisoning, megaloblastic anemia, myelodysplasia, liver disease, Hbopathy e.g. thalassaemia

Question 685

Burr cells (ecinthocyte)

Answer 685

Irregulalry shaped cells Uricaemia, GI bleeding, stomach carcinoma

Question 686

Heinz Bodies

Answer 686

Inclusions within RBCs of denatured Hb G6PD Chronic liver disease

Question 687

Howell-Jolly bodies

Answer 687

Basophilic nuclear remnants in RBCs Post-splenectomy or hyposplenism (e.g. SCD, coeliac, congenital, UC/Crohns, myeloproliferative disease, amyloid) Megaloblastic anaemia Hereditary spherocytosis

Question 688

Leucoerythroblastic anaemia

Answer 688

Marrow infiltration: nucleated RBCs and primitive WBCs in peripheral blood Marrow infiltration i.e. myelofibrosis, malignancy

Question 689

Polychromasia

Answer 689

Sign of reticulocytes. Red blood cells of multiple colours due to differing amounts of Hb in RBC Premature/inappropriate release from BM

Question 690

Reticulocytes

Answer 690

Immature RBCs show mesh like network of ribosomal RNA which becomes visislbe with certain stains i.e. methylene blue. Increased in HA decreased in AA

Question 691

Right shift

Answer 691

Hypermature white cells (hypersegmented polymorphs \>5 lobes to nucleus) Megaolblastic anaemia, uraemia, liver disease

Question 692

Rouleaux formation

Answer 692

Red cells stacked on one another Chronic inflammation Paraproteinemia MM

Question 693

Stoamtocytes

Answer 693

Central pallor is straight or curved rod-like shape. RBCs appear as smiling faces or fish mouth Hereditary stomatocytosis, high ETOH, liver disease

Question 694

Target cells (codocyte)

Answer 694

Bull's eye appearance in central pallor Liver disease, hyposplenism, thalassaemia, IDA

Question 695

Def: anaemia

Answer 695

Men \<13.5 Women \<11.5

Question 696

Causes of anaemia

Answer 696

Reduced production Increased loss Increased plasma volume

Question 697

Symptoms and signs of anaemia

Answer 697

Fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia Pallor Hyperdynamic circulation e.g. tachycardia, flow murmurs leading to hert failure (severe anaemia- \<8)

Question 698

Causes of microcytic anaemia FAST

Answer 698

Fe deficiency Anaemia of chronic disease Sideroblastic anemia Thalassaemia (in the absence of anaemia)

Question 699

Causes of normocytic anaemia

Answer 699

Acute blood loss Anaemia of chronic disease BM failure Renal failure Hypothyroidsim Haemolysis Pregnancy

Question 700

Causes of macrocytic anaemia FATRBC

Answer 700

Fetus (pregnancy) Antifolates (phenytoin) Thyroid (hypo) Reticulocytosis B12 or folate deficiency Cirrhosis (ETOH excess of liver disease) Myelodysplastic syndromes

Question 701

Signs of IDA

Answer 701

Koilonychia Atrophic glossitis Angular cheilosis Post cricoid webs (Plummer vinson syndrome) Brittle hair and nails

Question 702

Blood film in IDA

Answer 702

Microcytic Hypochormic Anisocytosis (varying size) Poikilocytosis (varying shape) Pencil cells

Question 703

IDA=

Answer 703

Blood loss until proven otherwise

Question 704

Causes of IDA

Answer 704

Blood loss Increased utilisation Decreased intake Decreased absoprtion Intravascular haemolysis

Question 705

Blood loss in IDA

Answer 705

GI loss Meckel's diverticulum Peptic ulcers, gastritis Polyps/CRC (most common cause in adults \>50) Menorrhagia Hookworm infestation

Question 706

Increased utilisation IDA

Answer 706

Pregnancy Lactation Growth in children

Question 707

Decreased intake IDA

Answer 707

Prematurity Infants/children/elderly Loss of Fe each day fetus is not in utero. Suboptimal diet

Question 708

Decreased absorption IDA

Answer 708

Coeliac Post-gastric Sx Absence in villous surphace of duodenum Rapid transit: reduced acid which normally helps Fe absoprtion

Question 709

Intravascular haemolysis IDA

Answer 709

MAHA PHA Chornic loss of Hb in urine

Question 710

Treatment of IDA

Answer 710

Treat cause Oral Fe

Question 711

Side effects of oral Fe

Answer 711

Nausea Abdo discomfort Diarrhoea Constipation Black stools

Question 712

Pathophysiology of anaemia of chornic disease

Answer 712

Inflammatory cytokines (IFNs, TNF, IL1) reduce EPOR production and thus EPO synthesis in kidneys Fe metabolism is dysregulated: IL6 and LPS stimulate liver to make hepcidin which decreases Fe absortion from the gut through transferrin inhbition and causes Fe accumulation in macrophages

Question 713

Causes of ACD

Answer 713

Chronic infection Vasculitis RA Malignancy

Question 714

Anaemia of chronic disease in renal failure

Answer 714

Not cytokine deficiency but due to EPO deficiency

Question 715

Ferritin in ACD

Answer 715

High due to sequestered Fe in macrophages unless the patient has coexisting IDA

Question 716

Sideroblastic anaemia causes

Answer 716

Ineffective erythropoeisis: Fe loading causes haemosiderosis

Question 717

Causes of sideroblastic anaemia?

Answer 717

Myelodysplastic disorders Following CTx Irradiation ETOH excess Pb excess Anti-TB drugs Myeloproliferative disease

Question 718

Rx of sideroblastic anaemia

Answer 718

Remove cause Vitamine B6

Question 719

NB with ferritin

Answer 719

Acute phase marker Check CRP with every raised ferritin seen in clinical practice

Question 720

Causes of macrocytosis

Answer 720

Megaloblastic Non-megaloblastic Other haematological disease

Question 721

Causes of megaloblastic macrocytosis

Answer 721

B12 deficiency Folate deficiency Cytotoxic drugs

Question 722

Causes of non-megaloblastic macrocytosis

Answer 722

ETOH (most common cause of macrocytosis without anaemia) Reticulocytosis Liver disease Hypothyroidsim Pregnancy

Question 723

Other haematological disease leading to macrocytosis

Answer 723

Myelodysplasia Myeloma Myeloproliferative disorders Aplastic anaemia

Question 724

Megaloblastic blood film=

Answer 724

Hypersegmented polymorphs Leucopenia Macrocytosis Anaemia Thrombcoytopenia

Question 725

Sources of Vit B1

Answer 725

Meat and dairy products (large body stores)

Question 726

Causes of B12 deficiency?

Answer 726

Dietary Malabsorption (stomach- pernicious anaemia, terminal ileum- resection in Crohn's, bacterial overgrowth, tropical sprue, tapeworms

Question 727

Clinical features of B12 deficiency?

Answer 727

Mouth: glossitis, angular cheilosis Neuropsychiatric: irritability, depression, psychosis, dementia Neurological: paraesthesia, peripheral neuropathy (loss of vibration anjd proprioception first, absent ankle reflex, spastic parpereisis, SACD of SC)

Question 728

Tests for Pernicious anaemia

Answer 728

Parietal cell Abs IF Abs

Question 729

Treatment of B12 deficiency

Answer 729

IM hydroxycobalamin

Question 730

Dietary sources of folate

Answer 730

Green vegetables Nuts Yeast Liver Low body stores cannot produce de novo

Question 731

Causes of folate deficiency

Answer 731

Poor diet Increased demand Malabsorption Drugs: ETOH, anti-epileptics, methotrexate, trimethoprim

Question 732

Treatment of folic acid deficiency

Answer 732

Give oral folic acid If cause of anaemia is not known then folic acid must not be given as it will exacerbate the neuropathy of B12 deficiency

Question 733

What to remember in coagulation pathway INTRINSIC

Answer 733

Next factor starts iwth letter of previous factor

Question 734

What test examines the intrinsic pathway What can it monitor?

Answer 734

APTT Heparin therapy

Question 735

What test monitors the extrinsic pathway? What can it be used to monitor?

Answer 735

PT Warfarin therapy

Question 736

What test can be used to examine the common pathway?

Answer 736

TT

Question 737

What are some congenital and acquired vascular defects

Answer 737

Congenital: Osler-Weber-Rendu syndrome, Ehlyer's danlos Senile purpura Infection Steroids Scurvy

Question 738

Osler Weber Rendu

Answer 738

Osler-Weber-Rendu disease (OWRD) is a rare autosomal dominant disorder that affects blood vessels throughout the body (causing vascular dysplasia) and results in a tendency for bleeding. (The condition is also known as hereditary hemorrhagic telangiectasia [HHT]; the two terms are used interchangeably in this article.) The prognosis varies, depending on the severity of symptoms; generally, it is good, as long as bleeding is promptly recognized and adequately controlled. HHT is manifested by mucocutaneous telangiectases and arteriovenous malformations (AVMs), a potential source of serious morbidity and mortality.[1]Lesions can affect the nasopharynx, central nervous system (CNS), lung, liver, and spleen, as well as the urinary tract, gastrointestinal (GI) tract, conjunctiva, trunk, arms, and fingers.

Question 739

Mx of Chronic ITP

Answer 739

Seen in adults Doesn't resolve spontaenously Requires IVIG, steroids, splenectomy

Question 740

Dx of Haemophilia A

Answer 740

Raised APTT, Normal PT, reduced factor VIII assay

Question 741

Mx of Haemophilia A

Answer 741

Avoid NSAIDs and IM injections Desmopressin Factor VIII concentrates which is life long

Question 742

What is Christmas Disease?

Answer 742

Haemophilia B Factor 9 deficiency

Question 743

Dx of vWD

Answer 743

Increased APPT Increaesd bleeding time Reduced Factor VIII (vWF is a carrier) Reduced vWF concentrates

Question 744

Buses that go down high street ken 27, 9 and 10

Answer 744

Clotting factors requiring vitamin K for synthesis

Question 745

INR APTT TT Plt Bleeding time In heparin

Answer 745

Raised Raised ++ Raised ++ N N

Question 746

INR APTT TT Plt Bleeding time in DIC

Answer 746

Raised ++ Raised ++ Raised ++ Redcued Increased with raised d-dimer

Question 747

INR APTT TT Plt Bleeding time in liver disease

Answer 747

Raised Raised N/raised N/decreased N/ raised Transaminases elevated

Question 748

INR APTT TT Plt Bleeding time In platelet defect

Answer 748

N N N N Raised

Question 749

INR APTT TT Plt Bleeding time in Vit K deficiency

Answer 749

Raised ++ Raised N N N

Question 750

INR APTT TT Plt Bleeding time In haemophilia

Answer 750

N Raised ++ N N N

Question 751

INR APTT TT Plt Bleeding time in vWF

Answer 751

N Raised ++ N N Raised

Question 752

The main component involved in stabilising the primary haemostatic plug. ## Footnote A. Fibrinogen B. Megakaryocyte C. Fibrin D. Erythrocyte E. Tissue plasminogen-activator (t-PA) F. Protein C G. Antithrombin III H. Plasmin I. Thromboxane A2 J. a2 macroglobulin K. Cycloxygenase L. Platelet M. Endothelial cell

Answer 752

Fibrin

Question 753

A serine protease which assists in the break down of blood clots by binding to the clot and localising agents which break it down.

Answer 753

TpA

Question 754

A potent inhibitor of plasmin in the blood.

Answer 754

a2 microglobulin

Question 755

A 25 year old man presents to the Emergency Department a day after attending his dentist for a routine check-up. After treatment at the dentists the previous day, his gums had not stopped bleeding. On investigation, his APTT and bleeding time are prolonged but a normal PT. ## Footnote A. Autoimmune thrombocytopenic purpura B. Factor VIII deficiency C. Christmas disease D. Megakaryocyte E. Factor XII deficiency F. Thromboxane A2 G. von Willebrand deficiency H. Sensitised platelet I. Haemophilia J. Marfan syndrome K. Vitamin K deficiency L. Ehlers-Danlos syndrome M. Prostacyclin PGI2

Answer 755

vWD

Question 756

A 16 year old girl presents to the Haematology Outpatients clinic describing a fluctuating history of easy bruising, epistaxis and menorrhagia. On investigation there is a thrombocytopaenia with increased megakaryocytes on BM examination ## Footnote A. Autoimmune thrombocytopenic purpura B. Factor VIII deficiency C. Christmas disease D. Megakaryocyte E. Factor XII deficiency F. Thromboxane A2 G. von Willebrand deficiency H. Sensitised platelet I. Haemophilia J. Marfan syndrome K. Vitamin K deficiency L. Ehlers-Danlos syndrome M. Prostacyclin PGI2 Response Feedback: F

Answer 756

AITP

Question 757

Which protein, important in haemostasis, is vitamin K dependent but is not a serine protease?

Answer 757

Protein S

Question 758

Which key clotting factor activates both factors V and VIII, and also activates protein C?

Answer 758

Thrombin

Question 759

Which option is required as a cofactor for protein C activity?

Answer 759

Protein S

Question 760

A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods. ## Footnote A. Sickle cell anaemia B. Factor V Leiden C. Christmas Disease D. Warfarin overdose E. Henoch – Schönlein Purpura F. Bile acid malabsorption G. Antiphospholipid antibody syndrome H. Malignancy I. Disseminated intravascular coagulation J. Vitamin K Deficiency K. Osler-Weber-Rendu Syndrome L. Haemophilia A M. Von Willebrand’s Disease N. B-Thalassaemia

Answer 760

Osler Wever Rendu 1) A rare autosomal dominant disorder. Alternative name = hereditary haemorrhagic telangiectasia. There is a structural abnormality of the blood vessels, resulting in telangiectases, which are thin walled so are likely to bleed. This leads to haemorrhage and anaemia. It is more common in females, and may not present until later in life. Epistaxis is the commonest presenting symptom. This patient is feeling tired, not just because of her 4 children, but because she also has iron deficiency anaemia.

Question 761

22 year old Saharawi refugee presents with anaemia, weight loss, loose stools and blood tests reveal an increased PT and slightly increased APTT, with normal thrombin time and platelet count. ## Footnote A. Sickle cell anaemia B. Factor V Leiden C. Christmas Disease D. Warfarin overdose E. Henoch – Schönlein Purpura F. Bile acid malabsorption G. Antiphospholipid antibody syndrome H. Malignancy I. Disseminated intravascular coagulation J. Vitamin K Deficiency K. Osler-Weber-Rendu Syndrome L. Haemophilia A M. Von Willebrand’s Disease N. B-Thalassaemia

Answer 761

Vit K deficiency revalence of coeliac disease is highest in Saharawi refugees. This patient has coeliac disease, and as a result of malabsorption is losing weight and has loose stools (steatorrhoea), and vitamin K deficiency. The blood results related to vitamin K deficiency.

Question 762

A 5 year old boy has the following blood results: normal PT, increased APTT, normal platelet count, decreased VIII:C and decreased vWF. ## Footnote A. Sickle cell anaemia B. Factor V Leiden C. Christmas Disease D. Warfarin overdose E. Henoch – Schönlein Purpura F. Bile acid malabsorption G. Antiphospholipid antibody syndrome H. Malignancy I. Disseminated intravascular coagulation J. Vitamin K Deficiency K. Osler-Weber-Rendu Syndrome L. Haemophilia A M. Von Willebrand’s Disease N. B-Thalassaemia

Answer 762

The most common hereditary bleeding disorder, affect 1% of the population. vWF is a carrier protein for factor VIII and stabilises it. Mutation is in chromosome 12.

Question 763

Dangerous combination with no added efficacy and increased GI bleed. A. Dalteparin (LMWH) B. Aspirin C. 10mg, 10mg, 5mg, measure on 4th day then every 2 days D. APTT E. Calciparone F. Pentapolysaccharide G. Clopidogrel H. Warfarin I. Prothrombin time (PT) J. Clopidogrel and aspirin K. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days L. Thrombin time (TT) M. LMWH and aspirin N. Dipyridamole modified release (MR) and aspirin O. Unfractionated heparin (UFH) P. Streptokinase

Answer 763

Clopidogrel and aspirin

Question 764

Old model of starting warfarin ## Footnote A. Dalteparin (LMWH) B. Aspirin C. 10mg, 10mg, 5mg, measure on 4th day then every 2 days D. APTT E. Calciparone F. Pentapolysaccharide G. Clopidogrel H. Warfarin I. Prothrombin time (PT) J. Clopidogrel and aspirin K. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days L. Thrombin time (TT) M. LMWH and aspirin N. Dipyridamole modified release (MR) and aspirin O. Unfractionated heparin (UFH) P. Streptokinase

Answer 764

10mg, 10mg, 5mg, measure on 4th day then every 2 days

Question 765

Tait model of starting warfarin

Answer 765

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

Question 766

Side effects include cutaneous necrosis ## Footnote A. Dalteparin (LMWH) B. Aspirin C. 10mg, 10mg, 5mg, measure on 4th day then every 2 days D. APTT E. Calciparone F. Pentapolysaccharide G. Clopidogrel H. Warfarin I. Prothrombin time (PT) J. Clopidogrel and aspirin K. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days L. Thrombin time (TT) M. LMWH and aspirin N. Dipyridamole modified release (MR) and aspirin O. Unfractionated heparin (UFH) P. Streptokinase

Answer 766

Warfarin

Question 767

The drug most likely to cause thrombocytopaenia with paradoxical thrombosis A. Dalteparin (LMWH) B. Aspirin C. 10mg, 10mg, 5mg, measure on 4th day then every 2 days D. APTT E. Calciparone F. Pentapolysaccharide G. Clopidogrel H. Warfarin I. Prothrombin time (PT) J. Clopidogrel and aspirin K. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days L. Thrombin time (TT) M. LMWH and aspirin N. Dipyridamole modified release (MR) and aspirin O. Unfractionated heparin (UFH) P. Streptokinase

Answer 767

UFH

Question 768

Indicated as thrombotic prophylaxis in DIC ## Footnote A. Dalteparin (LMWH) B. Aspirin C. 10mg, 10mg, 5mg, measure on 4th day then every 2 days D. APTT E. Calciparone F. Pentapolysaccharide G. Clopidogrel H. Warfarin I. Prothrombin time (PT) J. Clopidogrel and aspirin K. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days L. Thrombin time (TT) M. LMWH and aspirin N. Dipyridamole modified release (MR) and aspirin O. Unfractionated heparin (UFH) P. Streptokinase

Answer 768

Dalteparin (LMWH)

Question 769

A 65 year old patient presents with hepatosplenomegaly. He is mildly anaemic and thrombocytompenic. A blood monocyte count of 1.2 x 109/l is observed. Bone marrow aspirate reveals ring sideroblasts at 15% of total blasts. Auer rods are observed. ## Footnote A. Refractory Anaemia with Ring Sideroblasts B. Acute Myeloid Leukaemia C. Chronic Myelomonocytic Anaemia D. Refractory Anaemia with excess of Blasts II E. Myelodysplastic syndrome,unclassifiable F. Refractory Cytopaenia with Multilineage Dysplasia G. Refractory anaemia H. Aplastic Anaemia I. Secondary Sideroblastic Anaemia J. Refractory Anaemia with excess of Blasts I K. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

Answer 769

CML

Question 770

A 58 year old lady complains of lethargy and “easy bruising”. She presents with purpura. Her FBC reveals Hb 10.5g/dl; WBCs 2.3x109/l and platelets 8x109/l. Blood film reveals \<1% Blasts, and marrow aspirate shows 20% dysplasia in erythroid lineage, 60% dysplasia in platelet lineage, 5% dysplasia in granulocyte lineage, and less than 5% blasts. ## Footnote A. Refractory Anaemia with Ring Sideroblasts B. Acute Myeloid Leukaemia C. Chronic Myelomonocytic Anaemia D. Refractory Anaemia with excess of Blasts II E. Myelodysplastic syndrome,unclassifiable F. Refractory Cytopaenia with Multilineage Dysplasia G. Refractory anaemia H. Aplastic Anaemia I. Secondary Sideroblastic Anaemia J. Refractory Anaemia with excess of Blasts I K. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

Answer 770

Re Q3, to count as significant, dysplasia must involve at least 10% of cells in a lineage. To count as RCMD, at least 2 MYELOID lineages must be dysplastic, and there must be bi or pancytopenia in the peripheral blood. (This can include anaemia!)

Question 771

A 78 year old male patient with recurring infections of the face and maxillary sinuses associated with neutropenia. His bloods are: Hb 9.8 g/dl; WBC 1.3x109/l; Neutrophils 0.3x109/l; platelets 38x109/l.The lab informs you that there are Blasts approximately compromise 17% of bone marrow aspirate ## Footnote A. Refractory Anaemia with Ring Sideroblasts B. Acute Myeloid Leukaemia C. Chronic Myelomonocytic Anaemia D. Refractory Anaemia with excess of Blasts II E. Myelodysplastic syndrome,unclassifiable F. Refractory Cytopaenia with Multilineage Dysplasia G. Refractory anaemia H. Aplastic Anaemia I. Secondary Sideroblastic Anaemia J. Refractory Anaemia with excess of Blasts I K. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

Answer 771

Refractory Anaemia with excess of Blasts II

Question 772

A 74 year old woman with high-normal platelet count. Bone marrow aspirate shows hyperplasia of hypolobulated micromegakaryocytes. Responds well to lenalidomide. ## Footnote A. Secondary aplastic anaemia B. 5q syndrome C. Idiopathic aplastic anaemia D. Acute myeloid leukaemia E. Inherited aplastic anaemia F. Myelofibrosis G. Refractory cytopenia with multilineage dysplasia H. Juvenile myelomonocytic leukaemia I. Refractory anaemia with an excess of blasts J. Refractory anaemia

Answer 772

5q syndrome

Question 773

In this case haemoglobin is normal but there is a reduction in platelets and neutrophils ## Footnote A. Secondary aplastic anaemia B. 5q syndrome C. Idiopathic aplastic anaemia D. Acute myeloid leukaemia E. Inherited aplastic anaemia F. Myelofibrosis G. Refractory cytopenia with multilineage dysplasia H. Juvenile myelomonocytic leukaemia I. Refractory anaemia with an excess of blasts J. Refractory anaemia

Answer 773

Refractory cytopenia with multilineage dysplasia

Question 774

A consultant grills you on a ward round: there is a patient with a WBC of 140 x109/L, Hb 12 g/dL, Platelet count 320 x109/L. She complains of tiredness, night sweats, fever and abdominal pain. Her spleen is markedly enlarged. Blood film shows blasts, neutrophils, basophils. How would you treat her? A. Pseudopolycythaemia B. Splenomegaly C. Haematocrit D. Hydroxycarbamide E. Idiopathic myelofibrosis F. Erythropoeitin G. Venesection H. Chlorambucil I. Acute myeloid leukaemia J. Chronic myeloid leukaemia K. Polycythaemia vera L. Imitanib M. Essential thrombocythaemia N. Melphalan O. Tear drop poikilocytes P. Microcytosis

Answer 774

Imatinib

Question 775

You are asked to see a 76 year old man on the wards, who presented with fatigue, dyspnoea, bleeding gums and nightsweats. His abdomen is massively enlarged. You read his notes and find ‘bone marrow aspirate: ‘dry tap’. What would you expect to see on the blood film? A. Pseudopolycythaemia B. Splenomegaly C. Haematocrit D. Hydroxycarbamide E. Idiopathic myelofibrosis F. Erythropoeitin G. Venesection H. Chlorambucil I. Acute myeloid leukaemia J. Chronic myeloid leukaemia K. Polycythaemia vera L. Imitanib M. Essential thrombocythaemia N. Melphalan O. Tear drop poikilocytes P. Microcytosis

Answer 775

Tear drop poikilocytes

Question 776

A 55 year old female has a past medical history of deep vein thrombosis. She also complains of easy bruising. Her platelet count is 770 x109/L, CRP is 4mg/L. You prescribe aspirin. ## Footnote A. Pseudopolycythaemia B. Splenomegaly C. Haematocrit D. Hydroxycarbamide E. Idiopathic myelofibrosis F. Erythropoeitin G. Venesection H. Chlorambucil I. Acute myeloid leukaemia J. Chronic myeloid leukaemia K. Polycythaemia vera L. Imitanib M. Essential thrombocythaemia N. Melphalan O. Tear drop poikilocytes P. Microcytosis

Answer 776

Essential thrombocythaemia

Question 777

A routine medical of 33-year-old footballer reveals: Hb = 9.9g/dl and WCC = 130 x 109/L. His blood film shows whole spectrum of myeloid precursors, including a few blast cells. He admits to having frequent night sweats and blurred vision. There is a presence of Ph chromosome t(9;22) on cytogenetic analysis. A. Lung fibrosis B. Hairy cell leukaemia C. Hypothyroidism D. Septicaemia E. Acute promyelocytic leukaemia F. Chronic myeloid leukaemia G. Acute myeloid leukaemia H. Chronic lymphocytic leukaemia I. Bronchial carcinoma J. DIC K. Vincristine poisoning L. Tumour-lysis syndrome M. Richter's syndrome N. Acute lymphoblastic leukaemia

Answer 777

CML

Question 778

A 5-year-old girl presents with failure to thrive, recurrent fever and bruising. Immunotyping reveals the presence of CD10.. A. Lung fibrosis B. Hairy cell leukaemia C. Hypothyroidism D. Septicaemia E. Acute promyelocytic leukaemia F. Chronic myeloid leukaemia G. Acute myeloid leukaemia H. Chronic lymphocytic leukaemia I. Bronchial carcinoma J. DIC K. Vincristine poisoning L. Tumour-lysis syndrome M. Richter's syndrome N. Acute lymphoblastic leukaemia

Answer 778

ALL

Question 779

The commonest adult leukaemia.

Answer 779

CLL

Question 780

50yr old man presents to his GP complaining of weight loss, tiredness, easy bruising and a painful big toe. On examination his spleen is massively enlarged. Investigation shows a raised serum urate. The peripheral blood film is abnormal, showing proliferation of which type of cell? ## Footnote A. Neutrophils B. Chromosome 9;22 translocation C. Spherocytes D. Pelger-Huet cells E. Blast cells F. Auer rods G. Eosinophils H. Reticulocytes I. Platelets J. Chromosome 11q23 deletion K. Clonal B lymphocytes

Answer 780

Neutrophils CML. Increased mass of turning-over cells generates urate

Question 781

A 70yr old man complains of a year’s history of fatigue, weight loss and recurrent sinusitis. His white cell count is raised with a lymphocytosis of 283x109 /L. Blood film shows features of haemolysis and Coomb’s test is positive. Further investigation show the bone marrow, blood and lymph nodes are infiltrated with which cell population? A. Neutrophils B. Chromosome 9;22 translocation C. Spherocytes D. Pelger-Huet cells E. Blast cells F. Auer rods G. Eosinophils H. Reticulocytes I. Platelets J. Chromosome 11q23 deletion K. Clonal B lymphocytes

Answer 781

Clonal B lymphocytes CLL. Only two chronic B cell leukaemia/lymphomas are CD5+: CLL (CD5+ CD23+) and Mantle Cell Lymphoma (CD5+ CD23-). CLL may be assoc. with Coombs positive AIHA and ITP. The combination is called Evans syndrome.

Question 782

What is a poor prognositc sign in CLL

Answer 782

del 11q23

Question 783

What differntiates between CML and myelodproliferative disorders and infections

Answer 783

Neutrophil ALP is low in CML Raised in myeloproliferative disorders and infections

Question 784

What is the blast threshold in the BM for AML

Answer 784

20%

Question 785

characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors

Answer 785

Refractory anemia (RA)

Question 786

characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called 'ringed sideroblasts'

Answer 786

Refractory anemia with ringed sideroblasts (RARS)

Question 787

characterized by 5-19% myeloblasts in the marrow

Answer 787

Refractory anemia with excess blasts (RAEB)

Question 788

haracterized by 20-29% myeloblasts in the marrow (30% blasts is defined as acute myeloid leukemia in FAB classification but 20% in the WHO classification.. ...therefore a controversial category and the WHO have abandoned teh RAEB-T category!)

Answer 788

Refractory anemia with excess blasts in transformation (RAEB-T)

Question 789

characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 \* 109/uL monocytes circulating in the peripheral blood. Also something that often comes up in exams: - syndrome, typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells.

Answer 789

Chronic myelomonocytic leukemia (CMML) - not to be confused with chronic myelogenous leukemia or CML

Question 790

Female Age at diagnosis: 74 years Transfusion-dependent anemia Normal or increased platelet counts along with bone marrow hyperplasia of hypolobulated micromegakaryocytes

Answer 790

q syndrome, there is a low incidence of thrombocytopenia. These patients may actually have thrombocytosis These patietnts have a low incidence of neutropenia, infection, and bleeding and low incidence of transformation into acute leukemi

Question 791

Treatment of 5q sunydrome

Answer 791

Lenalidomide

Question 792

A 44 year old with recurrent URTI and haematuria in last 6 months presents to GP. He also has a number of mouth ulcers and blood film demonstrates pancytopenia. What treatment would be appropriate? Options Androgen Anti-thymocyte globulin BMT Blood transfusion Corticosteroids Oral Iron Vitamin B12 ANS:Anti-thymocyte globulin I understand this is AA but I'm not quite sure when you would use the different treatment options e.g. corticosteroids, BMT, androgens....

Answer 792

This is covered very well in the lecture you have been given, but essentially - when supportive measures fail, Immune suppression is especially useful if a matched sibling donor for BMT is not available or if the patient is older than 60 years. Bone MArrow transplantation -HLA-matched sibling-donor BMT is the treatment of choice for a young patient with SAA (controversial but generally accepted for age \<60 y). There are no hard and fast rules, and remember that that the cause of aplastic anaemia needs to be elucidated, and treatment may be directed specifically towards the underlying cause.

Question 793

An 83 year old woman presents to the A+E Departments with severe weakness and shortness of breath on minimal exertion. On examination, masses are felt in both left and right upper quadrants of the abdomen.

Answer 793

Myelofibrosis

Question 794

If thrombin time is up

Answer 794

there is a fibrinogen problem.

Question 795

If APTT or PT is up

Answer 795

there is a coagulation factor dysfunction or deficiency.

Question 796

If bleeding time is up

Answer 796

there is a platelet dysfunction or deficiency.

Question 797

To diagnose DIC you need

Answer 797

need low platelets, low fibrinogen, raised APTT and PT, raised D-dimers, schistocytes on blood smear, and a compatible clinical setting.

Question 798

"A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods." Why is this osler weber rendu syndrome and not von willebrand disease?

Answer 798

The key to the question is "mother of 4 children" - vWD would almost certainly have been picked up due to prolonged bleeding during one of these pregnancies/deliveries. OWR is diagnosed by the triad of epistaxis, telangiectasia and a suitable family history. So whilst telangiectasia are not directly mentioned in the question, nosebleeds would suggest OWR as a possibility. As bleeding in OWR is from vascular malformations (caused by mutations in the TGF-B pathway) and not a direct coagulation defect, it would be less likely to be picked up on routine screening in pregnancy. This makes it a better fit in this question than vWD. The only documented associations between OWR and heavy menstrual bleeding are a few case reports suggesting uterine arterio-venous malformations. However this is a very common symptom in the normal population, and many OWR patients will have heavy periods with no relevance to their underlying disease process. The question could be more direct in pointing to OWR, but there is a widely varying phenotype and this is a very possible presentation. In real life you would perform a coagulation screen, take a good family history and you would have the diagnosis.

Question 799

Why is Warfarin always started under Heparin cover

Answer 799

Warfarin alone initially increases the clotting risk because proteins C and S (the anticoagulant proteins) have shorter half lives and disappear from the blood faster than factors II, VII, IX, X (the procoagulant proteins).

Question 800

How can Heparin induced thrombcotyopaenia be classified

Answer 800

Types 1 and 2

Question 801

Type 1 HIT

Answer 801

Dose related effect mediated by platelet aggregation

Question 802

Type 2 HIT

Answer 802

Unpredictable immune response with antibodies directed against the heparin-platelet factor 4 complex Large aggregates cause thrombosis

Question 803

Treatment of HIT T2

Answer 803

Stop heparin and start a direct thrombin inhibiotr e.g. hirudin

Question 804

Which treatment does HIT more commonly following

Answer 804

UFH

Question 805

What is the exception to usual rule that Warfarin is more effective than LMWH?

Answer 805

Cancer

Question 806

Gaucher's disease

Answer 806

a hereditary disease in which the metabolism and storage of fats is abnormal. It results in bone fragility, neurological disturbance, anaemia, and enlargement of the liver and spleen.

Question 807

Spur cell hemolytic anemia

Answer 807

Spur cell hemolytic anemia, is a form of hemolytic anemia that results secondary to severe impaired liver function or cirrhosis. Chronic liver disease impairs the liver's ability to esterify cholesterol, causing free cholesterol to bind to the red cell membrane, increasing its surface area. This condition also creates rough or thorny projections on the erythrocyte named acanthocytes. [

Question 808

A 10 year old boy presenting with tan-to-grey hyperpigmented patches on his upper trunk, neck and face, nail ridges and leukoplakia. A. Dyskeratosis congenita B. Hepatitis C infection C. Parvovirus B19 infection D. Aplastic anaemia E. Fanconi anaemia F. Myelofibrosis G. Drug-induced H. Radiation-induced I. Acute myeloid leukaemia J. Systemic lupus erythematosus

Answer 808

Dyskeratosis congenita is characterised by a triad of Nail dystrophy, leukoplakia and cutaneous manifestations.

Question 809

A 76 year old man presents to his GP with increasing tiredness, weakness and a long-standing cold. The blood results ordered by the GP showed that the gentleman was anaemic and that increased blast cells were present. A. Dyskeratosis congenita B. Hepatitis C infection C. Parvovirus B19 infection D. Aplastic anaemia E. Fanconi anaemia F. Myelofibrosis G. Drug-induced H. Radiation-induced I. Acute myeloid leukaemia J. Systemic lupus erythematosus

Answer 809

AML

Question 810

An 83 year old woman presents to the A&E Departments with severe weakness and shortness of breath on minimal exertion. On examination, masses are felt in both left and right upper quadrants of the abdomen. Blood film show leukoerythroblastic cells and teardrop poikilocytes. A. Dyskeratosis congenita B. Hepatitis C infection C. Parvovirus B19 infection D. Aplastic anaemia E. Fanconi anaemia F. Myelofibrosis G. Drug-induced H. Radiation-induced I. Acute myeloid leukaemia J. Systemic lupus erythematosus

Answer 810

Myelofibrosis

Question 811

A 19 year old Jewish male presenting with multiple pathological fractures and hypersplenism. A. Paroxysmal nocturnal haemoglobinuria B. Sepsis C. Autoimmune haemolytic anaemia D. Pyruvate kinase deficiency E. Hereditary spherocytosis F. Sickle-cell disease G. Cardiac haemolysis H. Spur cell anaemia I. Drug-induced immune haemolysis J. Gaucher's disease (glucosylceramide lipidosis) K. Hereditary elliptocytosis L. Haemolytic uraemic syndrome

Answer 811

Gaucher's

Question 812

A 26 year old primary school teacher presents with chronic anaemia. She has an increased (unconguated) bilirubin, and has had well controlled systemic lupus erythematosus for 7 years. A. Paroxysmal nocturnal haemoglobinuria B. Sepsis C. Autoimmune haemolytic anaemia D. Pyruvate kinase deficiency E. Hereditary spherocytosis F. Sickle-cell disease G. Cardiac haemolysis H. Spur cell anaemia I. Drug-induced immune haemolysis J. Gaucher's disease (glucosylceramide lipidosis) K. Hereditary elliptocytosis L. Haemolytic uraemic syndrome

Answer 812

AIHA

Question 813

A 35 year old women complains of abdominal pain. There is associated pancytopenia, and a Ham’s test is positive. A. Paroxysmal nocturnal haemoglobinuria B. Sepsis C. Autoimmune haemolytic anaemia D. Pyruvate kinase deficiency E. Hereditary spherocytosis F. Sickle-cell disease G. Cardiac haemolysis H. Spur cell anaemia I. Drug-induced immune haemolysis J. Gaucher's disease (glucosylceramide lipidosis) K. Hereditary elliptocytosis L. Haemolytic uraemic syndrome

Answer 813

PNH

Question 814

A woman aged 69 with no past medical history except osteoarthritis suffered acute haemolysis after her right hip was replaced. There was no evidence of splenomegaly or lymphadenopathy and both warm and cold antibody tests were negative. When she had the left hip replaced 2 years later she again developed haemolysis soon after the anaesthetic. She was tested for IgG and IgE antibodies to the anaesthetic. Seven months later she had a revision arthroplasty and haemolysed again. Which condition might she have? A. Sickle cell anaemia B. Paroxysmal cold haemoglobinuria C. Primary autoimmune haemolytic anaemia D. Paroxysmal nocturnal haemoglobinuria E. Cephalosporin-induced haemolytic anaemia F. Hereditary elliptocytosis G. G6PD deficiency H. Autoimmune haemolytic anaemia due to infectious mononucleosis I. Hereditary spherocytosis J. Disseminated intravascular coagulation K. Sepsis

Answer 814

Cephalosporin-induced haemolytic anaemia

Question 815

In which condition might the sucrose and Ham acid haemolysis tests be positive?

Answer 815

PNH

Question 816

Mr RX came to Fulham from Thailand last year. He has inflammatory bowel disease and is taking dapsone for his dermatitis herpetiformis. Which of the above conditions would be likely and clinically relevant? A. Sickle cell anaemia B. Paroxysmal cold haemoglobinuria C. Primary autoimmune haemolytic anaemia D. Paroxysmal nocturnal haemoglobinuria E. Cephalosporin-induced haemolytic anaemia F. Hereditary elliptocytosis G. G6PD deficiency H. Autoimmune haemolytic anaemia due to infectious mononucleosis I. Hereditary spherocytosis J. Disseminated intravascular coagulation K. Sepsis

Answer 816

Dapsone is used to treat dermatitis herpetiformis. Dapsone is known to cause haemolysis in G6PD deficient patients, so it is avoided. G6PD deficiency in commoner in Thai people.

Question 817

A 29 year old man noticed he had yellow eyes and dark urine. He was always tired, and could not take part in sports as he easily became short of breath. There was no itching, fever or bleeding, and he was not taking any drugs. On examination he was anaemic, jaundiced, afebrile and had no palpable lymphadenopathy, hepatosplenomegaly or rash. His blood tests showed Hb 5.4g/Dl and raised WCC (40 x 109/L), bilirubin (47 µmol/l), aspartate transaminase (90iu/L) and lactate dehydrogenase (5721iu/l). The blood film showed polychromic nucleated red cells and spherocytes and the reticulocyte count was 9%. Direct Coombs' test revealed IgG and C3 on the red cell surfaces. The serum contained a warm non-specific autoantibody (i.e. it reacted with all the red cells in the test panel). Antinuclear antibodies and rheumatoid factor tests were negative and immunoglobulin levels were normal; there were no paraprotein bands in his serum. He failed to respond to high-dose corticosteroids and had a splenectomy three weeks later. A. Sickle cell anaemia B. Paroxysmal cold haemoglobinuria C. Primary autoimmune haemolytic anaemia D. Paroxysmal nocturnal haemoglobinuria E. Cephalosporin-induced haemolytic anaemia F. Hereditary elliptocytosis G. G6PD deficiency H. Autoimmune haemolytic anaemia due to infectious mononucleosis I. Hereditary spherocytosis J. Disseminated intravascular coagulation K. Sepsis

Answer 817

Primary AIHA

Question 818

In which condition might a Donath-Landsteiner be positive?

Answer 818

Paroxysmal cold haemoglobinuria

Question 819

A 28 year old female presents with fever \< 40 C and rigors approx. 1 ½ hours after transfusion. She has two children and previously had a blood transfusion 7 years ago.

Answer 819

Febrile non haemolytic transfusion reaction Febrile non-haemolytic transfusion reaction (FNHTR) is an immediate reaction, causing fever and rigors. In contrast, delayed haemolytic transfusion reaction (DHTR) manifests days to weeks after a transfusion, acommpanied by a falling haemoglobin and jaundice or haemoglobinuria. Bacterial contamination can present in a similar manner to FNHTR but is differentiated by a much more marked fever; in addition, profound hypotension and tachycardia may occur.

Question 820

A 44 year old male develops a pyrexia of \>40 C and marked hypotension very shortly after receiving a blood transfusion. He has never had a transfusion before and there is no evidence of ABO blood group / rhesus incompatibility. A. Anaphylactic reaction B. Fluid overload C. TRALI D. Graft versus host disease E. Bacterial contamination F. Delayed haemolytic transfusion reaction. G. Viral contamination H. Allergic reaction I. Febrile non haemolytic transfusion reaction J. Immediate haemolytic transfusion reaction K. Iron overload

Answer 820

Bacterial contamination

Question 821

n 18 year old boy with sickle cell anaemia is observed to have short stature. Further tests reveal poor cardiac function A. Anaphylactic reaction B. Fluid overload C. TRALI D. Graft versus host disease E. Bacterial contamination F. Delayed haemolytic transfusion reaction. G. Viral contamination H. Allergic reaction I. Febrile non haemolytic transfusion reaction J. Immediate haemolytic transfusion reaction K. Iron overload

Answer 821

Fe overload

Question 822

An 18 year old African girl known to suffer from sickle cell anaemia develops a fever, sudden lethargy, pallor and arthralgia two months post-transfusion. Investigations reveal bone marrow red cell aplasia and a positive Paul-Bunnell test. A. CMV infection B. Post-transfusion purpura (PTP) C. Immunological haemolytic reaction D. Non-haemolytic reaction E. Delayed haemolytic transfusion reaction (DHTR) F. Transfusion-related acute lung injury (TRALI) G. Allergic reaction to transfusion H. Graft vs. Host disease (GvHD) I. Iron overload J. Reaction to massive transfusion K. Air embolism L. Transfusion-related fluid overload M. B19 parvovirus infection

Answer 822

B19 parvovirus infection

Question 823

A 32 year old Irish man was noted to have a temperature of 36.9ºC and blood electrolyte results of: urea = 5.2 mmol/L, sodium = 144 mmol/L, potassium = 5.5 mmol/L, calcium = 2.5 mmol/L after receiving 10 units of blood over a 24 hour period. A. CMV infection B. Post-transfusion purpura (PTP) C. Immunological haemolytic reaction D. Non-haemolytic reaction E. Delayed haemolytic transfusion reaction (DHTR) F. Transfusion-related acute lung injury (TRALI) G. Allergic reaction to transfusion H. Graft vs. Host disease (GvHD) I. Iron overload J. Reaction to massive transfusion K. Air embolism L. Transfusion-related fluid overload M. B19 parvovirus infectio

Answer 823

Reaction to massive transfusion

Question 824

A 55 year old British female developed an itchy, diffuse erythematous rash on both arms fifteen minutes after receiving a blood transfusion. This rash responded well to acrivastine. A. CMV infection B. Post-transfusion purpura (PTP) C. Immunological haemolytic reaction D. Non-haemolytic reaction E. Delayed haemolytic transfusion reaction (DHTR) F. Transfusion-related acute lung injury (TRALI) G. Allergic reaction to transfusion H. Graft vs. Host disease (GvHD) I. Iron overload J. Reaction to massive transfusion K. Air embolism L. Transfusion-related fluid overload M. B19 parvovirus infection

Answer 824

Allergic reaction to transfusion

Question 825

Patient develops shortness of breath, dry cough and chills. Donors blood was found to contain anti-leucocyte antibodies with similar specificity to the patient’s white blood cell antigens. A. Iron overload B. TA-GVHD – Transfusion associated graft versus host disease C. Bacterial infection D. ABO incompatible E. DHTR – Delayed Haemolytic transfusion reaction F. IgA deficiency G. FNHTR – Febrile non-haemolytic transfusion reaction H. TRALI – Transfusion related acute lung injury I. Urticarial rash

Answer 825

TRALI

Question 826

Patient has a severe anaphylactic reaction soon after transfusion. Signs and symptoms include wheeze, raised pulse, low blood pressure and laryngeal oedema. A. Iron overload B. TA-GVHD – Transfusion associated graft versus host disease C. Bacterial infection D. ABO incompatible E. DHTR – Delayed Haemolytic transfusion reaction F. IgA deficiency G. FNHTR – Febrile non-haemolytic transfusion reaction H. TRALI – Transfusion related acute lung injury I. Urticarial rash

Answer 826

IgA deficiency

Question 827

A 40 year old male patient with known Sickle-Cell anaemia develops mild symptoms of fever and rigors 3 to 4 days after a transfusion. A. Transfursion related acute lung injury B. CMV infection C. Anaphylaxis due to IgA deficiency D. Delayed transfusion reaction E. Febrile non-haemolytic transfusion reaction F. Post-transfusion purpura G. Air embolism H. Iron overload I. ABO incompatible J. Graft vs host disease K. Urticarial rash L. Bacterial infection

Answer 827

Febrile non-haemolytic transfusion reaction

Question 828

A 24 year old male who was diagnosed with thalassaemia major at 13 months presents to outpatients clinic complaining of malaise and erectile dysfunction. A. Delayed haemolytic transfusion reaction (DHTR) B. Kleihauer test C. Viral contamination of transfusion D. Pulmonary embolism E. Guthrie test F. Bacterial contamination of transfusion G. Immediate haemolytic transfusion reaction H. Transfusion haemosiderosis I. Transfusion-related acute lung injury (TRALI) J. Allergic reaction to forein protein in donor blood

Answer 828

Transfusion haemosiderosis

Question 829

A 25 year old man vomits and becomes restless on receiving a blood transfusion, he also complains of chest and abdominal pain. A. TRALI B. Post-transfusion purpura C. Delayed haemolytic transfusion reaction D. Fungal infection E. Pulmonary Embolism F. Iatrogenic Iron overload G. Allergic reaction H. Bacterial infection I. Viral infection J. Immediate haemolytic transfusion reaction K. Transfusion-associated graft versus host disease L. Massive transfusion reaction M. Air Embolism

Answer 829

Immediate haemolytic transfusion reaction

Question 830

A 60 year old man who has been given a blood transfusion has noticed an itchy rash on his arms and legs. A. TRALI B. Post-transfusion purpura C. Delayed haemolytic transfusion reaction D. Fungal infection E. Pulmonary Embolism F. Iatrogenic Iron overload G. Allergic reaction H. Bacterial infection I. Viral infection J. Immediate haemolytic transfusion reaction K. Transfusion-associated graft versus host disease L. Massive transfusion reaction M. Air Embolism

Answer 830

Allergic reaction

Question 831

Pathophysiology of FNHTR

Answer 831

FNHTR is thought to be caused by the reaction between leukocyte antibodies present in the plasma of a recipient reacting against leukocytes present in transfused (donor) red cells. However, platelet associated FNHTR seems to be related to the presence of pyrogenic cytokines released from leukocytes during the platelet storage. Leukoreduction (i.e. removal of white cells prior to transfusion) of the cellular blood components may effectively reduce the occurrence of FNHTR.

Question 832

Difference between TRALI and TA-GvD

Answer 832

TRALI occurs if the donor's plasma contains white cell antibodies incompatible with the recipient's white cells. TRALI is characterised by chills, fever, dry cough and breathlessness with cardiac failure. TA-GvD is a rare complication in which donor T lymphocytes mount a response against the recipient's lymphoid tissue. Typical symptoms include fever and erythematous macular papular rash. Other symptoms include cough, abdominal pain, vomiting and profuse diarrhoea.

Question 833

Which Ab mediates cold autoimmune haemolysis

Answer 833

IgM

Question 834

What can lead to cold-Ab mediated haemolysis

Answer 834

May be polycolonal and arise as a result of infection e.g. mycoplasma pneumonia or infectious mononucleosis It can also be monoclonal, secondary to lymphoma

Question 835

Pathophysiology of cold AIHA

Answer 835

In COLD-antibody mediated haemolysis, the Ab (usually IgM) may be polyclonal and arise as a result of infection (e.g mycoplasma pneumonia or infectious mononucleosis) or may be monoclonal secondary to a lymphoproliferative disorder (e.g. Non-Hodgekins Lymphoma). The red cells become coated with IgM antibodies in the cooler peripheral circulation. Complement is activated at slightly higher temperatures, resulting in intravascular haemolysis. IgM is detectable on the red cells at 4 deg C. At higher temperatures, IgM detaches from the red cell surface but complement can still be detected. Circulating free cold autoantibodies - cold agglutins - are also present in the patients serum. A direct Coombs' test may be positive for complement (but not for antibodies, as the IgM antibodies elute from the red cell into the serum in vitro). In addition to cold avoidance, other Rx options include drugs such as chlorambucil.

Question 836

Which Abs are associated with warma AIHA

Answer 836

IgG

Question 837

With what conditions is warm AIHA associated?

Answer 837

0% of cases are idiopathic, but other associations include autoimmune diseases eg. SLE, or drugs.

Question 838

Pathophysiology of warm AIHA

Answer 838

WARM autoimmune haemolytic anaemias are associated with IgG antibodies to red blood cells. These antibodies react best at body temperature. 50% of cases are idiopathic, but other associations include autoimmune diseases eg. SLE, or drugs. Red cells are opsonised with either antibody alone, or antibody and complement components, and subsequently removed by splenic macrophages. The patient's red cells are direct Coombs' test positive; they promptly agglutinate when mixed with antiglobulin reagent. Rx may be steroids or splenectomy.

Question 839

How does PRV cause a low ferritin

Answer 839

the Hb, WBC and platelet counts would be raised together with a low ferritin. Ferritin falls because of the increased demand for iron due to increased haematopoesis.

Question 840

An 18 year old African girl known to suffer from sickle cell anaemia develops a fever, sudden lethargy, pallor and arthralgia two months post-transfusion. Investigations reveal bone marrow red cell aplasia and a positive Paul-Bunnell test.

Answer 840

infection with erythrovirus (parvovirus) B19 may result in a false positive Paul Bunnell test'. PS. The red cell aplasia with haemoglobinopathy gives it away that its Parvovirus B19. Normally, we would mount a reticulocyte response and be assymptomatic (or slapped cheek in children), but sickle cell = reduced red cell lifespan, reticulocytopenia and marrow aplasia = crisis!!

Question 841

Found in patients with Myeloma with low serum albumin and oedema. A. Bence-Jones proteins B. Extramedullary tumour deposits C. Paraprotein D. Amyloid E. Inflammation F. Osteoblasts G. Barry-Jane proteins H. Osteoclasts

Answer 841

Amyloid

Question 842

Misfolded protein deposited in myeloma-associated amyloidosis A. Interferon α + ibuprofen B. Lenalidomide + low dose dexamethasone C. Melphalan + prednisolone D. Infliximab + budesonide E. Monoclonal gammopathy of undetermined significance (MGUS) F. AL amyloid G. IgM H. Multiple myeloma I. Thalidomide + high dose dexamethasone J. Bortezomib K. Rituximab L. Waldenstrom’s macroglobinaemia M. AA amyloid N. Aβ amyloid O. Anaemia & renal failure

Answer 842

AL amyloid

Question 843

How can treatment of myeloma be categroised

Answer 843

Into those sutiable for auto-SCT and those who are not

Question 844

Treatment of a patient with MM unsuitable for auto-SCT

Answer 844

Melphalan + Pred + thalidomide= first line Melphalan + pred + bortezomib= second line ( can't tolerate thalidomide)

Question 845

Treatment of MM in patient sutiable for SCT

Answer 845

Use induction chemo: Lenalidomide + Dex =first line Bortezomib + dex= second line Alkylating agents e.g. mephalan are best avoided for induction chemo as they may compromise SC reserve

Question 846

Asymptomatic, serum monoclonal protein 10g/L, marrow plasma cells 15%, serum Ca 2.3 mmol/L, estimated GFR 30 mL/min, Hb 8 g/dL, lytic vertebral lesions A. Primary hyperparathyroidism B. Waldenstrom's macroglobulinaemia C. MGUS D. Sarcoidosis E. Solitary plasmacytoma of bone (SPB) F. Metastatic breast cancer G. Primary amyloidosis H. Secondary hyperparathyroidism I. CLL J. Multiple myeloma K. Smouldering multiple myeloma

Answer 846

MM

Question 847

Previously fit 35yo Afro Carribean female, sudden onset back pain, no history of trauma, 1 month history polyuria, urine specific gravity raised but dipstick negative for protein (and normal in all other respects), estimated GFR 70mL/min, vertebral fracture and bilateral femoral neck fractures on radiograph A. Primary hyperparathyroidism B. Waldenstrom's macroglobulinaemia C. MGUS D. Sarcoidosis E. Solitary plasmacytoma of bone (SPB) F. Metastatic breast cancer G. Primary amyloidosis H. Secondary hyperparathyroidism I. CLL J. Multiple myeloma K. Smouldering multiple myeloma .

Answer 847

MM

Question 848

Asymptomatic, serum monoclonal protein 25g/L, marrow plasma cells 5%, serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal A. Primary hyperparathyroidism B. Waldenstrom's macroglobulinaemia C. MGUS D. Sarcoidosis E. Solitary plasmacytoma of bone (SPB) F. Metastatic breast cancer G. Primary amyloidosis H. Secondary hyperparathyroidism I. CLL J. Multiple myeloma K. Smouldering multiple myeloma

Answer 848

MGUS

Question 849

Asymptomatic, serum monoclonal protein 30g/L, marrow plasma cells 10%, serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal A. Primary hyperparathyroidism B. Waldenstrom's macroglobulinaemia C. MGUS D. Sarcoidosis E. Solitary plasmacytoma of bone (SPB) F. Metastatic breast cancer G. Primary amyloidosis H. Secondary hyperparathyroidism I. CLL J. Multiple myeloma K. Smouldering multiple myeloma

Answer 849

Smouldering multiple myeloma

Question 850

Which paraprotein is most commonly raised in patients with multiple myeloma?

Answer 850

IgG

Question 851

Which cytokine is an important growth factor in the development of myeloma?

Answer 851

IL-6

Question 852

Elevated levels imply a poor prognosis in myeloma patients

Answer 852

Beta a2 microglobulin

Question 853

How is MM staged

Answer 853

Using the international staging system Uses beta 2 microglobulin and albumin to stage a patient's disease Age and cytogenetics are the only other factors that impact on Px

Question 854

A 65 yr old man presents to his GP with general malaise, weight loss and visual disturbances that he likens to looking through a watery car windscreen. On examination he has peripheral lymph node enlargement. Protein electrophoresis shows an IgM paraprotein. A. Metastatic carcinoma B. Multiple myeloma C. Monoclonal gammopathy of undetermined significance D. Chronic lymphocytic leukaemia E. Secondary amyloidosis F. Waldenstrom's macroglobulinaemia G. Primary amyloidosis

Answer 854

Waldenstrom's macroglobulinaemia is a malignant disease of B cells which are lymphoplasmacytoid in appearance. These cells secrete IgM paraprotein which gives rise to clinical manifestations. The disease is commonly seen in elderly men. It is an indolent disease with a median survival of 3 to 5 years, but some patients may survive 10 years or longer. It is regarded as a low grade non-Hodgkin's lymphoma.

Question 855

A 49-year-old woman presented with a 6-month history of vague aches and pains in her chest. On examination, she was overweight but had no abnormal physical signs. Protein electrophoresis showed a small paraprotein band in the gamma region; this band was an IgG of lambda type. A bone marrow biopsy showed only 12% plasma cells. There was no protein in her urine. A. Non-Hodgkin's lymphoma B. Hairy cell leukaemia C. Sarcoidosis D. Acute leukaemia E. Multiple myeloma F. Hodgkin's lymphoma G. Bone metastasis H. Fractured vertebrae I. Sezary syndrome J. Benign paraproteinaemia

Answer 855

Benign paraproteinaemia

Question 856

A 71-year-old man presented with sharp, constant, low back pain, dating from a fall from a ladder 6 weeks earlier. He admitted to vague malaise for over 8 months. He had a raised serum calcium level (3.2mmol/l) but a normal alkaline phosphatase. X-rays of his back showed a small, punched-out lesion in the second lumbar vertebra and a Bone marrow biopsy showed an increased number of atypical plasma cells; these constituted 45% of the nucleated cells found on the film. A. Non-Hodgkin's lymphoma B. Hairy cell leukaemia C. Sarcoidosis D. Acute leukaemia E. Multiple myeloma F. Hodgkin's lymphoma G. Bone metastasis H. Fractured vertebrae I. Sezary syndrome J. Benign paraproteinaemia

Answer 856

Multiple myeloma

Question 857

A 43 year old man presents to his GP with concerns over a tender lump on the left side of his abdomen. Investigation showed a normal haemoglobin but a mildly raised white-cell count (13.2 x 109/l). On the blood film these cells were mainly small mononuclear cells resembling lymphocytes. These cells stained positively for tartrate-resistant acid phosphatase. A. Non-Hodgkin's lymphoma B. Hairy cell leukaemia C. Sarcoidosis D. Acute leukaemia E. Multiple myeloma F. Hodgkin's lymphoma G. Bone metastasis H. Fractured vertebrae I. Sezary syndrome J. Benign paraproteinaemia

Answer 857

Hairy cell leukaemia

Question 858

A 69 year old man presents with a complaint of right elbow pain. Radiography shows a lytic lesion in the area of the right proximal radius. Biopsy of the lesion reveals a mono-clonal population of plasma cells consistent with a plasmacytoma. A radiographic skeletal bone survey shows other similar lesions. A. Non-Hodgkin's lymphoma B. Hairy cell leukaemia C. Sarcoidosis D. Acute leukaemia E. Multiple myeloma F. Hodgkin's lymphoma G. Bone metastasis H. Fractured vertebrae I. Sezary syndrome J. Benign paraproteinaemia

Answer 858

MM

Question 859

Corticosteroid refractory haemolytic anaemia

Answer 859

Splenectomy

Question 860

Chronic lymphocytic leukaemia A. Folate B. Thymectomy C. Splenectomy D. Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT) E. Anagrelide F. Campath (anti CD52, alemtuzumab) G. Imatinib H. Regular surveillance but no active treatment I. Bortezomib (Velcade) J. Venesection and aspirin K. Hydroxyurea L. Rituximab (anti CD20) M. Leucovorin (Folinic acid, Formyl tetrahydrofolate) N. Treatment with anti lymphocyte globulin O. Cyclophosphamide, fludarabine and rituximab P. Dexamethasone alone Q. Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT) R. Thalidomide and dexamethasone S. Melphalan

Answer 860

Cyclophosphamide, fludarabine and rituximab

Question 861

Chronic myeloid leukaemia (also known as chronic granulocytic leukaemia) A. Folate B. Thymectomy C. Splenectomy D. Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT) E. Anagrelide F. Campath (anti CD52, alemtuzumab) G. Imatinib H. Regular surveillance but no active treatment I. Bortezomib (Velcade) J. Venesection and aspirin K. Hydroxyurea L. Rituximab (anti CD20) M. Leucovorin (Folinic acid, Formyl tetrahydrofolate) N. Treatment with anti lymphocyte globulin O. Cyclophosphamide, fludarabine and rituximab P. Dexamethasone alone Q. Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT) R. Thalidomide and dexamethasone S. Melphalan

Answer 861

Imatinib

Question 862

Multiple myeloma A. Folate B. Thymectomy C. Splenectomy D. Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT) E. Anagrelide F. Campath (anti CD52, alemtuzumab) G. Imatinib H. Regular surveillance but no active treatment I. Bortezomib (Velcade) J. Venesection and aspirin K. Hydroxyurea L. Rituximab (anti CD20) M. Leucovorin (Folinic acid, Formyl tetrahydrofolate) N. Treatment with anti lymphocyte globulin O. Cyclophosphamide, fludarabine and rituximab P. Dexamethasone alone Q. Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT) R. Thalidomide and dexamethasone S. Melphalan

Answer 862

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

Question 863

Treatment of MGUS and smouldering myeloma

Answer 863

Regular surveillance but no active treatment

Question 864

Used in solid organ transplantation, multiple sclerosis, NHL. Depletes lymphocytes. Side effects include ITP and Graves disease. A. Folate B. Thymectomy C. Splenectomy D. Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT) E. Anagrelide F. Campath (anti CD52, alemtuzumab) G. Imatinib H. Regular surveillance but no active treatment I. Bortezomib (Velcade) J. Venesection and aspirin K. Hydroxyurea L. Rituximab (anti CD20) M. Leucovorin (Folinic acid, Formyl tetrahydrofolate) N. Treatment with anti lymphocyte globulin O. Cyclophosphamide, fludarabine and rituximab P. Dexamethasone alone Q. Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT) R. Thalidomide and dexamethasone S. Melphalan

Answer 864

Campath (anti CD52, alemtuzumab)

Question 865

Add-on anti-proteasome drug for myeloma

Answer 865

Bortezomib (Velcade)

Question 866

Anti-proliferative used in polycythaemia rubra vera and essential thrombocythaemia

Answer 866

Hydroxyurea

Question 867

Reduces platelet count in thrombocythaemia but causes palpitations, tachycardia, fluid retention

Answer 867

Anagrelide

Question 868

Standard prophylaxis accompanying a once weekly myelosuppressant when used in rheumatoid arthritis

Answer 868

Folate

Question 869

Rescue drug after high dose methotrexate is used for gestational trophoblastic disease or intrathecal ALL

Answer 869

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

Question 870

Used in solid organ transplantation, multiple sclerosis, NHL. Depletes B lymphocytes more than T lymphocytes. A. Folate B. Thymectomy C. Splenectomy D. Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT) E. Anagrelide F. Campath (anti CD52, alemtuzumab) G. Imatinib H. Regular surveillance but no active treatment I. Bortezomib (Velcade) J. Venesection and aspirin K. Hydroxyurea L. Rituximab (anti CD20) M. Leucovorin (Folinic acid, Formyl tetrahydrofolate) N. Treatment with anti lymphocyte globulin O. Cyclophosphamide, fludarabine and rituximab P. Dexamethasone alone Q. Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT) R. Thalidomide and dexamethasone S. Melphalan

Answer 870

Rituximab (anti CD20)

Question 871

Myeloma A. Variable B cell B. Indolent B cell C. Aggressive B cell D. Variable T cell E. Aggressive T cell F. Indolent T cell

Answer 871

Variable B cell

Question 872

Most easily curable B cell neoplasm A. Variable B cell B. Indolent B cell C. Aggressive B cell D. Variable T cell E. Aggressive T cell F. Indolent T cell

Answer 872

Aggressive B cell

Question 873

Follicular lymphoma A. Variable B cell B. Indolent B cell C. Aggressive B cell D. Variable T cell E. Aggressive T cell F. Indolent T cell

Answer 873

Indolent B cell

Question 874

An elderly lady is found to suffer from Epstein-Barr virus. She is late noted to have splenic enlargement. A. Multiple Myeloma B. Hairy Cell Leukaemia C. Radiation Therapy Alone D. Aplastic Anaemia E. Chronic Lymphocytic Leukaemia F. Acute Myeloid Leukaemia G. Polycythaemia Rubra Vera H. Combination Chemotherapy I. ABVD combination chemotherapy + radiotherapy if required J. Hodgkins Stage IIA K. Myelodysplasia L. Hodgkins Disease Stage IB M. Burkitts Lymphoma N. Primary Amyloidosis

Answer 874

Burkitts Lymphoma

Question 875

Advanced Hodgkins disease should be treated with….. A. Multiple Myeloma B. Hairy Cell Leukaemia C. Radiation Therapy Alone D. Aplastic Anaemia E. Chronic Lymphocytic Leukaemia F. Acute Myeloid Leukaemia G. Polycythaemia Rubra Vera H. Combination Chemotherapy I. ABVD combination chemotherapy + radiotherapy if required J. Hodgkins Stage IIA K. Myelodysplasia L. Hodgkins Disease Stage IB M. Burkitts Lymphoma N. Primary Amyloidosis

Answer 875

Combination chemotherapy

Question 876

Pathological stage IA or IIA disease may be treated with...... A. Multiple Myeloma B. Hairy Cell Leukaemia C. Radiation Therapy Alone D. Aplastic Anaemia E. Chronic Lymphocytic Leukaemia F. Acute Myeloid Leukaemia G. Polycythaemia Rubra Vera H. Combination Chemotherapy I. ABVD combination chemotherapy + radiotherapy if required J. Hodgkins Stage IIA K. Myelodysplasia L. Hodgkins Disease Stage IB M. Burkitts Lymphoma N. Primary Amyloidosis

Answer 876

ABVD combination chemotherapy + radiotherapy if required is an oncogenic virus and may be associated with Burkitt's Lymphoma and nasopharygeal carcinoma. Q5: Treatment for Stage I + II Hodgkin's Lymphoma used to be combined chemo + radiotherapy, but radiotherapy is dangerous in that it increases risk of secondary malignancies eg breast cancer and end-organ damage eg heart disease leading to deaths by MI, stroke, CHF. Reducing the field treated with radiotherapy reduces but does not eliminate these risks. One large review (DOI 10.1007/s11899-011-0088-8) says 'Most young patients with non-bulky, localised, early-stage disease do extremely well on chemotherapy alone'. There are a number of trials currently looking at how to better identify the patients for whom the benefits of radiotherapy would out-weigh the risks.

Question 877

A subtype of Non-Hodgkin lymphoma associated with very aggressive disease. A. Night sweats B. Hodgkin lymphoma C. Aggressive D. Follicular lymphoma E. Stage IIIB F. Stage IIA G. Pruritis H. Non-Hodgkin lymphoma I. Very aggressive J. Diffuse large B cell lymphoma K. Indolent L. Burkitt's lymphoma M. Epstein-Barr virus N. Pel-Ebstein fever

Answer 877

Burkitt's lymphoma

Question 878

A classical but rare constitutional symptom of Hodgkin lymphoma A. Night sweats B. Hodgkin lymphoma C. Aggressive D. Follicular lymphoma E. Stage IIIB F. Stage IIA G. Pruritis H. Non-Hodgkin lymphoma I. Very aggressive J. Diffuse large B cell lymphoma K. Indolent L. Burkitt's lymphoma M. Epstein-Barr virus N. Pel-Ebstein fever

Answer 878

A Pel Ebstein fever is one which has periods of high temperature separated by 15 to 28 day periods of normal temperature. Classically associated with Hodgekins lymphoma. Other differentials include tuberculosis and renal adenocarcinoma. Some physicians believe Pel-Ebstein fever doesn't actually exist! For more information, see attached file.

Question 879

A 61 year old lady complains to her GP of morning stiffness and aching in her hips. She also suffers from anorexia, fatigue and occasional night sweats. She is found to have a raised ESR. Of note she has had giant cell arterititis in the past. What is the most likely diagnosis from the list above. A. Eosinophils B. Anaemia of chronic disease C. Microangiopathic haemolytic anaemia D. Monocytes E. Systemic lupus erythematosis F. Rheumatoid arthritis G. Polymyalgia rheumatica H. Iron deficiency anaemia I. Leucoerythroblastic anaemia J. Diverticular disease K. Neutrophils

Answer 879

Polymyalgia rheumatica

Question 880

An 81 year old man with known prostatic carcinoma presents to his GP with severe bone pain. Blood tests reveal a mild anaemia and peripheral blood film shows nucleated red blood cells and immature myeloid cells. What are these haematological features collectively known as? A. Eosinophils B. Anaemia of chronic disease C. Microangiopathic haemolytic anaemia D. Monocytes E. Systemic lupus erythematosis F. Rheumatoid arthritis G. Polymyalgia rheumatica H. Iron deficiency anaemia I. Leucoerythroblastic anaemia J. Diverticular disease K. Neutrophils

Answer 880

Leucoerythroblastic anaemia

Question 881

A 51 year old man is having work up for palliative surgery due to gastric adenocarcinoma. He is found to be anaemic, with high a reticulocyte count and fragmented red blood cells on blood smear. What is this anaemia known as? A. Eosinophils B. Anaemia of chronic disease C. Microangiopathic haemolytic anaemia D. Monocytes E. Systemic lupus erythematosis F. Rheumatoid arthritis G. Polymyalgia rheumatica H. Iron deficiency anaemia I. Leucoerythroblastic anaemia J. Diverticular disease K. Neutrophils

Answer 881

Microangiopathic haemolytic anaemia

Question 882

A 21 year old student recently returning from India complains to his GP of cough, headache and diarrhoea. He is febrile and rose spots are present on his chest. Blood culture reveals salmonella typhi. Which immune cells out of the list are most likely to be raised? A. Eosinophils B. Anaemia of chronic disease C. Microangiopathic haemolytic anaemia D. Monocytes E. Systemic lupus erythematosis F. Rheumatoid arthritis G. Polymyalgia rheumatica H. Iron deficiency anaemia I. Leucoerythroblastic anaemia J. Diverticular disease K. Neutrophils

Answer 882

Monocytes

Question 883

A markedly raised haemoglobin in a patient with renal cell carcinoma. ## Footnote A. Microangiopathic haemolytic anaemia B. Leucoerythroblastic anaemia C. Type 1 hypersensitivity reaction D. Secondary true polycythaemia E. Autoimmune haemolytic anaemia F. Rheumatoid arthritis G. Polycythaemia vera H. Parasitic infestation I. Brucella infection J. Acute fungal infection

Answer 883

Secondary true polycythaemia

Question 884

Monocytosis but with a normal neutrophil count. ## Footnote A. Microangiopathic haemolytic anaemia B. Leucoerythroblastic anaemia C. Type 1 hypersensitivity reaction D. Secondary true polycythaemia E. Autoimmune haemolytic anaemia F. Rheumatoid arthritis G. Polycythaemia vera H. Parasitic infestation I. Brucella infection J. Acute fungal infection

Answer 884

Brucella infection

Question 885

A markedly raised haemoglobin in a patient with splenomegaly ## Footnote A. Microangiopathic haemolytic anaemia B. Leucoerythroblastic anaemia C. Type 1 hypersensitivity reaction D. Secondary true polycythaemia E. Autoimmune haemolytic anaemia F. Rheumatoid arthritis G. Polycythaemia vera H. Parasitic infestation I. Brucella infection J. Acute fungal infection

Answer 885

Polycythaemia vera

Question 886

Neutrophilia with visible toxic granulation and vacuoles on the blood film. The monocyte count is normal. ## Footnote A. Microangiopathic haemolytic anaemia B. Leucoerythroblastic anaemia C. Type 1 hypersensitivity reaction D. Secondary true polycythaemia E. Autoimmune haemolytic anaemia F. Rheumatoid arthritis G. Polycythaemia vera H. Parasitic infestation I. Brucella infection J. Acute fungal infection

Answer 886

Acute fungal infection

Question 887

Sezary syndrome

Answer 887

Sézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions

Question 888

Prolonged APTT Normal PT Normal bleeding time normal vWF

Answer 888

Haemophilia

Question 889

Prolonged APTT Prolonged bleedeing time Low vWF (normal in VWD2- functional abnormality) Factor VIII levels may also be low

Answer 889

vWD

Question 890

A young boy is referred to you because of prolonged bleeding following circumcision. You also note some bleeding of the gums. Coagulation tests reveal a normal PT but a raised APTT and an increased Bleeding Time. Analysis of clotting factors reveals a low Factor VIII.

Answer 890

vWD

Question 891

A 9 month old boy presents to A&E with excessive bleeding following circumcision. Laboratory investigations reveal a prolonged activated partial thromblastin time (APTT), normal prothrombin time (PT) and a factor VIII level which is 10% of normal. Bleeding time is normal. What is the likely diagnosis?

Answer 891

Haemophilia A

Question 892

A 65-year-old man is referred to the haematology department by his GP after initially presenting with tiredness, palpitations, petechiae and recent pneumonia. His blood tests reveal Hb 9.8 (13–18 g/dL), MCV 128 (76–96 fL), reticulocyte count 18 (25–100 × 109/L), 1.2 (2–7.5 × 109/L) and platelet count 125 (150–400 × 109/L). B β-Thalassaemia C Anaemia of chronic disease D Blood loss E Alcohol F Vitamin B12 deficiency G Renal failure H Aplastic anaemia I Lead poisoning

Answer 892

Aplastic anaemia (H) is caused by failure of the bone marrow resulting in a pancytopenia and hypocellular bone marrow. Eighty per cent of cases are idiopathic, although 10 per cent are primary (dyskeratosis congenita and Fanconi anaemia) and 10 per cent are secondary (viruses, SLE, drugs and radiation). The pathological process involves CD8+/ HLA-DR+ T cell destruction of bone marrow resulting in fatty changes. Investigations will reveal reduced Hb, reticulocytes, neutrophils, platelets and bone marrow cellularity as well as a raised MCV. Macrocytosis results from the release of fetal haemoglobin in an attempt to compensate for reduced red cell production.

Question 893

Microcytic hypochromic anaemia Rouleaux formation Raised ferritin Reduced serum Fe and TIBC

Answer 893

ACD

Question 894

Normocytic anaemia

Answer 894

Blood loss can cause this due to the reduced number of circulating RBCs

Question 895

Basphillic stippling Microcytic anaemia

Answer 895

Suggestive of Pb poisoning

Question 896

Causes of warm type AIHA

Answer 896

IgG mediated and occurs at 37 deg Lymphoproliferative diseases Autoimmune diseases

Question 897

Causes of cold type AIHA

Answer 897

IgM mediated and occurs at less than 4 Mycoplasma or EBV infection

Question 898

Rare stem cell disorder resulting in intravascular haemolysis, Hburia and thrombophilia

Answer 898

PNH

Question 899

Causes of anisocytosis

Answer 899

IDA most common Thalassaemia Megaloblastic anaemia Sideroblastic anaemia all causative too

Question 900

Dacrocytes

Answer 900

Tear drop cells caused by myelofibrosis

Question 901

Blood film will demonstrate leuko-erythroblasts, tear-drop cells and circulating megakaryocytes.

Answer 901

Myelofibrosis Occurs due to extra-medullary haematopoeisis Remember dry tap on BM aspirate with splenomegaly

Question 902

Causes of Heinz bodies

Answer 902

Most commonly caused by erythrocyte enzyme deficiencies i.e. G6PDD NADPHD Chronic liver disease and alpha thalassaemia

Question 903

Rouleaux formation

Answer 903

Occurs in high plasma protein states e.g. MM

Question 904

Target cells

Answer 904

Erythrocytes with a central area of staining, ring of pallor and an outer ring of staining. Formed in thalassaemia, asplenia and liver disease

Question 905

Pappenheimer bodies

Answer 905

Granules of iron found within erythrocytes Pb poisoning Sideroblastic anaemia Haemolytic anaemia

Question 906

A Immune thrombocytopenic purpura B Idiopathic thrombotic thrombocytopenic purpura C Disseminated intravascular coagulation D Glanzmann’s thrombasthenia E Von Willebrand disease F Haemophilia A G Haemophilia B H Hereditary haemorrhagic telangiectasia I Bernard–Soulier syndrome A 4-year-old girl is seen by her GP due to recent onset petechiae on her feet and bleeding of her gums when she brushes her teeth. The child’s platelet count is found to be 12 500 per μL. The GP prescribes prednisolone and reassures the child’s mother that the bleeding will resolve.

Answer 906

Immune thrombocytopenic purpura (ITP; A) may follow either an acute or chronic disease process. Acute ITP most commonly occurs in children, usually occurring 2 weeks after a viral illness. It is a type 2 hypersensitivity reaction, with IgG binding to virus-coated platelets. The fall in platelets is very low (less than 20 × 109/L) but is a self-limiting condition (few weeks). Chronic ITP is gradual in onset with no history of previous viral infection. It is also a type 2 hypersensitivity reaction with IgG targeting GLP-2b/3a.

Question 907

Pentad in TTP

Answer 907

MAHA Renal failure Thrombocytopenia Fever Neurological signs

Question 908

Pathophysiology of TTP

Answer 908

Mutation in ADAM-ST13 gene coding for a protease that cleaves vWD allows for the formation of vWF multimers enabling platelet thrombi to form, causing organ damage TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in the small blood vessels. Platelets are consumed in the aggregation process, and bind vWF. These platelet-vWF complexes form small blood clots which circulate in the blood vessels and cause shearing of red blood cells, resulting in their rupture.[3] Roughly, the two forms of TTP are idiopathic and secondary TTP. A special case is the inherited deficiency of ADAMTS13, known as the Upshaw-Schülman syndrome

Question 909

Investigations will reveal a high/ normal APTT, low factor 8 levels, low ristocetin cofactor activity, poor ristocetin aggregation and normal PTT,

Answer 909

vWD

Question 910

A Factor V Leiden B Antiphospholipid syndrome C Malignancy D Protein S deficiency E Antithrombin deficiency F Prothrombin G20210A mutation G Oral contraceptive pill H Buerger’s disease I Chronic liver disease 1 A 35-year-old Caucasian man presents to accident and emergency with deep pain and swelling in his left calf. His past medical history reveals history of recurrent DVTs. The patient’s notes reveal a letter from his haematologist who had diagnosed a condition caused by a substitution mutation.

Answer 910

Prothrombin G20210A (F) is an inherited thrombophilia caused by the substitution of guanine with adenine at the 20210 position of the prothrombin gene. Physiologically, prothrombin promotes clotting after a blood vessel has been damaged. The G20210A causes the amplification of prothrombin production thereby increasing the risk of clotting, and causing a predisposition to deep vein thrombosis and pulmonary embolism. The prevalence of the mutation is approximately 5 per cent in the Caucasian population, the race with the greatest preponderance.

Question 911

5 A 37-year-old man presents to accident and emergency with shortness of breath and severe pleuritic chest pain. A CTPA reveals the diagnosis of pulmonary embolism. The patient’s haematological records state the patient has a condition that leads to the persistence of factors 5a and 8a causing increased risk of venous thrombosis.

Answer 911

Protein S deficiency (D) is associated with the impaired degradation of factors Va and VIIIa. Protein S and protein C are physiological anticoagulants. Deficiency of protein S leads to persistence of factors 5a and 8a in the circulation and hence patients have a susceptibility to venous thrombosis. Three types of protein S deficiency exist: type I (quantitative defect) and types II and III (qualitative defect). Since protein S is a vitamin K dependent anticoagulant, warfarin treatment and liver disease may also lead to venous thrombosis in rare cases (the majority of cases show increased bleeding).

Question 912

Why does pancreatic cancer predispose to thrombosis

Answer 912

Because tumour cells express tissue factor

Question 913

4 A 56-year-old man is given a blood transfusion following severe blood loss after a hip replacement operation. Three hours after the transfusion, the patient develops shortness of breath, a dry cough and a fever of 39°C. A Immediate haemolytic transfusion reaction B Febrile non-haemolytic reaction C Iron overload D IgA deficiency E Transfusion related lung injury F Bacterial infection G Delayed haemolytic transfusion reaction H Fluid overload I Graft versus host disease

Answer 913

Transfusion-related lung injury (TRALI; E) is characterized by acute non-cardiogenic pulmonary oedema that occurs within 6 hours following blood transfusion. The pathogenesis of TRALI involves the presence of anti-white blood cell antibodies in the donor blood that attack host leukocytes; sensitizing events in donors include previous blood transfusion or transplantation. Clinical features of TRALI are dry cough, dyspnoea and fever.

Question 914

Which ABO incompatibility causes the most severe IHTR

Answer 914

Group O patient infused with group A blood

Question 915

What is delayed TR also known as

Answer 915

Non-ABo reacition

Question 916

A Acute lymphoblastic leukaemia B Acute promyelocytic leukaemia C Chronic myeloid leukaemia D Chronic lymphocytic leukaemia E Hairy cell leukaemia F T-cell prolymphocytic leukaemia G Large granular lymphocytic leukaemia H Adult T-cell leukaemia I Acute myeloid leukaemia 2 A 41-year-old man is referred to a haematologist by his general practitioner after several recent chest infections and tiredness. On examination, bruises are seen on his lower limbs as well as splenomegaly. Initial blood tests reveal a pancytopenia. Further testing demonstrates the presence of tumour cells that express tartrate-resistant acid phosphatase

Answer 916

Hairy cell leukaemia (HCL; E) is a haematological malignancy of B lymphocytes and a subtype of chronic lymphocytic leukaemia. It most commonly occurs in middle-aged men. The cancer derives its name from the fine hair-like projections that are seen on tumour cells on microscopy. Cell surface markers include CD25 (IL-2 receptor) and CD11c (adhesion molecule). Diagnosis can be confirmed by the presence of tartrate-resistant acid phosphatase (TRAP) on cytochemical analysis. Clinical features relate to invasion of the spleen (splenomegaly), liver (hepatomegaly) and bone marrow (pancytopenia).

Question 917

Characteristic clover leaf appearance of nuclei

Answer 917

Adult T cell leukaemia

Question 918

caused by a translocation mutation forming PML-RAR leading to proliferation of promyelocytes.

Answer 918

Acute promyelocytic leukaemia (APML; B) is the M3 subtype of acute myeloid leukaemia

Question 919

The most common causative mutation is an inversion in chromosome 14: inv 14(q11;q32).

Answer 919

T-cell prolymphocytic leukaemia (T-PLL; F) is an aggressive T-cell leukaemia

Question 920

characterized by the presence of large lymphocytes in the blood stream and bone marrow that contain azurophilic granules.

Answer 920

Large granular lymphocytic leukaemia

Question 921

binucleate/multinucleate cells with abundant cytoplasm, inclusion-like nucleoli and surrounded by eosinophils

Answer 921

Reed–Sternberg cells

Question 922

A 60-year-old man presents to his GP with malaise, night sweats and weight loss. On examination the patient is found to have generalized lymphadenopathy and hepatomegaly. Cytogenetic investigation a few weeks later by a haematologist reveals a translocation between chromosomes 11 and 14, which has caused overexpression of the BCL-2 protein A Diffuse large B-cell lymphoma B Burkitt lymphoma C Follicular lymphoma D Small lymphocytic leukaemia E Mantle cell lymphoma F Peripheral T-cell lymphoma G Mycosis fungoides H Angiocentric lymphoma I Hodgkin’s lymphoma

Answer 922

Mantle cell lymphoma (MCL; E) is an aggressive B-cell lymphoma primarily affecting elderly men. The most common cause is a translocation between chromosomes 11 and 14, involving the BCL-1 locus and Ig heavy chain locus, therefore leading to over-expression of cyclin D1. Over-expression of cyclin D1 leads to dysregulation of the cell cycle. Clinically, generalized lymphadenopathy, as well as bone marrow and liver infiltration, are common. Hodgkin’s lymphoma can be split into classical and lymphocyte predominant nodular (LPN) subtypes.

Question 923

A Diffuse large B-cell lymphoma B Burkitt lymphoma C Follicular lymphoma D Small lymphocytic leukaemia E Mantle cell lymphoma F Peripheral T-cell lymphoma G Mycosis fungoides H Angiocentric lymphoma I Hodgkin’s lymphoma A 40-year-old woman is referred to a haematologist after she is found to have generalized, painless lymphadenopathy. A report on tumour cell morphology states the presence of both centrocytes and centroblasts.

Answer 923

Follicular lymphoma (C) is caused most commonly by a translocation between chromosomes 14 and 18, leading to over-expression of the BCL-2 protein. Over-expression of BCL-2 causes inhibition of apoptosis, promoting the survival of tumour cells. Tumour cells in follicular lymphoma are characterized by centrocytes (small B cells with irregular nuclei and reduced cytoplasm) and centroblasts (larger B cells with multiple nuclei). Clinical features include painless, generalized lymphadenopathy. Follicular lymphoma usually presents in middle-aged patients and has a non-aggressive course but is difficult to cure.

Question 924

A Diffuse large B-cell lymphoma B Burkitt lymphoma C Follicular lymphoma D Small lymphocytic leukaemia E Mantle cell lymphoma F Peripheral T-cell lymphoma G Mycosis fungoides H Angiocentric lymphoma I Hodgkin’s lymphoma 62-year-old HIV-positive man presents to a haematologist with a 3-month history of weight loss and tiredness. On examination, the patient has a mass on his neck which the patient states has been rapidly growing. Staining of biopsy tissue demonstrates the present of large B cells which are positive for EBV.

Answer 924

Diffuse large B-cell lymphoma (DLBL; A) is a haematological malignancy most commonly affecting the elderly, characterized by large lymphocytes which have a diffuse pattern of growth. Common chromosomal abnormalities which contribute to the development of DLBL include the t(14;18) translocation which is characteristic of follicular lymphoma; this suggests that follicular lymphoma may undergo a degree of transformation to cause DLBL in such circumstances. Tumour cells that have follicular lymphoma morphology may be present at other sites. Two subtypes of DLBL have been described, both of which are associated with immunodeficiency: immunodeficiency- associated large B-cell lymphoma (linked to latent EBV infection) and body cavity-based large cell lymphoma (linked to HHV8 infection).

Question 925

indistinguishable from chronic lymphocytic leukaemia (CLL) in terms of genetics and morphology but more commonly presents with greater peripheral blood lymphocytosis than CLL.

Answer 925

Small lymphocytic lymphoma

Question 926

presents in adulthood as cutaneous masses most commonly in the nasal area. Tumour cells will express NK-cell markers and commonly may be infected with EBV.

Answer 926

Angiocentric lymphoma

Question 927

A 72-year-old man presents with a 1-month history of fever, night sweats and weight loss. Blood tests reveal a monocyte count of 1400/mm3 in the peripheral blood and a bone marrow biopsy demonstrates that myeloblasts constitute 16 per cent of his bone marrow. A Essential thrombocythaemia B Myelofibrosis C Chronic myelo-monocytic leukaemia D Refractory anaemia with excess blasts E Polycythaemia rubravera F Refractory anaemia with ringed sideroblasts G Refractory anaemia H 5q-Syndrome I Multiple myeloma

Answer 927

Chronic myelo-monocytic leukaemia (CMML; C) is a myelodysplastic/ myeloproliferative disease which most commonly affects the elderly population, defined by a monocytosis of \>1000/mm3 and increased number of monocytes in the bone marrow. Myeloblasts make up \<5 per cent of the peripheral blood and \<20 per cent of the bone marrow. Eosinophilia may be present in CMML associated with a t(5;12) translocation. The Philadelphia chromosome BCR/ABL fusion gene is not responsible for causing CMML. Commonly, patients will present with fever, fatigue, night sweats; on examination hepatomegaly and/or more commonly splenomegaly may be present.

Question 928

Features include hypo-lobulated megakaryocytes and an increased/ normal platelet count.

Answer 928

5q-Syndrome (H) is caused by deletion of the long arm of chromosome 5.

Question 929

is defined by fewer than 5 per cent myeloblasts present in the bone marrow.

Answer 929

Refractory anaemia

Question 930

is a myelodysplastic disease characterized by fewer than 5 per cent myeloblasts in the bone marrow, but greater than 15 per cent erythrocyte precursors stuffed with iron in their mitochondria.

Answer 930

Refractory anaemia with ringed sideroblasts

Question 931

Refractory anaemia with excess blasts (D)

Answer 931

is a myelodysplastic disease that may be classified into type 1 (5–9 per cent myeloblasts in the bone marrow) or type 2 (10–19 per cent myeloblasts in the bone marrow).

Question 932

Pathophysiology in ACD

Answer 932

Il-6 produced by macrophages induced hepcidin production by the liver which has the effect of retaining Fe in macrophages and decreases export from enterocytes (thus reducing plasma iron levels)

Question 933

What conditions can cause a monocytosis

Answer 933

Sarcoidosis Brucellosis, typohid, VZV CMML

Question 934

Features of FHTR

Answer 934

Febrile haemolytic transfusion reactions (A) typically occur less than 24 hours after the transfusion. These reactions are thought to be due to antibodies in the patient reacting with white cell antigens in the donor blood, or due to cytokines which build up in the blood products during storage. These reactions usually only warrant slowing the transfusion, and giving an anti-pyretic if needed.

Question 935

Pencil cells

Answer 935

Type of elliptocyte that occur in IDA, thalassaemia and PK deficiency

Question 936

Howell-Jolly bodies Target cells Occasional nucleated RBCs Lymphocytosis Macrocytosis Acanthocytes

Answer 936

Hyposeplnism

Question 937

Target cells the 3 Hs

Answer 937

Hepatic pathology Hyposplenism Hbopathies

Question 938

spiculated red cells that are found in hyposplenism, α-β-lipoproteinaemia, chronic liver disease and α-thalassaemia trait

Answer 938

Acanthocytes

Question 939

The PIIES

Answer 939

Haematological diseases in which splenectomy may be of benefit Thalassaemias Pyrukvate kinase Immune haemolytic anaemia Idiopathic thyrombocytopenic purpura Elliptocytosis Spherocytosis (hereditary)

Question 940

HbA

Answer 940

a2 b2

Question 941

HbA2

Answer 941

a2 d2

Question 942

HbF

Answer 942

a2 g2

Question 943

HbC

Answer 943

these patients may have a mild splenomegaly and haemolytic anaemia. Haemoglobin C is similar to haemoglobin S in that it comprises two normal alpha chains and two variant beta chains in which lysine has replaced glutamic acid at position 6.

Question 944

Pathogenesis of aplastic crises in parvovirus infection and SCD

Answer 944

The virus affects erythropoiesis by invading erythrocyte precursors and destroying them. Infants and children with sickle cell disease initially have no immunity to parvovirus B19, and their first exposure can lead to pure red cell aplasia. In a normal individual the virus blocks red cell production for 2 or 3 days with little consequence, but it can be life threatening in sickle cell patients in whom the red cell life span is already shortened. This can lead to profound anaemia over the course of just a few days, and a dramatic drop in the reticulocyte count. Serum IgM antibodies to parvovirus B19 can confirm the diagnosis, and blood transfusion may be required.

Question 945

A 26-year-old pregnant woman is found to have an Hb of 9.5 g/dL on a routine blood test, with an MCV of 70. Serum electrophoresis reveals an Hb A2 of 3.9 per cent and Hb A of 96.1 per cent. Her ferritin levels are normal. The most likely diagnosis is: A Iron deficiency anaemia B Cooley’s anaemia C b-Thalassaemia intermedia D b-Thalassaemia minor E a-Thalassaemia

Answer 945

b-Thalassaemias are a group of genetic haemoglobinopathies that essentially result in reduced or absent formation of the beta chains of haemoglobin leading to anaemia of varying degrees of severity. They are prevalent in the Middle East, Central, South and South East Asia, Southern China and around the Mediterranean. There are three main forms: thalassaemia major, thalassaemia intermedia and thalassaemia minor. In b-thalassaemia minor (D) only one of the b-globulin alleles is mutated, so these individuals usually only have a well-tolerated microcytic anaemia (Hb \>9 g/dL) which is clinically asymptomatic. They might be picked up on a routine blood test, with a low MCH and significantly low MCV (\<80 fL). They also have an increase in the fraction of Hb A2, as in this case. In most people the fraction of Hb A2 (α2δ2) will be 1.5–3.5 per cent, but in b-thalassaemia minor the proportion of Hb A2 is \>3.5–4 per cent to compensate for the reduced amount of normal haemoglobin, and they might have a slight increase in Hb F. It can worsen in pregnancy, as in this case

Question 946

Cooley's anaemia=

Answer 946

Beta thalassaemia major

Question 947

Cold LID

Answer 947

Cold AIHA Lymphoproliferative disease e.g. CLL, lymphomas Infections: mycoplasma, EVC Don't know i.e. idiopathic

Question 948

Treatment of cold AIHA

Answer 948

Avoiding cold conditions Chlorambucil Treat underlying cause

Question 949

Treatment of warm AIHA

Answer 949

Steroids Ig Splenectomy

Question 950

Presentation of PNH

Answer 950

Pancytopenia New thrombus HA Paroxysmal nocturnal haemoglobinuria (B) is another rare acquired disease, but one that is potentially life threatening. The resulting defect in the red cell membrane leads to intravascular haemolysis. The disease has three aspects: the most common way for it to present is with a haemolytic anaemia, which may cause haemoglobinuria, especially overnight. The second aspect is thrombophilia, which can present with visceral thrombosis (e.g. CNS, pulmonary, mesenteric). The third aspect is deficient haematopoiesis which can cause a pancytopenia with aplastic anaemia.

Question 951

A 34-year-old woman with known Addison’s disease is brought to the GP by her husband, as he is concerned that she keeps falling over at night. On examination the GP notes that she has conjunctival pallor. A thorough neurological examination reveals absent knee jerks, absent ankle jerks and extensor plantars bilaterally. Which of the following is the most sensitive test for the condition she has developed? A Anti-intrinsic factor antibodies B Anti-endomysial cell antibodies C Anti-smooth muscle antibodies D Anti-parietal cell antibodies E Anti-voltage gated calcium channel antibodies

Answer 951

Intrinsic factor antibodies (A) can be found in approximately 50 per cent of patients, and are specific for pernicious anaemia but not as sensitive as anti-parietal cell antibodies (D) which are found in \>90 per cent of patients. This woman has developed pernicious anaemia leading to vitamin B12 deficiency. It can be associated with other autoimmune conditions, such as Addison’s disease or thyroid disease. Specifically, she has developed a condition called subacute combined degeneration of the cord (SACD) which has led to symmetrical loss of dorsal columns (resulting in loss of touch and proprioception leading to ataxia, and LMN signs) and corticospinal tract loss (leading to UMN signs), with sparing of pain and temperature sensation (which is carried by spinothalamic tracts). The ataxia and loss of joint position sense have resulted in her falling at night, which may be exacerbated by optic atrophy – another manifestation of vitamin B12 deficiency. Remember that vitamin B12 is found in meat, fish and dairy products. More common causes of vitamin B12 deficiency can be related to diet (e.g. vegans) or to malabsorption. It is absorbed in the terminal ileum after binding to intrinsic factor produced by the parietal cells in the stomach. Causes of malabsorption can therefore be related to the stomach (e.g. post gastrectomy, pernicious anaemia), or due to the terminal ileum (e.g. Crohn’s, resection of the terminal ileum, bacterial overgrowth). Pernicious anaemia is caused by an autoimmune atrophic gastritis when autoantibodies are produced against parietal cells and intrinsic factor itself. The lack of B12 impairs DNA synthesis in red blood cells, leading to the production of large, megaloblastic erythrocytes.

Question 952

* Low haemoglobin * High MCV * Low platelets and WCC if severe * Hypersegmented neutrophils * Megaloblasts in the bone marrow * Cabot rings in RBCs

Answer 952

B12 deficiency

Question 953

Causes of macrocytosis

Answer 953

1. Megaloblastic: folate and B12 deef 2. Non-megaloblastic RALPH 2. Other haematological disorders e.g. myelodysplasia, aplastic anaemia, myeloma, myeloproliferative disorders

Question 954

RALPH

Answer 954

Non-megaloblastic causes of macrocytic anaemia Reticulocytosis Alcohol Liver disease Pregnancy Hypothyroidism

Question 955

Drugs causing aplastic anaemia

Answer 955

All the Cs Cytotoxics Carbamezepine Chloramphenicol Anticonvulsants- phenytoin

Question 956

A 50-year-old diabetic man sees his GP complaining of generalized tiredness and a painful right knee. He is found on examination to have five finger breadths of hepatomegaly. An X-ray of his right knee is reported as showing chondrocalcinosis. His blood tests are likely to reveal: A Raised MCV B Raised total iron binding capacity C Reduced serum ferritin D Reduced iron level E Raised transferrin saturation

Answer 956

This man has hereditary haemachromatosis, an inherited disorder of iron metabolism. It is particularly common in those of Celtic descent, and the gene responsible for the majority of cases is the HFE gene on chromosome 6. Increased iron absorption leads to deposition to multiple organs including: • the liver (hepatomegaly, deranged LFTs) • joints (arthralgia, chondrocalcinosis) • pancreas (diabetes) • heart (dilated cardiomyopathy) • pituitary gland (hypogonadism and impotence) • adrenals (adrenal insufficiency) • skin (slate grey skin pigmentation) Blood tests can show deranged LFTs as in this case, as well as a raised serum ferritin, raised serum iron, reduced or normal total iron binding capacity and raised transferrin saturation (E) (\>80 per cent).

Question 957

Low Fe High TIBC/transferrin Low transferrin saturation Low ferritin

Answer 957

IDA

Question 958

High Fe Low or normal TIBC/transferrin Low Transferrin saturation High ferritin

Answer 958

Haemochormatosis

Question 959

Low Fe Low TIBC/Transferrin Low transferrin saturation High ferritin

Answer 959

ACD

Question 960

High iron Low TIBC/transferrin High transferrin saturation High ferritin

Answer 960

Chronic haemolysis

Question 961

A 67-year-old woman presented with polyuria and polydipsia on a background of ongoing bone pain. Her blood tests revealed a high calcium, and a serum electrophoresis was sent. Her serum paraprotein was 25 g/L and a bone marrow biopsy revealed 6 per cent clonal plasma cells. The most likely diagnosis is: A Plasma cell dyscrasia B Monoclonal gammopathy of undetermined significance C Smouldering myeloma D Multiple myeloma E Hypercalcaemia with no evidence of underlying malignancy

Answer 961

Symptomatic myeloma (D):

Question 962

Clonal plasma cells on bone marrow biopsy • Paraprotein in either serum or urine • Evidence of end-organ damage attributed to the plasma cell disorder, commonly remembered using the acronym ‘CRAB’ (Calcium – high, Renal insufficiency, Anaemia and Bone lesions)

Answer 962

Symptomatic myeloma (D):

Question 963

* Serum paraprotein \>30 g/L AND/OR * Clonal plasma cells \>10 per cent on bone marrow biopsy AND * NO myeloma-related organ or tissue impairment

Answer 963

Asymptomatic (smouldering) myeloma (C):

Question 964

* Serum paraprotein \<30 g/L AND * Clonal plasma cells \<10 per cent on bone marrow biopsy AND * NO myeloma-related organ or tissue impairment

Answer 964

Monoclonal gammopathy of undetermined significance (MGUS)

Question 965

A 39-year-old motorcyclist is admitted following a road traffic accident complicated by severe burns. Several days later he is due to go home, when oozing is noted from his cannula site and he has several nose bleeds. Repeat blood tests reveal an Hb of 12.2 g/dL, WCC of 11.2 × 109/L, and platelets of 28 × 109/L. A coagulation screen shows a prolonged APTT and PT. He also has a reduced fibrinogen and raised D-dimers. The most likely diagnosis is: A Liver failure B Disseminated intravascular coagulation C Thrombotic thrombocytopenic purpura D Aplastic anaemia E Heparin induced thrombocytopenia

Answer 965

This man has developed disseminated intravascular coagulation (DIC) (B) following his severe burns. DIC is widespread pathological activation of the clotting cascade in response to various insults. The cascade is activated in various ways: one mechanism is the release of a transmembrane glycoprotein called ‘tissue factor’ in response to cytokines or vascular damage. This results in fibrin formation, which can eventually cause occlusion of small and medium sized vessels and lead to organ failure. At the same time, depletion of platelets and coagulation proteins can result in bleeding (as in this case).

Question 966

Causes of DIC I'M STONeD

Answer 966

Immunological e.g. severe allergic reactions Miscellaneous e.g. aortic aneurysm, liver disease Sepsis Trauma Obstetric e.g. amniotic fluid embolism, placental abruption Neoplastic Drugs and toxins

Question 967

Blood tests will typically reveal a thrombocytopenia, raised PT and APTT, decreased fibrinogen and increased D dimers.

Answer 967

DIC

Question 968

MARCH with low plt

Answer 968

TTP MAHA A fever Renal failure Fluctuating CNS signs Haematuria/proteinuria Low platelet count

Question 969

caused by the spirochaete Leptospira interrogans, and is spread by infected rat urine. Although it can cause an abrupt onset of renal failure and a fever, it would not typically result in thrombocytopenia or features of MAHA.

Answer 969

Weil's disease

Question 970

Answer 970

Question 971

Answer 971

Question 972

Answer 972

Question 973

Answer 973

Question 974

Answer 974

Question 975

Answer 975

Question 976

Answer 976

Question 977

A 56-year-old woman with known cirrhosis presents with falls. On examination she is clinically jaundiced and rectal examination reveals malaena. Blood tests reveal an INR of 2.2. She is diagnosed with decompensated chronic liver disease. Which of the following is not a vitamin K dependent clotting factor? A Thrombin B Factor VII C Factor VIII D Protein C E Factor X

Answer 977

C

Question 978

What are the vitamin K dependant clotting factors?

Answer 978

II VII IX X Protein C S and Z

Question 979

How does Warfarin influence clotting facotr production

Answer 979

Still produced but they lack efficacy due to an inability to interact with calcium or platelet facotr 3

Question 980

What are the phases of the exrinsic pathway

Answer 980

Initiation phase: Factor VIIa activates downstream factors Ix and X Amplification phase: Xa/Va activates prothrombin to thrombin which then activates XI, VIII and V resulting in the prothrombinase complex This explodes with thrombin generating activity to produce fibrin rapidly and stabilise the platelet clot= propagation phase

Question 981

Patients with chronic abdominal pain, weight loss, raised ESR with a known abdominal aneurysm should prompt the thought of

Answer 981

an inflammatory aneurysm subtype. In these patients the inflammatory process sometimes encases the nearby ureters causing obstruction and eventually hydronephrosis.

Question 982

A 62-year-old man presents with shortness of breath. This has been gradually getting worse for the last few years and is associated with chronic productive cough. He is a heavy smoker. His chest X-ray reveals a hyperexpanded chest with no other abnormalities. His bloods tests are normal except for a raised haemoglobin and raised haematocrit. What is the most likely cause for this? A Polycythaemia rubra vera B Idiopathic erythrocytosis C Secondary polycythaemia D Gaisbock’s disease E Combined polycythaemia

Answer 982

Combined polycythaemia (E), also known as smoker’s polycythaemia, has multiple aetiological factors. Cigarettes contain high concentrations of carbon monoxide gas which bind avidly to haemoglobin, thus displacing oxygen. This leads to increased erythropoietin (EPO) secretion from the hypoxic renal interstitium. EPO promotes erythrocyteproliferation and differentiation and prevents their apoptosis in the bone marrow, thus increasing red cell mass. Smoking is also a significant risk factor for chronic obstructive pulmonary disease, which is what this man suffers from. The obstructed airways reduce oxygen delivery to the alveoli and pulmonary vessels they supply thus causing a reduction of oxygen supply furthering the hypoxia. Finally, smokers also have an associated reduced plasma volume, thus increasing the relative concentration of haemoglobin. This is therefore ‘combined’ because of the presence of both increased red cell mass and reduced plasma volume.

Question 983

Gaisbock’s disease

Answer 983

``` Haemoglobin may be raised with relative deficiency of plasma (i.e. relative or apparent polycythaemia, historically known as Gaisbock’s disease (D)). ```

Question 984

the label given to those with polycythaemia secondary to JAK2 mutation, but not with the V617F exon 14 mutation, e.g. exon 12 mutations.

Answer 984

Idiopathic erythrocytosis (B)

Question 985

What is important to note re a positive diptick for blood?

Answer 985

May represent Hburia or myoglobinuria

Question 986

an acquired clonal stem cell disorder characterized by an abnormal erythrocyte sensitivity to the lytic complement pathway. There is a deficiency of glucosyl phosphatidyl inositol (GPI) linked proteins namely CD55 (decay-accelerating factor) and CD59 (membrane inhibitor or reactive lysis).

Answer 986

Paroxysmal nocturnal haemoglobinuria

Question 987

Causes of MAHA

Answer 987

Mechanical destruction of RBCs E.g. Heart valve DIC TTP HUS

Question 988

What differentiates between apparent and true polycythaemia

Answer 988

Red cell count is measured as the number of erythrocytes in a quantum of plasma, whereas red cell mass is determined by isotope studies quoted as mL/kg. It is a measure of absolute red cell mass and is therefore not affected if someone is dehydrated, for example, where the relative plasma volume is reduced giving a falsely high red cell concentration. There are many situations where the red cell concentration and red cell mass do not parallel each other, e.g. vomiting, diarrhoea or overuse of diuretics. If a patient has increased red cell concentration this may therefore be absolute or relative – the latter being secondary to reduced plasma volume thus making the polycythaemia secondary to haemoconcentration. Absolute polycythaemia may be primary or secondary.

Question 989

von Willebrand’s disease is characterized by abnormal platelet aggregation when they are exposed to: A Streptomycin B Aspirin C Fibrinogen D Collagen E Ristocetin

Answer 989

``` von Willebrand’s disease (vWD) is characterized by a quantitive or qualititative defect in von Willebrand factor (vWF). Ristocetin, an antibiotic no longer used clinically, causes vWF to bind the platelet receptor glycoprotein Ib (GlpIb) through an unknown mechanism. If ristocetin is added to platelets with defective vWF or defective GlpIb (called Bernard–Soulier syndrome) then platelet aggregation does not occur. It will occur, however, with other pro-aggregative factors including collagen (D) and fibrinogen (C). If vWF or GlpIb is absent, aggregation does not occur with collagen as there is no molecular link between collagen and the platelet. However, this is the case with all patients with vWF. ```

Question 990

Inherited platelet defects

Answer 990

Glanzmann’s thrombasthenia (an inherited lack of GlpIIb/IIIa) where fibrinogen cannot cross-link platelets during the initial platelet aggregative stage of thrombosis. Understanding these receptors and their importance in platelet aggregation has led to the development of powerful antiplatelet medications including adciximab, eptifibatide and tirofiban. Other inherited platelet diseases include storage pool diseases, e.g. grey platelet syndrome, Quebec platelet disorder, Hermansky–Pudlak syndrome and Chediak–Higashi syndrome. These refer to defects of the alpha and dense granules in the platelet which are released to promote platelet aggregation.

Question 991

What is the mechanism through which DS may increase the chance of AML

Answer 991

Dosage affect due to chromosome 21 duplication

Question 992

associated with translocation and dysregulation of the c-myc gene on chromosome 8 including t(8;14), t(2;8) and t(8;22).

Answer 992

Burkitt’s lymphoma

Question 993

Histologically, a nodular growth pattern with a mixture of centrocytes and centroblasts is characteristic. The proportion of centroblasts found determines the tumour grade which has therapeutic implications. These cells are CD10 and BCL-6 positive in the majority. It is usually indolent but can transform into a high grade lymphoma

Answer 993

Follicular lymphoma

Question 994

arises mainly at extranodal sites due to chronic antigenic stimulation and malignant transformation. It is a B-cell NHL arising from marginal cells in the lymph node. There are clinically three subtypes: extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT); nodal marginal zone B-cell lymphoma; and splenic marginal zone B-cell lymphoma

Answer 994

Marginal zone lymphoma

Question 995

usually affects elderly men presenting with lymphadenopathy and constitutional ‘B’ symptoms (weight loss, fever, drenching night sweats) in one-third. It is the most common histological subtype of NHL. The diagnosis is usually made with an excisional biopsy demonstrating pan-B cell markers, e.g. CD20, and CD79a. Histologically, there is effacement of normal architecture by sheets of atypical lymphoid cells. The cell of origin is the centrob

Answer 995

DLBL

Question 996

It typically affects middleaged men with lymphadenopathy and gastrointestinal tract involvement including spleen and Waldeyer’s ring. It usually presents with advanced disease and involves any region of the GI tract occasionally presenting as multiple intestinal polyps. Nuclear staining for cyclin D1 is present in 95 per cent of cases and is strongly associated with the t(11;14) (q13;q32) mutation – a translocation between cyclin D1 locus and immunoglobulin heavy chain locus. This

Answer 996

Mantle cell lymphoma

Question 997

This cell is known as the lymphocytic and histiocytic cell or L&H variant. Sometimes these cells are referred to as ‘popcorn’ cells because their nucleus resembles an exploded popcorn kernel. This subtype of HL accounts for 5 per cent of cases and has a bimodal age distribution – children and adults between the ages of 30 and 40.

Answer 997

Nodular lymphocytic HL | (Non-classical)

Question 998

is characterized by at least a partially nodular grown pattern, with fibrous bands separating nodules.

Answer 998

Nodular sclerosing classical HL

Question 999

heterogeneous group with a diffuse or vaguely nodular growth patter without band-forming sclerosis.

Answer 999

Mixed cellularity HL

Question 1000

most commonly has a nodular growth pattern. In this subtype, cells resembling L&H variants may be present making the distinction from non-classical lymphoma more difficult. The background infiltrate consists predominantly of lymphocytes, with rare eosinophils or neutrophils.

Answer 1000

Lymphocyte rich HL

Question 1001

subtype has a diffuse growth pattern and appears hypocellular with a lack of inflammatory cells. This subtype has a poor prognosis.

Answer 1001

HL lymhpocyte depleted

Question 1002

Why can women be affected in G6PD?

Answer 1002

Unlike some other X-linked conditions, women can be affected due to the random nature of X chromosome inactivation (lyonization) which leads to some cells being vulnerable to oxidative stress.

Question 1003

Haptoglobin in intravascular and extravascular haemolysis

Answer 1003

Haptoglobin circulates in the plasma and avidly binds to free haemoglobin to be later removed by the reticuloendothelial system. It is therefore reduced in intravascular haemolysis only. Extravascular haemolysis occurs mainly in the spleen where free haemoglobin is not released into the circulation and therefore haptoglobin levels are generally unchanged.

Question 1004

A 35-year-old Asian woman presents with tiredness. The full blood count shows: Haemoglobin: 10.1 g/dL (11.5–16.5) Platelet count: 160 × 109 (150–400 × 109) White cell count: 6.6 × 109 (4–11 × 109) Mean cell volume: 62 fL (80–96 fL) Hb A2: 6.3 per cent (2–3 per cent) Which of the following is the most likely diagnosis? A Sickle cell disease B Acute myeloid leukaemia C b-Thalassaemia major D b-Thalassaemia trait E Hereditary spherocytosis

Answer 1004

This woman presents with microcytic anaemia, the most common cause of which is iron deficiency. However, the mean cell volume is disproportionally reduced compared with the degree of anaemia indicating there might be a haemoglobinopathy present. The presence of increased Hb A2 confirms the diagnosis of b-thalassaemia trait.

Question 1005

raised RDW with increased MCHC is very suggestive of this condition.

Answer 1005

Hereditary psherocytosis

Question 1006

A 62-year-old man presents with bruising and tiredness. Examination reveals moderate splenomegly and his a reveal a normocytic anaemia with blood tests platelet count of 900 × 109/L, neutrophilia, basophilia, numerous myelocytes and 4 per cent myeloblasts. The neutrophils have low leukocyte alkaline phosphatase levels. Which of the following is likely to be present in this patient? A t(9;22) B t (8;14) C BCR-Abl fusion gene only D V617F point mutation in JAK2 E 5q-Syndrome

Answer 1006

This patient exhibits features of chronic myeloid leukaemia as evidenced by raised myeloid lineage cells including neutrophils, myelocytes and basophils. The neutrophils are morphologically normal but cytochemically different – a laboratory test sometimes used to differentiate between reactive or leukaemoid neutrophilia and CML is the leukocyte alkaline phosphatase. It is normal or high in the former, but characteristically low in CML. Absolute basophilia is a universal finding in CML, with absolute eosinophilia found in 90 per cent of cases. A raised platelet count is also common in CML; a low platelet count, however, should make one reconsider the diagnosis, e.g. myelodysplastic syndromes

Question 1007

Which of the following patients has the worse prognosis? A 25-year-old man with inguinal lymphadenopathy B 25-year-old woman with mediastinal and inguinal lymphadenopathy C 25-year-old woman with mediastinal and inguinal lymphadenopathy and night sweats D 25-year-old woman with mediastinal and inguinal lymphadenopathy with 5 per cent weight loss in last 6 months E 25-year-old man with cervical and mediastinal lymphadenopathy

Answer 1007

This question relies on the candidate’s knowledge and understanding of the Ann Arbor staging system. This clinical staging system is relatively intuitive – stages are between I and IV either in the absence or presence of ‘B symptoms’. A simplified version of the classification is as follows: • Stage I: involvement of a single lymph node region • Stage II: involvement of two or more lymph node regions on the same side of the diaphragm • Stage III: involvement of lymph nodes on both sides of the diaphragm • Stage IV: extranodal spread (not spleen however, this is taken as a lymph node) The definition of B symptoms includes significant unexplained fever, night sweats or unexplained weight loss of over 10 per cent during 6 months prior to diagnosis Patient A would therefore be classified as Ia, patient B as IIa, patient C as IIIb, patient D as IIIa, technically as she does not quite fulfil the 10 per cent loss in 6 months and finally patient E as stage IIa. Note that in Hodgkin’s lymphoma, the disease always spreads contiguously whereas in non-Hodgkin’s lymphoma this is not always the case.

Question 1008

A patient presents with acute promyelocytic leukaemia. What is the most likely mechanism of underlying leukaemogenesis? A Telomere shortening B Aberrant fusion of two genes C Impaired protein degredation D Over-expression of cellular oncogene E Post-translational modification

Answer 1008

B Acute promyelocytic leukaemia is interesting for a number of reasons. There is a reciprocal translocation between the long arms of chromosomes 15 and 17 giving the PML-RARA fusion gene (B). This links the retinoic acid receptor alpha (RARA) gene on chromosome 17 with the promyelocytic leukaemia (PML) gene on chromosome 15. RARA is a member of a family of retinoin-binding transcription factors that regulate gene expression. It heterodimerizes with retinoid X receptor (RXR) and binds to retinoic acid response elements to influence gene transcription. In the absence of retinoic acid, the RARA/RXR dimer interacts with another protein (nuclear corepressor) to repress gene transcription. Therefore, addition of retinoic acid stimulates gene transcription. In the setting of promyelocytic leukaemia, retinoic acid induces myeloid differentiation which is abnormally halted thus providing remission by encouraging cell differentiation rather than cell death. The second reason this type of leukaemia is interesting is its association with disseminated intravascular coagulopathy. The pathogenesis is not completely understood but recognizing it early is important as treatment with retinoic acid plus supportive therapy can lead to rapid improvement in the coagulopathy.

Question 1009

A 16-year-old girl with mild von Willebrand’s disease is scheduled for a dental extraction. She has had one previously where she required two units of blood transfused. What is the most appropriate treatment for this patient prior to surgery? A Cryoprecipitate B Desmopressin C Fresh frozen plasma D Vitamin K E Recombinant factor VIII concentrate

Answer 1009

This woman has mild von Willebrand’s disease (vWD) which can be treated with desmopressin (B). There are three types of vWD – type I is a quantitative deficiency of von Willebrand Factor (vWF), type II is a qualitative defect in vWF whereas type III results in profound deficiency in vWF. There are four subtypes of type II vWF (2A, 2B, 2M and 2N). vWF is important in two ways; first it acts as a bridge between platelets and between platelets and subendothelial structures at the site of injury; and second it carries factor VIII which is a key molecule in the clotting cascade. Desmopressin acts to increase vWF and factor VIII concentration by encouraging its release from endothelial cell storage sites. Desmopressin is efficacious in type I and most type II disease but not in type III. This woman is known to have ‘mild’ disease thus making desmopressin a viable option Interestingly, desmopressin in patients with type 2B will lead to a transient worsening of their thrombocytopenia. Patients with type 2B vWD have increased binding of the abnormal vWF to platelets causing sequestration and clearance of platelets. This is worsened for desmopressin, if only for a few hours. Despite this, there have been reports of patients benefiting from desmopressin.

Question 1010

An 80-year-old man presents with tiredness and lethargy. After initial work-up, a diagnosis of myelodysplastic syndrome is suspected. Which of the following is true about this condition? A A blood film will typically show neutrophil toxic granulation B If there are 1 per cent blasts of the total white cell count, this represents leukaemic transformation C Cytotoxic chemotherapy is first line treatment D Mortality is more likely to be from infection than leukaemic transformation E Absence of the short arm of chromosome 5 is a subtype

Answer 1010

The myelodysplastic syndromes are a heterogeneous group of conditions characterized by an abnormal clone of stem cells with impaired proliferation and differentiation. The result is a peripheral cytopenia, qualitative abnormalities in erythroid, myeloid and megakaryocyte maturation, as well as increased risk of leukaemic transformation. The abnormalities, both quantitative and qualitative, in neutrophils mean susceptibility to bacterial infection is high and thus a corresponding increased likelihood of mortality (D). Skin infections are particularly common and resistant to treatment.

Question 1011

An 80-year-old man presents with tiredness and lethargy. After initial work-up, a diagnosis of myelodysplastic syndrome is suspected. Which of the following is true about this condition? A A blood film will typically show neutrophil toxic granulation B If there are 1 per cent blasts of the total white cell count, this represents leukaemic transformation C Cytotoxic chemotherapy is first line treatment D Mortality is more likely to be from infection than leukaemic transformation E Absence of the short arm of chromosome 5 is a subtype

Answer 1011

Absence of the long arm of chromosome 5 is a specific subtype of MDS. There is an interstitial deletion and it most commonly affects elderly women. It may respond quite dramatically to lenolidamide, a thalidomide derivative. Deletion of the short arm of chromosome 5 is associated with Cri du chat syndrome – a genetic disorder unrelated to MDS, named due to the characteristic cat cry made by affected children (‘cri du chat’ from French meaning ‘call of the cat’).

Question 1012

It affects children and teenagers and has a characteristic chromosomal translocation (t11;22)(q24;q12). It is negative for alkaline phosphatase and positive for CD99 (MIC2) immunostain. It is more commonly found in the pelvis and diaphysis/metaphysis of long bones than around the knee. Widespread metastases and bone marrow involvement are frequent.

Answer 1012

Ewing's sarcoma

Question 1013

usually affect older patients. The prognosis is variable depending on the grade of tumour. They usually grow slowly and not only affect long bones but also the ribs, spine and pelvis. The only treatment is surgical excision as both chemotherapy and radiotherapy are ineffective.

Answer 1013

Chondrosarcoma

Question 1014

are both spindle cell malignant tumours, arising from stromal cells and collectively they make up the majority of soft tissue sarcomas

Answer 1014

Fibrosarcomas and malignant fibrous histiocytomas

Question 1015

The most common presentation is pain and a mass, which occurs near a joint such as the knee, with the distal femur and proximal tibia being the most common sites. X-rays show a mixed sclerotic and lytic lesion in the metaphysis that may permeate the bone causing a soft tissue mass and a periosteal reaction. Bone formation within the tumour is characteristic of osteosarcoma and is usually visible on X-rays. Bone alkaline phosphatase has significant value in diagnosing

Answer 1015

Osteosarcoma

Question 1016

is a form of fibrosing lung disease that is chronic and progressive. It presents with shortness of breath and cough and is more likely to be seen in males over the age of 50. On histopathology, fibrosis and cyst formation are seen.

Answer 1016

Cryptogenic fibrosing alveolitis

Question 1017

These tumours, if well-differentiated, show keratin pearls and cell junctions (or desmosomes), which form the characteristic intercellular ‘prickles’.

Answer 1017

Squamous cell carcinoma

Question 1018

has a very close association with smoking and paraneoplastic syndromes and is very chemo-sensitive. They are poorly differentiated and the mutations commonly involved are p53 and RB1.

Answer 1018

SCLC

Question 1019

is a type of fibrosing lung disease or ‘dusty lung’ caused by inorganic dust inhalation. It commonly affects the upper lobes, while asbestosis affects the lower lobes more severely. It is an alteration of the lung structure rather than neoplastic differentiation of cells and is therefore unlikely to be the diagnosis for this patient.

Answer 1019

Pneumoconiosis

Question 1020

is a benign lesion that is rapidly growing and dome-shaped. It arises from the pilosebaceous glands and often resembles SCC. However, the growth of a keratoacanthoma retains its smooth surface, unlike an SCC and a malignant melanoma.

Answer 1020

Keratoacanthoma

Question 1021

presents as an enlarging well-demarcated erythematous plaque with an irregular border but non-elevated.

Answer 1021

Bowen's disease

Question 1022

of the skin begins as a small nodule that may become ulcerated and necrotic. Bleeding is quite common and the clinical presentation is highly variable.

Answer 1022

SCC

Question 1023

histopathology is spongiosis of epidermis and perivascular chronic inflammatory infiltrate in the dermis. Acanthosis (epidermal thickening) would develop if xx becomes chronic.

Answer 1023

Eczema

Question 1024

will commonly present with psoriatic nail lesions (pitting, onycholysis), dactylitis and tendinitis. X-rays will show ‘new fluffy’ bone.

Answer 1024

Psoriatic arthritis

Question 1025

a rheumatoid factor-seronegative, HLA B27-linked spondyloarthopathy commonly affecting the larger joints (e.g. sacroiliac and knee joints). Patients also sometimes develop circinate balanitis, keratoderma blenorrhagica and enthesitis of the Achilles tendon

Answer 1025

Reiter's syndrome (Reactive arthritis)

Question 1026

Macroscopically, the kidney is replaced by rounded masses of solid, fleshy, white lesions with vast amounts of necrosis. Microscopically, it is composed of four elements: immature-looking glomerular structures, primitive small cell blastaematous tissue, epithelial tubules and stroma composed of spindle cells and striated muscle.

Answer 1026

Wilm's dWT1

Question 1027

is a benign epithelial tumour composed of large cells with granular, eosinophilic cytoplasm filled with mitochondria. It has little necrosis or haemorrhage. It is a variant of renal adenoma and is often confused with renal cell carcinoma.

Answer 1027

Oncocytoma

Question 1028

Only xx papillomas can present with nipple discharge that is blood stained, while xxl papillomas can remain clinically silent.

Answer 1028

Central Peripheral

Question 1029

is a benign sclerosing lesion characterized by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue. They are common and usually present as stellate masses on screening mammograms.

Answer 1029

Radial scar

Question 1030

B1 to B5b grading

Answer 1030

* B1 = normal breast tissue. * B2 = benign abnormality (A) * B3 = lesion of uncertain malignant potential (B) * B4 = suspicious of malignancy (E) * B5 = malignant * B5a = ductal carcinoma in situ (C) * B5b = invasive carcinoma

Question 1031

is a failure of differentiation of metanephric tissues, it is typically asymptomatic and it is not hereditary in nature but developmental, therefore often presenting in childhood.

Answer 1031

Cystic renal dysplasia

Question 1032

is occasionally a familial condition that does not impair renal function and presents with renal stones predisposing to renal colic and infections.

Answer 1032

Medullary sponge disease

Question 1033

Meningitis in people with surgical shunts

Answer 1033

Staph aureus and gram negative rods are the most comon cause