haem

Question 1

What might you see on a blood film in these conditions: Abetalipoproteinaemia, liver disease, hypospenism. Histologist reports RBCs showing spicules of different sizes, shapes and distribution.

Answer 1

acanthocytes

Question 2

in what conditions might you see basophilic stippling?

Answer 2

small dots at the periphery are seen due to accelerated erythropoiesis or defective Hb synthesis

seen in

lead poisoning

megaloblastic anaemia

myelodysplasia

liver disease

haemoglobinapthy e.g. thalassaemia

Question 3

When might you see Burr Cells/ Echinocytes?

Answer 3

PUGS

Pyruvate Kinase Deficiency

Uraemia

GI bleed

Stomach carcinoma

Question 4

Heinz bodies are assoc with?

Answer 4

***G6PD deficiency

glucose 6 phosphate dehydrogenase

+

chronic liver disease

Question 5

Howell-Jolly bodies assoc with?

Answer 5

Post splenectomy/ Hyposplenism

e.g in sickle cell disease, coeliac disease, congenital, UC/ Crohns, myeloproliferative disease, amyloid

megaloblastic anaemia,

hereditary spheroctosis

Question 6

Which of these anomalies would you not see on a blood film of a patient with megaloblastic anaemia?

a) basophilic stippling
b) target cells- codocytes
c) howell-jolly bodies
d) hypersegmented polymorphs (right shift)

Answer 6

codocytes

these are cells with bulls eye appearance in central pallor. and are seen in iron deficiency anaemia rather than megaloblastic anaemia

all other features may be seen on blood film

Question 7

pelger huet cells associated with?

Answer 7

congenital (lamin B receptor mutation)

Acquired (called Pseudo pelger huet cells):

myelodysplastic syndromes

AML

CML

Question 8

What is the definition of anaemia in males and females?

Answer 8

males: <13.5g/dL (<135g/L)
females: <11.5 g/dL (<115g/L)

Question 9

Signs and symptoms of anaemia?

Answer 9

symptoms:

lethargy, SOB, faintness, palpitations, headaches, tinnitus, anorexia

Signs:

pallor (in severe anaemia), tachycardia, flow murmurs

Question 10

causes of microcytic anaemia

Answer 10

Iron deficiency Anaemia

Anaemia of chronic disease

Thalassaemia

sideroblastic anaemia

Lead poisoning

Question 11

Causes of normocytic anaemia

Answer 11

Acute blood loss

Anaemia of chronic disease

Pregnancy

Haemolysis

Renal failure

Bone marrow failure

Question 12

what is sideroblastic anaemia?

Answer 12

a form of anaemia in which BM produces ringed sideroblasts rather than normal erythrocytes.

in sideroblastic anaemia, the body has iron available but cannot incorporate it into Hb

-> iron buildup in organs such as liver, heart, spleen, kidney can lead to organ failure/ damage

Question 13

what ferritin/ Fe/ TIBC/ Transferrin results would you see in a patient with sideroblastic anaemia?

Answer 13

High ferritin

High Fe

High transferrin saturation

Normal/ Low TIBC

Question 14

causes of macrocytic anaemia

Answer 14

FATRBC

Folate deficiency

Antifolates e.g. phenytoin, methotrexate

Thyroid- hypothyroidism

Reticulocytosis - release of immature cells e.g. w haemolysis

B12 deficiency

Cirrhosis (alcohol excess/ liver disease)

myelodysplastic syndromes

Question 15

a microcytic, hypochromic anaemia with anisocytosis and polikilocytosis + pencil cells

on examination, you find koilonychia, atrophic glossitis, angular cheilosis, post-cricoid webs, brittle hair and nails

what is it?

Answer 15

iron deficiency anaemia

causes: always bleeding until proven otherwise

Question 16

what Iron/ Ferritin/ TIBC/ Transferrin levels will you see in iron deficiency anaemia?

Answer 16

low Fe

Low ferritin

High TIBC

High Transferrin

Question 17

causes of iron deficiency anaemia

Answer 17

Blood loss:

GI loss

menorrhagia

peptic ulcer/ gastritis

meckels diverticulum

polyps/ colorectal Ca

Increased utilisation:

Pregnancy/ lactation

children/ infants

decreased intake:

suboptimal diet

decreased absorption:

coeliac disease

post gastric surgery

intravascular haemolysis:

paroxysmal nocturnal haemoglobuniria

MAHA

-> chronic loss of Hb in urine

Question 18

NICE guidelines for IDA with no obvious cause?

Answer 18

OGD + colonoscopy

urine dip

coeliac investigations

Question 19

IDA mx?

Answer 19

treat the cause

oral Iron

if severe, IV iron

Question 20

what are some side effects of oral iron?

Answer 20

black stools

nausea

abdo discomfort

diarrhoea/ constipation

Question 21

IL6, cytokine- driven inhibition of red cell production

ferritin is high.

Fe sequestered in macropahges to deprive invading bacteria of Fe

Answer 21

anaemia of chronic disease

e.g.

with chronic infection (TB)

vasculitis (chronic inflammation)

rheumatoid arthritis

malignancy

Question 22

Ringed sideroblasts seen in bone marrow:

erythroid precursors with iron deposited in mitochondria in a ring around the nucleus

On peripheral blood smear: basophilic stippling (cytoplasmic granules of RNA precipitates) and Pappenheimer bodies (cytoplasmic granules of iron)

what condition?

Answer 22

sideroblastic anaemia

Question 23

Causes of Sideroblastic anaemia

Answer 23

myelodysplastic syndrome

e.g. refractory anaemia with ringed sideroblasts

excessive alcohol use (most common cause- and reversible!)

B6 pyridoxine deficiency (e.g. isoniazid tx)

lead posioning

copper deficiency

Question 24

Tx of sideroblastic anaemia

Answer 24

if severe, may need transfusion

treat the cause

and Pyridoxine (Vit B6)

Question 25

what are the fe/ ferritin/ TIBC levels in haemochromatosis?

Answer 25

high Fe high Ferritin Low/ N TIBC

Question 26

how does ferritin change with inflammation/ infection/ malignancy

Answer 26

ferritin is an acute phase protein and increases with inflammation/ infection/ malignancy

Question 27

what are the causes of megaloblastic anaemia?

Answer 27

Vit B12/ folate deficiency or cytotoxic drugs e.g. antifolates

Question 28

most common cause of macrocytosis without anaemia?

Answer 28

alcohol

Question 29

what are some blood film findings with megaloblastic anaemia?

Answer 29

hypersegmented neutrophils increased MCV (macrocytosis) anaemia thrombocytopenia Howell-Jolly bodies

Question 30

Causes of Vit B12 deficiency

Answer 30

normal sources of B12: meat and dairy products Dietary: vegans Malabsorption: stomach (pernicious anaemia/ post gastrectomy) terminal ileum (crohns/ tropical sprue/ ileal resection)

Question 31

anaemia with glossitis, angular cheilosis + dementia, depression, psychosis + peripheral neuropathy, parasthesiae what is the condition?

Answer 31

b12 deficiency anaemia

Question 32

loss of vibration and proprioception in hands, absent ankle reflex in vit B12 deficiency what is this?

Answer 32

peripheral neuropathy

Question 33

what may develop in a patient with vit b12 deficiency, where weakness, numbness and tingling in peripheries progressively worsens

Answer 33

subacute combined degeneration of the spinal cord prolonged deficiency leads to irreversible nervous system damage. patchy losses of myelin in the dorsal and lateral columns. patients present with weakness of legs, arms, trunk, tingling and numbess that progressively worsens. vision changes and change of mental state may be present. bilateral spastic paresis may develop Babinskis may be +ve

Question 34

treatment of vit b12 deficiency?

Answer 34

replace the Vit B12 IM Hydroxocobalamin

Question 35

investigation for pernicious anaemia?

Answer 35

anti-parietal cell antibodies (90%) anti-IF antibodies (50%) Schilling test (outdated)

Question 36

causes of folate deficiency

Answer 36

source of folate: leafy green vegetables, nuts, liver causes: poor diet increased demand: pregnancy, increased cell turnover (malignancy, haemolysis etc) malabsorption: coeliac, tropical sprue drugs: alcohol, antiepileptics (phenytoin), methotrexate, trimethoprim

Question 37

folate deficiency treatment?

Answer 37

oral folic acid only give if cause of anaemia is known, as folic acid may exacerbate neuropathy of B12 deficiency

Question 38

normal life span of RBCs

Answer 38

120 days

Question 39

features of all haemolytic anaemias

Answer 39

increased unconjugated Bilirubin increased reticulocytes (increased MCV, polychromatosis) increased urobilinogen increased LDH may have pigmented gallstones

Question 40

features of extravascular haemolytic anaemia

Answer 40

removal by reticuloendothelial system - splenomegaly

Question 41

features of intravascular haemolysis

Answer 41

increased free plasma Hb decreased Haptoglobin (binds free Hb) haemoglobuniura (dark red urine) methaemalbuminaemia (haem + albumin in blood)

Question 42

causes of inherited haemolytic anaemia

Answer 42

membrane defect: hereditary spherocytosis hereditary elliptocytosis enzyme defect: G6PD deficiency Pyruvate Kinase deficiency Haemoglobinopathies: Sickle Cell disease thalassaemias

Question 43

coinheritance of what condition further increases risk of cholelithiasis in chronic haemolytic anaemia?

Answer 43

Gilberts Syndrome

Question 44

Causes of acquired haemolytic anaemia

Answer 44

Immune: autoimmune haemolytic anaemia (warm/ cold) alloimmune- haemolytic transfusion reactions non-immune: Microangiopathic haemolytic anaemia Mechanical e.g. metal valves, trauma Paroxysmal nocturnal haemoglobinuria infections (e.g Malaria), drugs

Question 45

deficiency of what enzyme in Gilbert's syndrome?

Answer 45

UDP-glucuronosyl transferase 1

Question 46

hereditary spherocytosis - what inheritance pattern - what membrane protein is defective/ deficient - diagnostic tests

Answer 46

Autosomal dominant (25% are auto recessive or de novo) Spectrin (most common) or ankyrin or protein 4.2/ band 3 deficiency/defect diagnosis via osmotic fragility test (increased lysis in hypotonic solutions), -ve coombs test, spherocytes on blood film, eosin-5-maleimide (decreased binding)

Question 47

pallor, jaundice, splenomegaly, pigmenturia bloods show increased Br, increased LDH and decreased/absent haptoglobins Blood film shows spherocytes Osmotic fragility positive and decreased binding of dye eosin-5-maleimide

Answer 47

Hereditary spherocytosis

Question 48

what complications may occur with hereditary spherocytosis? increased susceptibility to?

Answer 48

aplastic anaemia with parvovirus B19 infection develop gallstones due to increased uric acid production -\> calcium bilirubinate gallstones increased iron overload/ osteoporosis

Question 49

treatment of hereditary spherocytosis

Answer 49

splenectomy - definitive treatment folic acid due to increased folate demand

Question 50

hereditary elliptocytosis - inheritance pattern - mutation in which protein

Answer 50

almost all are autosomal dominant spectrin mutations most common severity ranges from asymptomatic to hydrops fetalis

Question 51

a severe form of elliptocytosis that is autosomal recessive abnormal sensitivity of red blood cells to heat spectrin deficiency

Answer 51

hereditary pyropoikilocytosis

Question 52

a hereditary haemolytic anaemia where RBC is oval-shaped. defect lies in band 3 protein. greater robustness of cells to osmotic pressures/ temp changes resistance to infected by plasmodium falcuparum common in malaysia and papau new guinea

Answer 52

southeast asian ovalocytosis

Question 53

pyruvate kinase deficiency - most common inheritance pattern - what pathway does it affect

Answer 53

autosomal recessive pyruvate kinase converts phosphoenol pyruvate + ADP -\> ATP + pyruvate so in pyruvate kinase deficiency, low ATP and pyruvate

Question 54

may only present at times of stress e.g. pregnancy and infections symptoms from birth, limited to or most severe during childhood. autosomal recessive condition mild-severe haemolytic anaemia severe neonatal jaundice splenomegaly Blood film showing echinocytes

Answer 54

Pyruvate Kinase deficiency

Question 55

what shifts the oxygen dissociation curve to the right? reduced affinity of Hb to O2

Answer 55

pyruvate kinase deficiency (causes increased 2-3 DPG aka 2-3 BPG) increased temp low pH high CO2

Question 56

G6PD deficiency - inheritance pattern - what pathway is affected

Answer 56

X linked commonest RBC enzyme defect G6PD catalyzes 1st step in pentose phosphate pathway - generates NADPH required to maintain intracellular glutathione. glutathione protects RBCs from oxidant damage. low glutathione in G6PD deficiency -\> susceptibility to oxidant damage e.g drugs, fava beans, acute infections, acute stressors

Question 57

rapid anaemia and jaundice, with blood film showing Heinz bodies and bite cells precipitated by drugs like primaquine, sulfonamides, nitrofurantoin, aspirin, broad beans/ favism, acute infections, moth balls

Answer 57

G6PD deficiency

Question 58

treatment of G6PD deficiency

Answer 58

avoid precipitants if severe- transfuse genetic screening folic acid supplementation immunisations against blood borne viruses (Hep A/B) cholecystectomy for symptomatic gallstones splenectomy if indicated

Question 59

does G6PD deficiency cause intravascular or extravascular deficiency?

Answer 59

intravascular haemolysis - causes dark urine

Question 60

what are some oxidants causing acute episodes of G6PD deficiency?

Answer 60

fava beans antimalarials e.g. primaquine antibiotics e.g. sulfonamide, nitrofurantoin infections moth balls

Question 61

what would be see on blood film in G6PD deficiency

Answer 61

Heinz bodies (inclusions within RBC composed of denatured Hb) and Bite cells (caused by splenic removal of denatured Hb)

Question 62

diagnosis of G6PD deficiency

Answer 62

G6PD enzyme assay 2-3 months after a crisis

Question 63

Sickle Cell Disease - pattern of inheritance - what is the mutation

Answer 63

autosomal recessive single base mutation GAG-\> GTG Glu -\> Valine at codon 6 of beta chain HbA -\> HbS HbSS: sickle cell anaemia HbAS - sickle cell trait

Question 65

when does sickle cell anaemia manifest? (at what age)

Answer 65

3-6 months coinciding with decreasing fetal Hb HbF

Question 66

symptoms of a child with sickle cell anaemia

Answer 66

Hand-foot syndrome: dactylitis painful crises stroke acute chest syndrome \*\*\*Splenic sequestration- can lead to severe anaemia, shock and death very susceptible to bacteraemia- due to immature immune system parvovirus B19 may lead to aplastic crisis

Question 67

what is splenic sequestration and when is it most likely to happen?

Answer 67

splenic sequestration is the acute pooling of a large proportion of circulating RBCs in the spleen spleen enlarges acutely Hb falls acutely and death can occur doesnt happen in older children because recurrent infarction has left the spleen small and fibrotic occurs most commonly in children 1-3 yrs old

Question 68

sickle cell anaemia management in a child

Answer 68

analgesia for painful crises \*\*Folic acid - hyperplastic erythropoiesis, growth sports Penicillin V + Pneumovax + HiB vaccine Carotid doppler monitoring in early childhood with prophylactic exchange transfusion if turbulent carotid flow Hydroxycarbamide to prevent sickling crises

Question 69

what complication of sickle cell anaemis is more common in adults than in children: 1. hand foot syndrome 2. hyposplenism 3. red cell aplasia 4. splenic sequestration 5. stroke

Answer 69

hyposplenism

Question 70

siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count- likely diagnosis? 1. splenic sequestration 2. Parvovirus B19 infection 3. Folic acid deficiency 4. Haemolytic crisis 5. Vit B12 deficiency

Answer 70

Parvovirus B19

Question 71

A 6 year old Afro Caribbean boy presents with chest and abdo pain Hb is 63g/L, MCV 85 fl and blood film shows sickle cells likely diagnosis? 1. sickle cell trait 2. sickle cell anaemia 3. sickle cell/ beta thalassaemia

Answer 71

sickle cell anaemia in sickle cell trait- usually asymptomatic except under stress

Question 72

complications of sickle cell anaemia that usually presents in adults

Answer 72

hyposplenism - small fibrotic spleen or no spleen if post splenectomy chronic kidney disease retinopathy pulmonary HTN mesenteric ischaemia

Question 73

complications of sickle cell anaemia in teenage years

Answer 73

impaired growth gallstones priapism - persistent painful erection

Question 74

Beta Thalassaemia - inheritance pattern - mutation in what gene

Answer 74

Autosomal recessive mutation in the HBB gene on chr 11 -\> decreased beta chain synthesis and excess alpha chains Increased HbA2 and HbF seen B thal major: Skull bossing, maxillary hypertrophy, hairs on end skull Xray Hepatosplenomegaly

Question 75

Skull bossing, maxillary hypertrophy, hairs on end skull Xray Microcytic anaemia increased % of HbA2

Answer 75

thalassaemia major

Question 76

how does b thalassaemia minor present

Answer 76

asymptomatic carrier mild anaemia

Question 77

when and how does b thalassaemia major present?

Answer 77

at 3-6 months as HbF falls severe anaemia FTT hepatosplenomegaly due to extramedullary erythropoiesis bony deformity heart failure

Question 78

Diagnosis of B thalassaemia

Answer 78

Guthrie card test Hb electrophoresis

Question 79

Treatment of beta thalassaemia

Answer 79

Blood transfusions + Desferrioxamine Folic acid Bone marrow transplant may offer possibility of cure in young ppl w HLA-matched donor

Question 80

what is this

Answer 80

hereditary spherocytosis

Question 81

what is this

Answer 81

hereditary elliptocytosis

Question 82

what is this

Answer 82

sickle cell anaemia

Question 83

what is shown on this blood film likely diagnosis?

Answer 83

Bite cells G6PD deficiency

Question 84

what is shown in this blood film likely diagnosis?

Answer 84

G6PD deficiency Heinz bodies

Question 85

what are the two most important acquired haemolytic anaemias in children?

Answer 85

autoimmune haemolytic anaemia Haemolytic uraemic syndrome

Question 86

prognosis of alpha thalassaemia trait (2) HbH disease (3 alpha chains deleted) Alpha thal major (4 deleted)

Answer 86

alpha thal trait -\> asymptomatic, mild anaemia HbH disease -\> moderate anaemia, hepatosplenomegaly. microcytic hypochromic anaemia w target cells and Heinz bodies Alpha major: incompatible with life. hydrops fetalis

Question 87

secondary causes of a true polycythaemia

Answer 87

Raised EPO due to Renal Cell Carcinoma HCC Bronchial Ca High Altitude Cyanotic Heart disease Hypoxic Lung disease

Question 88

+ve direct antiglobulin test (coombs) increased Br, increased LDH blood film shows spherocytes assoc with CLL, SLE, lymphoma, drugs like methyldopa/ penicillin what condition?

Answer 88

warm AIHA - autoantibodies IgG binds to RBCs at 37 degrees

Question 89

what type of autoantibody in cold AIHA?

Answer 89

IgM

Question 90

what type of autoantibody in warm AIHA?

Answer 90

IgG

Question 91

management of warm AIHA

Answer 91

steroids splenectomy if indicated immunosuppression

Question 92

positive coombs test Raynaud's phenomenon assoc w lymphoma, EBV, mycoplasma infections what condition?

Answer 92

Cold AIHA IgM binds to RBC \<37 degrees

Question 93

Tx of cold AIHA

Answer 93

treat underlying condition avoid the cold

Question 94

what antibodies are associated with paroxysmal cold haemoglobinuria?

Answer 94

Donath-Landsteiner antibodies

Question 95

Haemoglobinuria (dark red/ brown urine) after exposure to cold temperatures + often after infection e.g measles, syphilis, VZV

Answer 95

Paroxysmal cold haemoglobinuria can occur when blood passes through cold extremities in cold weather. when blood returns to the warmer central circulation, the RBCs are lysed with complement, causing intravascular haemolysis -\> haemoglobinuria and anaemia

Question 96

Paroxysmal cold haemoglobinuria - what is the autoantibody involved - what infections may typically trigger this?

Answer 96

Donath-Landsteiner antibodies aka polyclonal IgG anti-P autoantibody assoc w syphilis, post viral infection (measles, mumps, influenza etc), mycoplasma/ h influenzae

Question 97

the only acquired intrinsic defect in the cell membrane leading to haemolytic anaemia

Answer 97

paroxysmal noctural haemoglobinuria

Question 98

red urine most pronounced in the morning (when urine is more concentrated) + tiredness, SOB, palpitations Bloods show low Hb, raised LDH, raised Br, decreased Haptoglobin, raised reticulocytes Hams test +ve

Answer 98

paroxysmal nocturnal haemoglobinuria

Question 99

Paroxysmal nocturnal haemoglobinuria - where is the defect - what happens

Answer 99

acquired defect of surface protein CD55 on the RBC - \> complement cascade attacks the RBCs - \> intravascular haemolysis

Question 100

Diagnostic tests for Paroxysmal nocturnal haemoglobinuria

Answer 100

GOLD standard is flow cytometry for CD55 and CD59 on white and red blood cells Hams test: RBCs placed in mild acid, a positive result (increased RBC fragility) is suggestive (low sensitivity and specificity)

Question 101

complications / common symptoms of Paroxysmal nocturnal haemoglobinuria

Answer 101

\*\*increased risk of thrombosis esp in hepatic vein -\> budd-chiari syndrome portal vein -\> portal vein thrombosis mesenteric ischaemia cerebral venous thrombosis

Question 102

tx for Paroxysmal Nocturnal Haemoglobinuria?

Answer 102

Acute attacks: Iron/ folate supplements if needed thromboprophylaxis with warfarin eculizumab - a monoclonal antibody that prevents complement from binding RBCs

Question 103

pentad of TTP

Answer 103

MAHA low Pl Fever Neuro+ Nephro impairment

Question 104

what is going on in TTP that causes the features of MAHA, low Pl, fever, and neuro and kidney impairment?

Answer 104

TTP is a rare disorder of the blood coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body - \> autoimmune condition: autoantibody inhibits enzyme that cleaves vWF. this leads to excessive vWF and pl adhesion/activation - \> consumption of pl leads to low Pl - \> these thrombi can cause damage to many organs including the kidneys, heart, brain, CNS (fatality rate used to be 95% before plasma exchange!!!)

Question 105

Tx of TTP

Answer 105

plasmapheresis - exchange transfusion of patients blood plasma + corticosteroids + rituximab + maybe additional immunosuppressants e.g. vincristine, cyclophosphamide, splenectomy

Question 106

what is the triad of haemolytic uraemic syndrome?

Answer 106

Haemolytic anaemia Acute kidney failure (uraemia) thrombocytopenia

Question 107

Haemolytic Uraemic syndrome - most common cause - most common age group

Answer 107

E coli O157:H7 which causes a preceding episode of infectious bloody diarrhoea (can also be Shigella/ campylobacter) HUS is a medical emergency!!! most common cause of acquired acute renal failure in childhood. 30% may suffer residual renal injury the primary target is the vascular endothelial cell. Shiga-toxin-activated endothelial cells then become thrombogenic -\> MAHA + low Pl

Question 108

what is the primary target in Haemolytic Uraemic Syndrome that underlies the symptoms?

Answer 108

renal vascular endothelial cells

Question 109

Microangiopathic Haemolytic Anaemia: how are RBCs destroyed? what will investigations show? what are some common causes?

Answer 109

endothelial layer of small vessels damaged -\> fibrin deposition and pl aggregation -\> RBCs forced through fibrin mesh causing mechanical RBC destruction/ fragmentation Blood film- shistocytes Causes: HUS DIC TTP Malignancy HELLP syndrome SLE (due to Immune complexes aggregating w platelets, forming intravascular thrombi) Eclampsia

Question 110

what factors make up the intrinsic pathway?

Answer 110

12 11 9 (8) - fVIIIa that converts X-\>Xa alongside IXa 10 \* rmb the next factor starts with the last letter of the previous factor!

Question 111

what factors are involved in the extrinsic pathway?

Answer 111

Tissue factor 7 TF + fVIIa converts X -\> Xa

Question 112

what factors / components make up the final common pathway of the clotting cascade?

Answer 112

Xa (from intrinsic/ extrinsic pathway) + fVa convert prothrombin -\> thrombin (IIa) IIa converts Fibrinogen -\> Fibrin XIIIa converts FIbrin -\> fibrin clot Plasmin degrades fibrin clot into fibrin degradatin products

Question 113

Plasmin What is it and what does it do? How is it formed? What inhibits plasmin?

Answer 113

Plasmin is a serine protease that acts to dissolve fibrin blood clots Tissue plasminogen activators convert Plasminogen -\> plasmin Plasmin is inhibited by alpha 2 anti plasmin and alpha 2 macroglobulin

Question 114

what is the first step of forming the haemostatic plug?

Answer 114

platelet adhesion either by binding directly to exposed collagen via gpIa or to vWF via gpIb

Question 115

how do you monitor warfarin therapy? which pathway does it look at?

Answer 115

Prothrombin Time - Extrinsic Pathway

Question 116

what is the next step in forming a haemostatic plug after platelet adhesion?

Answer 116

Platelet aggregation expression of gpIIb/IIIa on pl surface

Question 117

what is the step after platelet aggregation in the process of forming a haemostatic plug?

Answer 117

Fibrinogen binding then forming a stable fibrin clot through a thrombin (fIIa) burst

Question 118

Thromboxane A2 / Prostacyclin PgI2 which one increases and which one inhibits platelet aggregation?

Answer 118

Thromboxane A2 - prothrombotic Prostacyclin PgI2- inhibits platelet aggregation

Question 119

what are protein C and protein S?

Answer 119

Protein C and protein S (cofactor) proteolytically inactivate fVa and fVIIIa

Question 120

what does Tissue Factor Pathway Inhibitor do?

Answer 120

antithrombotic TFPI can reversibly inhibit fXa

Question 121

what does Antithrombin III do what drug influences this?

Answer 121

Antithrombin III inactivates thrombin, fXa and fIXa Heparin increases Antithrombin III activity

Question 122

how to monitor final common pathway?

Answer 122

thrombin time

Question 123

how to assess intrinsic pathway? when do you use it?

Answer 123

APTT to monitor unfractionated Heparin therapy

Question 124

auto dominant genetic condition leading to abnormal blood vessel formation in skin, mucous membranes and in lung, liver, brain. telangiectasia - may occur on skin, mucosal linings of nose and GI tract nosebleeds extremely common arteriovenous malformations in lungs (haemoptysis/ haemothorax), liver, brain (haemorrhage)

Answer 124

Osler-Weber-Rendu Aka Hereditary Haemorrhagic telangiectasia

Question 125

presentation of coagulation disorders vs platelet disorders/ vascular defects

Answer 125

Platelet disoders/ vascular defects - superficial bleeding into skin, mucosal membranes - bleeding immediate after injury/ surgery - petechiae - small, superficial bruises vs Coagulation disorders - bleeding into deep tissue, muscles, joints - delayed, but often severe bleeding after injury - bleeding often prolonged - large deep bruises (ecchymoses)

Question 126

low Platelet count, purpuric rash, petechiae, blood blisters in mouth increased tendency to bleed-\> bleeding from nostrils/ gums + menorrhagia acute, usually following an infection, usually spontaneously remits within 2 months

Answer 126

autoimmune thrombocytopenic purpura anti pl antibodies (IgG) against gpIIb/IIIa treatment with careful observation in mild cases. if v low pl counts/ significant bleeding: tx w corticosteroids, IVIG, imunosuppressive drugs or even platelet transfusions.

Question 127

Tx of low Platelet count in autoimmune thrombocytopenic purpura - if 20-50000 platelet count + not bleeding? - if 20-50000 platelet count + bleeding? - if \<20000, and not bleeding? - if \<20000 + bleeding

Answer 127

20-50000 platelet count + not bleeding: No tx 20-50000 platelet count + bleeding: steroids, IVIG - if \<20000, and not bleeding: steroids - if \<20000 + bleeding: steroids, IVIG, hospitalization

Question 128

Acute ITP vs Chronic ITP - usual age - preceding infection present? - onset of symptoms - platelet count at presentation - duration - spontaneous remission?

Answer 128

Acute vs Chronic ITP - children (2-6 yrs) vs Adults - chronic ITP usually affects women - preceding infection common in acute ITP - abrupt onset in acute ITP but onset can be abrupt- indolent with chronic ITP - platelets \< 20000 at presentation w acute/ vs \<50000 w chronic ITP - acute ITP usually 2-6 weeks and spontaneously remits whereas chronic is long term and assoc w other autoimmune diseases, and is unlikely to remit.

Question 129

features of extramedullary haemopoiesis

Answer 129

hepatosplenomegaly

Question 130

consequences of haemolytic anaemia

Answer 130

* Anaemia(+/-) as bone marrow may compensate * Erythroid hyperplasia with increased rate of red cell production and circulating reticulocytes * Increased folate demand * Susceptibility to effect of parvovirus B19 - can cause aplastic anaemia in patients with haemolytic anaemia who already have RBC with very low lifespan. * Propensity to gallstones(cholelithiasis) - due to increased generation of bilirubin * Increased risk of: iron overload (irrespective of transfusion due to increased intestinal absorption), osteoporosis

Question 131

why does LDH increase during haemolytic anaemia?

Answer 131

LDH is a glycolytic enzyme inside RBCs- and is thus, a sensitive marker of intravascular heamolysis

Question 132

whats the difference where the protein defect is between hereditary spherocytosis and hereditary elliptocytosis?

Answer 132

hereditary spherocytosis: vertical interaction hereditary elliptocytosis: horizontal interaction

Question 133

what is Pyrmidine 5 nucleotidase deficiency? what is seen on blood film?

Answer 133

Pyrimidine 5 nucleotidase removes pyrimidine - which is toxic to RBCs Blood film will show basophilic stippling seen in lead poisoning as lead is a significant inhibitor of the enzyme pyrimide 5 nucleotidase.

Question 134

when should you do a splenectomy in a child?

Answer 134

transfusion dependent signs of growth delay physical limitation Hb\<8g/dL hypersplenism do not perform before 3 years of age ideally perform before 10 years to maximise prepubertal growth

Question 135

what malignancies may result in iron deficiency?

Answer 135

GI cancers- gastric, colon, rectal Urinary tract ca- Renal cell carcinoma, Bladder Ca

Question 136

Leucoerythroblastic anaemia - what is it - what features on blood film?

Answer 136

leucoerythroblastic anaemia is any anaemic condition resulting from space occupying lesions in the bone marrow e.g. bone mets the circulating blood contains immature cells of the granulocytic series and nucleated RBCs Blood film shows teardrop RBCs, aniso/ poikilocytosis, nucleated RBCs, immature myeloid cells

Question 137

what are some causes of leucoerythroblastic anaemia?

Answer 137

marrow infiltrative disorders include: myelomas malignancy (any, breast, prostate, lung, leukaemia, lymphoma) myelofibrosis (massive splenomegaly, dry tap on BM aspirate) severe infection: TB, severe fungal infection

Question 138

what are some causes of neutrophilia?

Answer 138

corticosteroids may transiently cause rise in neutrophil blood levels underlying neoplasia tissue inflammation e.g. colitis, pancreatitis myeloproliferative/ leukaemic disorders localised and systemic infections: actue bacterial, fungal, certain viral infections

Question 139

how to differentiate between reactive/ malignant neutrophilia on blood film

Answer 139

reactive neutrophilia: presence bands, toxic granulation and signs of infection/ inflammation in malignancy: neutropenia + myeloblasts (AML) neutrophilia + basophilia + immature cells suggest CML

Question 140

Eosinophilia: what are some causes of reactive eosinophilia

Answer 140

o Parasitic infestation o allergic diseases e.g. asthma, rheumatoid, polyarteritis nodosa, pulmonary eosinophilia. o Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia) o Drugs (reaction erythema mutiforme)

Question 141

what malignant condition sees a monocytosis?

Answer 141

chronic myelomonocytic leukaemia infectious causes that cause a monocytosis include TB and brucella

Question 142

what are some causes of basophilia?

Answer 142

pox viruses CML

Question 143

Smear cells seen in?

Answer 143

CLL (most often assoc w abnormally fragile lymphocytes)

Question 144

Bone marrow infiltration causes what changes to blood film?

Answer 144

leucoerythroblastic picture immature myeloid cells nucleated RBCs teardrop RBCs

Question 145

Lymphoma - what is it? - where may it be found?

Answer 145

Lymphomas are neoplastic tumours of lymphoid cells. usually found in lymph nodes, bone marrow and or blood (via the lymphatic system) and in lymphoid organs such as the spleen, MALT

Question 146

why are lymphocytes particularly at risk of neoplasm/ malignancy?

Answer 146

rapid cell proliferation in immune response risks DNA replication error dependent on apoptosis (in the germinal centre) -\> apoptosis may get switched off in the germinal centre, there may be acquire DNA mutations in the pro apoptotic genes DNA molecules are cut and rejoined and undergo deliberate point mutation to generate immunoglobulin and T cell receptor diversity -\> potential for recombination errors and new point mutations

Question 147

Gastric MALToma what causes the chronic antigenic stimulation that may lead to gastric MALToma

Answer 147

Helicobacter pylori -\> marginal zone non-hodgkins lymphoma of the stomach

Question 148

Known risk factors of lymphoma:

Answer 148

constant antigenic stimulation (will increase risk of DNA replication error) infection (direct viral infection of lymphocytes e.g. EBV) loss of T cell function (e.g. HIV)

Question 149

what causes constant antigenic stimulation that may result in marginal zone lymphoma of the thyroid gland?

Answer 149

Hashimoto's Disease

Question 150

What causes chronic antigenic stimulation that may predispose to developing parotid lymphoma?

Answer 150

Sjogren's syndrome -\> marginal zone non-hodgkins lymphoma of the parotids

Question 151

a lymphoma caused by HTLV-1 infection HTLV-1 infects T cells common in the Carribean and Japanese population what lymphoma is associated?

Answer 151

Adult T cell leukaemia/ lymphoma \*nuclei of ATL cells have characteristic cloverleaf appearance

Question 152

what causes constant antigenic stimulation, predisposing the patient to small bowel T cell lymphoma?

Answer 152

Coeliac disease -\> enteropathy associated T-cell Non-Hodgkins Lymphoma (EATL)

Question 153

what virus is associated with Adult T cell leukaemia/ lymphoma?

Answer 153

HTLV-1

Question 154

HIV and EBV infection - how may this lead to lymphoma?

Answer 154

EBV infects B lymphocytes and causes proliferation of EBV antigen expressing B cells Healthy carrier state dependent on T cells recognising EBV antigen expressing B cells in HIV -\> loss of normal T cells increases risk of B cell lymphoma! \*also seen in post transplant patients (post transplant lymphoproliferative disorder)

Question 155

what is the most common type of lymphoma?

Answer 155

B cell Non Hodgkins lymphomas | (80%)

Question 156

t(11;14)

Answer 156

Mantle Cell Lymphoma rmb Mant11e

Question 157

t(2;5)

Answer 157

Anaplastic large cell lymphoma

Question 158

Of the common B cell non-hodgkin lymphomas, which are high grade? which are low grade?

Answer 158

High Grade: V aggressive: Burkitt's Aggressive: Diffuse Large B cell, Mantle Cell Low Grade: Indolent- Follicular, small lymphocytic/ CLL, marginal zone lymphoma, mantle zone lymphoma

Question 159

an indolent, mostly incurable lymphoma. t(14;18) translocation bcl-2 gene overexpression -\> increased bcl-2 protein (prevents apoptosis in tumour cells) Histopathology shows follicular pattern. Morphology shows centroblasts and centrocytes. Blood smear may show buttock cells. Stains positive for B cell marker CD10. translocations at bcl6 could also be involved.

Answer 159

Follicular lymphoma (35% of all non hodgkins lymphoma) Tx: watch and wait or if needed, rituximab- cyclophosphamide, vincristine, prednisolone

Question 160

Histopath shows small lymphocytes, naive or post germinal centre memory B cells, CD5+, CD23+ (abnormal markers) Indolent, but can undergo richter transformation

Answer 160

Small lymphocytic leukaemia / CLL

Question 161

CLL vs SLL?

Answer 161

CLL and SLL are essentially the same disease process with slightly different presentations - CLL is primarily seen in the BM, SLL in the LNs they are both lymphoproliferative diseases that mainly affect the elderly (mean age 65-70)

Question 162

MALT (mucosal associated lymphoid tissue) lymphoma / Marginal zone NHL - what sites are normally affected? - treatment?

Answer 162

mainly at extranodal sites. e.g. gut, lung, spleen, thyroid, parotid arise in response to chronic antigen stimulation treatment involves removing the antigenic stimulation e.g. H pylori eradication

Question 163

what is the H pylori triple therapy for eradication?

Answer 163

omeprazole, clarithromycin and amoxicillin

Question 164

Male predominance, lymph nodes affected, GI tract or disseminated disease at presentation t(11;14) Cyclin D1 overexpression/ dysregulation median survival rate 3-5 years Histology may show angular nuclei

Answer 164

Mantle Cell lymphoma an aggressive NHL Tx involves Rituximab-CHOP Auto-SCT for relapse maintenance rituximab delays the time to next progression

Question 165

what is overexpressed in Mantle Cell lymphoma?

Answer 165

Cyclin D1

Question 166

Mandibular mass/ abdo mass in children/ young adults EBV associated histology shows germinal centre cell origin with starry sky appearance t(8;14) - c-myc oncogene translocation can be detected using FISH stain aggressive disease

Answer 166

Burkitts lymphoma

Question 167

what virus is most commonly associated with burkitt's lymphoma?

Answer 167

EBV

Question 168

in Burkitt's lymphoma, what oncogene is overexpressed?

Answer 168

c-myc

Question 169

What immunodeficiency is associated with burkitts lymphoma?

Answer 169

HIV / post transplant patients

Question 170

richter's transformation: history of B cell CLL/ hairy cell laukaemia Histology shows "sheets of large lymphoid cells"

Answer 170

Diffuse Large B Cell lymphoma (DLBCL) (30-40% of NHL) aggressive tx: rituximab-CHOP (6-8 cycles) Auto-SCT for relapse aim of tx is curative

Question 171

affects middle aged/ elderly \*Large T cell lymphocytes Aggressive Often with associated reactive cell population esp eosinophils Lymphadenopathy and extranodal sites

Answer 171

Peripheral T Cell lymphoma

Question 172

what lymphoma is associated with longstanding coeliac disease?

Answer 172

EATL Enteropathy Associated T cell lymphoma

Question 173

what lymphoma is associated with mycosis fungoides?

Answer 173

Cutaneous T cell lymphoma

Question 174

Affects mainly children/ young adults Histology shows large 'epitheliod' lymphocytes t(2;5) and Alk-1 protein expression Aggressive.

Answer 174

Anaplastic large cell lymphoma

Question 175

Hodgkins Lymphoma - how does it present - associated with which virus - affects which age groups

Answer 175

presents as **asymmetrical painless lymphadenopathy**. most often single node and spreads contiguously to adjacent LNs +/- obstructive/mass effect symptoms **B symptoms** may be present: fever\>38, night sweats, weight loss pain in affected nodes after alcohol assoc w **EBV** bimodal age incidence - ***20-30*** and **\>60**

Question 176

what is the most common subtype of hodgkins lymphoma?

Answer 176

nodular sclerosing 80% good prognosis peak incidence in young women

Question 177

Reed sternberg cell binucleate/ owl eyed cell on a background of lymphocytes and reactive cells LN/ BM biopsy - cells stain with CD15 and CD30

Answer 177

Hodgkins Lymphoma

Question 178

what is the form of non classical hodgkins lymphoma?

Answer 178

nodular lymphocyte predominant hodgkins lymphoma \*expresses CD20 instead of CD15/30 no association w EBV \*\* Reed sternberg cell variant with popcorn shaped nucleus indolent but can transform to high grade B cell lymphoma unlike classical HL

Question 179

Staging of Hodgkins Lymphoma

Answer 179

· I; one group of nodes · II; \>1 group of nodes same side of the diaphragm · III; nodes above and below the diaphragm · IV; extra nodal spread (other organs) · Suffix A if none of below, B if any of below o Fever, night sweats o Unexplained Weight loss \>10% in 6 months \*\*RMB that spleen is considered a LN

Question 180

which of the subtypes of hodgkins lymphoma carry a good prognosis and which carry a poor prognosis?

Answer 180

good: nodular sclerosing mixed cellularity lymphocyte rich poor: lymhocyte depleted

Question 181

treatment of Hodgkins Lymphoma Chemotherapy Radiotherapy

Answer 181

Chemotherapy: ABVD: adriamycin, bleomycin, vinblastine, dacarbazine 2-4 cycles in stage 1/2, 6-8 in stage 3 given at 4 wkly intervals prognosis excellant esp in the young. preserves fertility but can cause long term pulmonary fibrosis, cardiomyopathy Radiotherapy: HL is highly responsive to radiotx usually given at the end of chemo to small area of diseased nodes risk of collateral damage: BrCa, Leukaemia/ MDS, lung/skin Ca

Question 182

what are the chemotherapy drugs used in hodgkins lymphoma tx?

Answer 182

ABVD Adriamycin, Bleomycin, Vinblastine, Dacarbazine/DTIC cycles given at 4 wkly intervals SE: Adriamycin- cardiomyopathy Bleomycin- Pulm fibrosis

Question 183

Tx of Hogdkins Lymphoma in relapse patients

Answer 183

Autologous SCT + Intensive chemo

Question 184

the vessel wall is normal antithrombic, what does it express it on its surface? what factors are produced?

Answer 184

· Expresses anticoagulant molecules o Thrombomodulin o Endothelial protein C receptor o Tissue factor pathway inhibitor o Heparans · Does not express tissue factor · Secretes antiplatelet factors o Prostacyclin, NO

Question 185

what makes the vessel wall prothrombotic?

Answer 185

infection, cancer, vasculitis, trauma anticoagulant molecules downregulated adhesion molecules upregulated TF may be expressed prostacyclin production decreased \*inflammation and malignancy impt stimulants for thrombosis

Question 186

how does stasis promote thrombosis?

Answer 186

accumulation of activated factors promotes platelet adhesion promotes leukocyte adhesion and transmigration hypoxia produces inflammatory effect on endothelium

Question 187

causes of blood stasis?

Answer 187

immobility- surgery, long haul flights, paraparesis compression- tumour, pregnancy viscosity- paraprotein, polycythaemia congenital- vascular abnormalities obese, elderly

Question 188

during surgery, what factors combine to increase risk of clots?

Answer 188

trauma inflammation reduced flow

Question 189

in malignancy, what factors combine to increase risk of clots?

Answer 189

tissue factor on tumour inflammation reduced flow (compressive effects) or poor vasculature architecture

Question 190

in pregnancy, what factors combine to increase risk of clots?

Answer 190

reduced flow (compression effect) decreased protein S increased fVIII, fibrinogen

Question 191

acute treatment of DVT/ PE

Answer 191

LMWH subcut (175 units/kg) and Warfarin or DOACs (directly acting anticoagulants) LMWH subcut works immediately by potentiating Antithrombin III Warfarin has a delayed effect and needs to be used with LMWH as it transiently increases risk of clots by reducing protein C/S levels. DOACs- rivaroxaban (antiXa) and dabigatran (anti IIa)

Question 192

anticoagulant that potentiates antithrombin III - what factors are thus inhibited? - how is this drug given? (oral/im etc) - is monitoring required?

Answer 192

Heparin - thrombin and fIXa/ fXa/ fXIa inactivated - LMWH is given subcut and does not require any monitoring except in late pregnancy and renal failure - Unfractionated heparin is given IV and needs to be monitored (APTT)

Question 193

if necessary, how to monitor LMWH activity?

Answer 193

can use anti-Xa assay to monitor in renal failure patients, extremes of weight or risk

Question 194

antidote for heparin?

Answer 194

protamine sulphate

Question 195

when do you use unfractionated heparin over LMWH?

Answer 195

renal impairment

Question 196

what side effects are associated with heparin tx?

Answer 196

**Bleeding** \***Heparin induced thrombocytopenia** (HIT): low Pl and HIT predisposes to thrombosis (paradoxically) as pl release microparticles that activate thrombin (HITT- heparin induced thrombocytopenia and **thrombosis**) **Osteoporosis** with long term use

Question 197

DOACs e. g. of drugs - what mode of administration - what monitoring

Answer 197

anti Xa e.g. rivaroxaban, apixaban, edoxaban anti IIa e.g. dabigatran oral administration no monitoring required immediated acting also useful long-term (taking over warfarin)

Question 198

Warfarin - how does it work - mode of administration - how to monitor?

Answer 198

inhibits effect by preventing recycling of Vit K, inhibits Vit K dependent carboxylation of factors 2, 7, 9, 10. and proteins C, S and Z onset of action is delayed takes about 2-5 days for factors to fall due to the long half lives of the factors. \* also transiently increases risk of clots initially if given alone monitor PT time. (INR)

Question 199

warfarin overdose tx?

Answer 199

Vit K or factor concentrates

Question 200

Which anticoagulants can you use in pregnancy?

Answer 200

only Heparin is safe Warfarin is teratogenic. DOAC- no data. avoid

Question 201

What is the target INR in those with recurrent DVT/ PE while on warfarin therapy?

Answer 201

3-4 ~3.5

Question 202

what is the target INR of a patient w a mechanical heart valve?

Answer 202

~3 | (2.5-3.5)

Question 203

what is the target INR in 1st episode DVT/ PE, atrial fibrillation, cardiomyopathy, symptomatic inherited thrombophilia, cardioversion?

Answer 203

2-3 ~2.5

Question 204

what is the target INR of a pt with antiphospholipid syndrome and coronary artery thrombosis?

Answer 204

if antiphospholipid syndrome and arterial thrombosis \>3.0 otherwise both conditions aim 2.5 (2.0-3.0)

Question 205

if 1st VTE with known cause, how long would you prescribe oral anticoagulants for?

Answer 205

3 month course

Question 206

e.g. of LMWH

Answer 206

Tinzaparin 4500u Clexane 40mg

Question 207

if Cancer VTE/ 1st VTE unknown cause, how long would you prescribe a course of anticoagulants for?

Answer 207

3-6 months in 1st VTE unknown cause- possibly lifelong

Question 208

if 1st VTE in thrombophilic patient, hwo long would you prescribe anticoagulation for?

Answer 208

3 months, possibly lifelong

Question 209

Bleeding Risk Assessment - Patient risk factors - Procedure risk factors

Answer 209

Patient o Bleeding diathesis (eg haemophilia, VWD) o Platelets \< 100, BP \> 200 syst or 120 dias o Acute CVA in previous month (H’gge or thromb) o Severe liver disease, severe renal disease o Active bleeding o Anticoag or anti-platelet therapy Procedure o Neuro, spinal or eye surgery o Other with high bleeding risk o Lumbar puncture/spinal/epidural in previous 4 hours

Question 210

in Recurrent VTE, how long would you prescribe anticoagulants for?

Answer 210

lifelong keep INR 3.5 if recurrent clots even on warfarin

Question 211

Tx of a DVT/PE - in pt with cancer what oral anticoagulant do you use long term?

Answer 211

LMWH + Warfarin immediately and stop LMWH when INR \>2 for 2 days OR start DOAC continue warfarin/ DOAC for 3-6 months In patients with cancer, continue LMWH not warfarin

Question 212

when might you consider thrombolysis?

Answer 212

only in life threatening PE or limb threatening DVT Risk of haemorrhage ~4% which is a risk not worth it for a simple DVT, but worth it for stroke

Question 213

who is more likely to get a recurrent clot? someone young with no risk factors and no obvious cause or someone post surgery/ on the OCP

Answer 213

the young person with the idiopathic clot! definitely follow up with 6 months anticoagulation, possibly lifelong idiopathic VTE highest risk of recurrence surgical lowest risk of recurrence minor precipitants (cocp, flights, trauma) -\> intermediate risk

Question 214

what anticoagulant is most effective in preventing clots w mechanical heart valves?

Answer 214

warfarin

Question 215

if INR is too high e.g. 5-8 but no bleed, what is the protocol?

Answer 215

withhold few doses reduce maintenance restart when INR \<5

Question 216

if INR too high (5-8) w some minor bleeding, what is the protocol?

Answer 216

stop warfarin. Slow IV vit K restart when INR \<5

Question 217

if INR too high \>8, no bleed/ minor bleed what is the protocol?

Answer 217

stop warfarin oral/ IV vit K check INR daily

Question 218

if INR is high (\>8) and major bleeding what is the protocol?

Answer 218

stop warfarin Give Prothrombin complex concentrate (if unavailable, give FFP) + IV vit K

Question 219

Philadelphia chromosome +ve

Answer 219

CML

Question 220

In true polycythaemia, what happens to the red cell mass and plasma volume? In relative polycythaemia, how is this different?

Answer 220

True polycythaemia: **increased** red cell mass **normal** plasma vol relative polycythaemia: **normal** red cell mass **low** plasma vol - \> appears to be a relative/ pseudopolycythaemia e. g. with alcohol, diuretics, obesity

Question 221

what conditions may see a relative / pseudopolycythaemia?

Answer 221

alcohol obesity diuretics

Question 222

some causes of true secondary polycythaemia

Answer 222

high altitude, cyanotic heart disease, hypoxic lung disease inappropriate- renal cell cancer/ other renal disease, uterine myoma, other tumours

Question 223

in acute leukaemia (ALL and AML) what % of blasts are seen in BM

Answer 223

immature blasts \>20% of BM cells

Question 224

in a myeloproliferative disorder e.g. polycythaemia rubra vera, what processes may be disrupted by mutation?

Answer 224

1. prolong cell survival 2. increase cell proliferation 3. may impair cellular differentiation e. g. creation of novel fusion gene or disruption of proto oncogene

Question 225

headaches, lightheadness, stroke blurred vision plethoric, red nose/ face, gout aquagenic pruritus and peptic ulceration (due to increased histamine release) JAK2 (V167F) mutation O/E: splenomegaly, plethora, thrombosis Raised Hb, HCT, + possibly increased WCC/ Platelets

Answer 225

Polycythaemia rubra vera symptoms of hyperviscosity and increased histamine release splenomegaly erythromelalgia (red painful extremities) retinal vein engorgement Gout due to increased red cell turnover

Question 226

IX of suspected polycythaemia rubra vera where Hb high/ Hct High etc

Answer 226

JAK2 V617 mutation - look for Low serum EPO Bone marrow aspiration and trephine biopsy

Question 227

tx of polycythaemia rubra vera

Answer 227

reduce hyperviscosity venesection cytoreductive therapy for maintenance: hydroxycarbamide reduce risk of thrombosis: aspirin and keep Pl below 400 x10⁹/L

Question 228

definition of essential thrombocythaemia

Answer 228

chronic myeloproliferative disease involving the megakaryocyte lineage megakaryocytes dominate the BM sustained thrombocytosis \>600 x10⁹/L

Question 229

what condition may ruxolotinib JAK2 inhibitor be used in?

Answer 229

myelofibrosis

Question 230

venous and arterial thrombosis e.g. stroke, MI, PE Erythromelalgia - red painful burning sensation in the extremities mucous membrane / cutaneous bleeding headaches, dizziness, visual disturbances, modest splenomegaly Pl count high, no other cell lines affected. what condition?

Answer 230

Essential thrombocythaemia - incidental finding in 50% 50% associated with JAK2 Blood film shows large platelets and megakaryocyte fragments Increased BM megakaryocytes

Question 231

Tx of essential thrombocythaemia?

Answer 231

Aspirin to prevent thrombosis Anagrelide: to inhibt maturation of platelets from megakaryocytes Hydroxycarbamide: antimetabolite

Question 232

a myeloproliferative disease with proliferation of mainly megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haematopoiesis usually in elderly may be secondary to other haematological disease: e.g. progression from PV or ET

Answer 232

myelofibrosis

Question 233

Blood film- tear drop poikilocytes (dacrocytes) and leukoerythroblasts Dry tap on BM biopsy extramedullary haemopoiesis - massive splenomegaly (budd chiari syndrome may present), hepatomegaly pancytopenia: anaemia, thrombocytopenia, neutropenia hypermetabolic state: weight loss, fatigue, night sweats, hyperuricaemia

Answer 233

myelofibrosis

Question 234

in myelofibrosis - what is found on BM aspirate - treatment - prognosis

Answer 234

fibrosis of BM, deposition of collagen and later osteosclerosis Tx: blood transfusions for anaemia pl transfusion often ineffective splenectomy for symptomatic relief hydroxycarbamide: cytoreductive therapy Ruxolotinib JAK2 inhibitor SCT in young patients may be curative prognosis: median 3-5 yrs bad prognostic signs: sever anaemia, thrombocytopenia, massive splenomegaly

Question 235

features of anaemia/ bleeding/ brusing FLAWS, gout O/E: massive splenomegaly +/- hepatomegaly FBC: Hb/ Pl usually well preserved. Massive leucocytosis. 50-200 x 10⁹/ L Normal (4-11) Blood film: neutrophilia + basophilia + myelocytes (mature myeloid cells) Philadelphia chromosome +ve what condition?

Answer 235

CML

Question 236

Ix in CML?

Answer 236

PCR for **BCR-ABL** (philadelphia chr) fusion gene Ph Chr +ve in 80% t(9;22) WCC, FBC Blood film: neutrophils, myelocytes, basophilia Can monitor disease and treatment response with FBC, BCR-ABL:ABL ratio

Question 237

chronic phase vs accelerated phase vs blast phase of CML? no of blasts in BM/blood

Answer 237

chronic (80% of pts): \<5% blasts indolent Accelerated: 10%-19% blasts increasing manifestations e.g. splenomegaly Blast crisis: \>20% blasts median survival 3-6 months resembles acute leukaemia

Question 238

t(9;22)

Answer 238

produces philadelphia chrosome (BCR-ABL gene) seen in CML expresses a fusion oncogene with tyrosine kinase activity can be detected using FISH

Question 239

how to monitor disease and response to therapy in CML

Answer 239

FBC and WCC count cytogenetics and detection of Ph chr - reduction in % of Ph Chr expressed RT-PCR of BCR-ABL fusion transcript. can calculate BCR-ABL: ABL ratio successful therapy means this will drop e.g. complete response: 0% Ph +ve partial response 1-35% Ph +ve BCR-ABL transcripts reduce from 100% to the best - 0.001%

Question 240

a heterogenous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells -\> functionally defective cells + numerical reduction

Answer 240

Myelodysplastic Syndrome

Question 241

Treatment of CML

Answer 241

**Imatinib**\* a BCR-ABL tyrosine kinase inhibitor or if resistant -2nd line: Dasatinib/ Nilotinib young patients- possible allogeneic SCT

Question 242

typically seen in elderly Hypercellular BM - 5-19% blasts (\<5% is normal. \>20% is acute leukaemia) BM failure and cytopenias- infection, bleeding, fatigue Blood film: Pseudo-Pelger-Huet anomaly, hypogranulation of neutrophils, micromegakaryocytes, hypolobulated nuclei, ringed sideroblasts (abnormally high iron accumulation - seen w prussian blue stain) may also see myeloblasts w Auer rods

Answer 242

Myelodysplastic syndrome

Question 243

megakaryocytes with hypolobulated nuclei and \<5% blasts blood features: anaemia, normal or increased pl what subtype of MDS?

Answer 243

MDS w 5q deletion responds v well to treatment

Question 244

BM shows 10-19% blasts or Auer rods blood features- cytopenias or 10-19% blasts or Auer rods what subtype of MDS?

Answer 244

refractory anaemia with excess blasts II (RAEB II)

Question 245

bone marrow shows 5-9% blasts Blood: cytopenias, \<5% blasts, no auer rods what subtype of MDS?

Answer 245

Refractory Anaemia with Excess Blasts (RAEB I)

Question 246

Bone marrow shows erythroid dysplasia with \>15% ringed sideroblasts blood features: anaemia, no blasts what subtype of MDS?

Answer 246

Refractory anaemia with ringed sideroblasts

Question 247

Bone marrow shows dysplasia in \>10% cells in 2 or more cell lines and \>15% ringed sideroblasts blood: cytopenia in 2 or more cell lines what subtype of MDS?

Answer 247

refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD + RS)

Question 248

Bone marrow shows erythroid dysplasia w \<5% blasts blood: anaemia, no blasts what subtype of MDS?

Answer 248

Refractory Anaemia

Question 249

Bone marrow shows dysplasia in \>10% cells in 2 or more cell lines Bloods: cytopenia in 2 or more cell lines what subtype of MDS?

Answer 249

refractory cytopenia with Multilineage dysplasia RCMD

Question 250

myelodysplatic syndrome complications

Answer 250

development of AML (AML from MDS has extremely poor prognosis) 1/3 die from infection, 1/3 die from bleeding and 1/3 from acute leukaemia

Question 251

Treatment of Myelodysplastic syndrome

Answer 251

Allogeneic SCT Intensive chemotherapy- AML type regimen most will just have: supportive care: transfusions, ABx, Growth factors (EPO, G-CSF) given by subcut injection biological modifiers- immunosuppressive therapy, azacytidine, lenalidomide Oral chemo: hydroxyurea low dose chemo- low dose cytarabine

Question 252

BM failure: Anaemia/ Leucopenia/ Thrombocytopenia Blood- anaemia or even pancytopenia trephine biopsy shows a hypocellular BM (\<25% cellularity)

Answer 252

aplastic anaemia

Question 253

Management of Aplastic Anameia

Answer 253

seek a cause e.g. drug/ occupational exposure history supportive- blood/pl transfusions (leucodepleted, CMV neg, irradiated blood), ABx, iron chelation therapy due to transfusion (when transferrin \>1000) drugs to promote marrow recovery- growth factors and oxymetholone/ Danazol (androgen) SCT - for younger pts w donor (\<35) immunosuppressants e.g. anti lymphocyte globulin and ciclosporin for \>50 yr

Question 254

what are some secondary causes of aplastic anaemia?

Answer 254

malignant infiltration of BM radiation Drugs e.g. carbimazole, chloramphenicol, carbamazepine viruses e.g. Parvovirus B19 SLE

Question 255

AA is closely linked to development of which conditions in the future?

Answer 255

MDS, leukaemia paroxysmal nocturnal haemoglobinuria solid tumours

Question 256

Fanconi anaemia - inheritance pattern - presentation

Answer 256

most common form of inherited AA most commonly autosomal recessive causes **Pancytopenia** presents at 5-10 yrs with skeletal abnormalities (thumbs), renal malformations, microophthalmia, short stature, skin pigmentation (cafe au lait spots/ hypopigmentation)

Question 257

fanconi anaemia increases the risk of progression to which conditions?

Answer 257

30% progress to MDS and 10% to AML treatment= supportive + androgens can transiently improve counts but consider SCT

Question 258

Classical triad of abnormal skin pigmentation, nail dystrophy, oral leukoplakia + BM failure, cancer predisposition and somatic abnormalities

Answer 258

dyskeratosis congenita

Question 259

Diamond-Blackfan syndrome

Answer 259

pure red cell aplasia normal WCC and platelets presents at 1yr/ neonatal dysmorphology

Question 260

what is the most common inheritance pattern of dyskeratosis congenita?

Answer 260

x-linked recessive. Classical triad of abnormal skin pigmentation, nail dystrophy, oral leukoplakia + BM failure, cancer predisposition and somatic abnormalities

Question 261

Schwachman-Diamond syndrome

Answer 261

primarily neutrophilia skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature AML risk

Question 262

80% of cases diagnosed on routine bloods if symptomatic: symmetrical painless lymphadenopathy BM failure- anaemia, infections, bleeding weight loss, low grade fever, night swetas splenomegaly & hepatomegaly assoc with AIHA, ITP may undergo Richter's transformation WCC: high WCC with lymphocytosis

Answer 262

CLL \***smear CLLs** BM- lymphocytic replacement, anaemia, thrombocytopenia Low serum Ig

Question 263

CLL - which prognostic markers are good and which are bad LDH CD38 11q23 deletion Low ZAP-70 Hypermutated Ig gene 13q14 deletion

Answer 263

Bad: High LDH (marker of tumour turnover) CD38 +ve 11q23 deletion Good: Low ZAP-70 Hypermutated Ig gene 13q14 deletion

Question 264

Binet Staging A, B, C via CT/ PET scan

Answer 264

_Stage A:_ High WBC \<3 groups of enlarged LNs usually no tx required _Stage B:_ \>3 groups of enlarged LNs _Stage C:_ anaemia or thrombocytopenia

Question 265

cell markers on normal B cell vs B-CLL cells CD5 CD19

Answer 265

Normal: CD5- CD19+ B-CLL: CD5+ CD19-

Question 266

treatment of CLL

Answer 266

many patients undergo watchful waiting if asymptomatic with slowly progressive disease 1st line: alemtuzumab (depletes lymphocytes) supportive: abx, vaccination, e.g. aciclovir, PCP prophylaxis, IVIG, pneumovax young patients: allogeneic SCT Autoimmune phenomena: 1st line steroids. 2nd line Rituximab

Question 267

Classify these conditions into their groups of very aggressive/ aggressive/ indolent Burkitt's Lymphoma Mantle Cell Lymphoma Follicular Small lymphocytic/ CLL MALT Diffuse Large B cell ALL

Answer 267

Very aggressive: Burkitts ALL Aggressive: Diffuse Large B cell Mantle Cell Indolent Small lymphocytic/CLL Follicular MALT the indolent ones are more incurable whereas the aggressive ones are most curable

Question 268

Treatment for DLBCL

Answer 268

6-8 cycles of Rituximab-CHOP aim of therapy is curative if relapse-\> 2nd line tx: autologous SCT

Question 269

what drugs does R-CHOP consist of?

Answer 269

Rituximab (anti CD20) Cyclophosphamide Adriamycin Oncovin aka Vincristine Prednisolone

Question 270

tx for follicular lymphoma

Answer 270

Watch and wait. only treat if indicated e.g recurrent infections, nodes compressing bowel/ureter may require 2-3 chemotherapy schedules over the 12-15 yr period each chemotherapy becomes less and less effective 1st line: R-CVP

Question 271

Tx of Gastric MALToma

Answer 271

eradication of H pylori: omeprazole/ clarithromycin/ amoxicillin repeat breath test at 2months and endoscopy every 6 months for 2 yrs then annually if eradication therapy fails then chemo

Question 272

which surface protein do both CD4+ and CD8+ T cells have?

Answer 272

CD3

Question 273

what may undergo richter transformation to DLBCL?

Answer 273

CLL hairy cell leukaemia

Question 274

CLL prophylaxis and treatment of infections

Answer 274

Aciclovir PCP prophylaxis for those receiving fludarabine or alemtuzumab IVIG for those w hypogammaglobulinaemia and recurrent bacterial infections Immunisation against pneumococcus and seasonal flu

Question 275

CLL autoimmune phenomena e.g. AIHA mx?

Answer 275

1st line steroids 2nd line rituximab

Question 276

why does pregnancy cause a mild anaemia physiologically?

Answer 276

red cell mass increases but plasma volume rises further overall net dilution

Question 277

normal blood changes in pregnancy

Answer 277

mild anaemia macrocytosis neutrophilia thrombocytopenia

Question 278

Pregnancy demands increased requirements of? -may need supplementation

Answer 278

Iron requirement Recommend to take 60mg Fe daily during pregnancy if fe deficient Folate requirement (400mcg / 5mg in pregnancy) - to reduce risk of neural tube defects supplementation before conception til 12 wks gestation

Question 279

Normal values of Pl in pregnancy? - why is pl count impt

Answer 279

175-200 normal if platelets between 70-80, have to assess safety for epidural anaesthesia. \>70 required for epidural \>50 sufficient for delivery

Question 280

causes of low Pl in pregnancy

Answer 280

physiological: gestational (normal for a drop of 10%) preeclampsia (proportional to pl count) immune thrombocytopenic purpura (may require IVIG) TTP, MAHA

Question 281

a hypercoagulable state in pregnancy is seen due to?

Answer 281

fVIII and vWF increase 3-5 fold fibrinogen increases 2 fold fVII invreases 0.5 fold Protein S falls -\> 7, 8, vwf and fibrinogen increase and anticoagulant protein s falls allows rapid control of bleeding from placental site at time of delivery net effect: a procoagulant state which increases rate of thrombosis. increased thrombin generation, increased fibrin formation, decreased fibrinolysis

Question 282

Prevention of thrombosis in pregnancy:

Answer 282

women with risk factors (age, weight) should receive prophylactic heparin + TED stockings either throughout pregnancy or in the post partum period mobilise early, maintain hydration

Question 283

Tx of DVT/ PE in pregnancy

Answer 283

LMWH - will not cross placenta monitor antiXa stop for labour or planner delivery esp for epidural. Epidural: wait for 24h after tx dose and 12h after prophylactic dose

Question 284

Tx of antiphospholipid syndrome in pregnancy·

Answer 284

Recurrent miscarriage + persistent Lupus anticoagulant (LA)/ anticardiolipin Abs (ACL) \>3 consecutive miscarriages before 10 weeks of gestation OR One or more morphologically normal fetal losses after the 10th week of gestation OR one or more preterm births before the 34th week of gestation owing to placental disease. **Treatment of aspirin and heparin** increase chances of live births

Question 285

sudden onset shivers, vomiting, shock, DIC 86% mortality presumed due to tissue factor in amniotic fluid

Answer 285

amniotic fluid embolism

Question 286

high HbA₂ in blood (\>3.5%) suggests?

Answer 286

Beta thal

Question 287

Process of Autologous SCT:

Answer 287

* Growth factor injected into patient * Collect stem cells and freeze * High dose chemo given to pt * Thaw and reinfuse pt with their stem cells To allow higher dose chemo suitable for ALL, CLL, myeloma, lymphoma, solid tumours

Question 288

process for allogeneic transplant:

Answer 288

* high dose chemo +/- radio to patient until BM is fried * donor donates BM stem cells to complete replace recipients BM w healthy cells suitable for ALL/AML, CML/CLL, myeloma, BM failure, lymphoma, congenital immune deficiencies

Question 289

Which chromosome is HLA gene found on?

Answer 289

chr 6

Question 290

what cell surface marker is expressed on stem cells?

Answer 290

CD34

Question 291

what affects outcome of SCT? e.g. age/ gender/ disease phase

Answer 291

age \>40 late in disease phase female into male recipient \>1 yr to BMT non sibling donor

Question 292

Paediatric Haemotology: what differences are there?

Answer 292

low [Hb] higher lymphocytes smaller MCV

Question 293

Neonatal Blood count: how is it different from that of an adult?

Answer 293

WCC, neutrophil and lymphocyte counts are high [Hb] and MCV high Neonates have higher % HbF so disorders of beta globin genes are much less likely to be manifest Enzyme levels in red cell also differ, e.g. G6PD concentration is about 50% higher than in adults

Question 294

causes of polycythaemia in a neonate:

Answer 294

twin to twin transfusion syndrome fetal hypoxia Placental insufficiency

Question 295

Potential causes of anaemia in the neonate:

Answer 295

twin to twin transfusion fetal to maternal transfusion parvovirus b19 haemorrhage from cord/placenta anticoagulant drugs

Question 296

Congenital leukaemia is particularly common in ?

Answer 296

Down's syndrome The leukaemia is myeloid with major involvement of the megakaryocyte lineage The most remarkable feature is that it usually remits spontaneously and relapse 1-2 years later in only about a quarter of infants

Question 297

what globin chains make up HbF

Answer 297

a₂ gamma₂

Question 298

what globin chains make up HbA₂?

Answer 298

2 alpha and 2 delta chains

Question 299

what globin chains make up HbA?

Answer 299

2 alpha + 2 beta chains

Question 300

bleeding following circumcision haemarthroses deep bruises, prolonged bleeding after surgery/ trauma prolonged APTT normal PT what conditions? what ix? inheritance pattern

Answer 300

Haemophilia A or B Ix: fVIII/ fIX assay if low fVIII-\> Haemophilia A if low fIX -\> Haemophilia B both are X-linked recessive conditions may have had umbilical cord bleeding, haematoma during vaccinations

Question 301

Mx of Haemophilia A/B

Answer 301

Counselling of family Treatment of bleeding episodes fVIII/ fIX concentrates as replacement life-long in haemophilia A: desmopressin (which increases vwf release of fVIII as vwf is a fVIII carrier) Avoid NSAIDs and IM injections

Question 302

mucosal bleeding bruises post traumatic bleeding increased APTT, increased bleeding time, decreased fVIII, decreased vWF + decreased ristocetein cofactor activity normal INR and pl count what condition?

Answer 302

von Willebrand disease vWF carries fVIII in circulation. so defective/ reduced vWF also causes reduced fVIII. mostly auto dominant

Question 303

mx of von willebrand disease?

Answer 303

desmopressin VWF and fVIII concentrates

Question 304

AML - age of incidence - mutations seen - pathognomonic features

Answer 304

bimodal incidence: peak in under 2s and in 65-70yos many mutations assoc with AML t(5;8), inv(16), t(8;21), trisomy 8, trisomy 21 \>20% myeloblasts on BM + **Auer Rods**

Question 305

Risk factors for developing ALL/AML

Answer 305

ionising radiation- radiotx chemotx benzene MDS/ myeloproliferative disorders Downs: signficantly increased risk of AML

Question 306

t(15;17) excess of abnormal promyelocytes DIC PML-RARA fusion protein

Answer 306

Acute promyelocytic leukaemia

Question 307

how to differentiate AML and ALL

Answer 307

cytological features on histology (AML has fine granules & more cytoplasm than ALL) cytochemistry (Myeloperoxidase +ve, Sudan Black B +ve, Non specific esterase +ve in AML) Immunophenotyping: ALL: CD19 (B cells), CD3 (T cells), CD34 (stem cells) AML: CD34 (stem cells), MPO (Myeloid cells), CD13/ CD33

Question 308

AML - typical features - more specific features - Blood film features

Answer 308

BM failure- effects of pancytopenia Splenomegaly, hepatomegaly Gum infiltration if monoblasts/ monocytic Skin infiltration/ CNS involvement + hypoK Blood film: circulating blasts with granules. auer rods. if unclear- immunophenotyping

Question 309

treatment of AML

Answer 309

Supportive care: blood products, abx, FFP/Cryoprecipitate if DIC, allopurinol, fluid and electrolytes to prevent tumour lysis syndrome Chemotherapy Consider Allo SCT in young Specific for acute promyelocytic leukaemia: ATRA

Question 310

ALL - peak age incidence - clinical features

Answer 310

peak incidence in childhood BM failure - pancytopenia hepatosplenomegaly **lymphadenopathy** **thymic enlargement** **testicular enlargement** **bone pain**

Question 311

ALL Ix

Answer 311

· Blood count and film, bone marrow aspirate · Immunophenotyping – matters as T (15%) and B-lineage (85%) ALL may be treated differently · Cytogenetic/molecular genetic analysis - Ph positive need imatinib, treatment must be tailored to the prognosis · Blood group, LFTs, creatinine, electrolytes, calcium, phosphate, uric acid, coagulation screen

Question 312

tumour lysis syndrome

Answer 312

complication of treating cancer where large amts of tumour cells are lysed at the same time occurs most commonly after tx of lymphomas and leukaemias high K, high PO4, high Uric acid, high blood urea nitrogen may cause acute kidney failure, seizures, cardiac arrhythmias and death

Question 313

Tx of ALL

Answer 313

· Specific therapy – systemic or CNS-directed chemotherapy · Supportive care – blood products, antibiotics, general medical care, prophylaxis for Pneumocystis jiroveciiinfection · Hyperuricaemia: hydration, urine alkalinization and allopurinol or rasburicase · Hyperphosphataemia; Al(OH)3, calcium · Hyperkalemia: fluids, diuretics · Extreme leukocytosis (WBC \> 200 × 109/l): leukapheresis, sometimes haemodialysis

Question 314

when to transfuse red cells:

Answer 314

major blood loss: \>30% blood vol lost peri op, crit care: Hb\<70g/L post chemo: Hb \<80g/L symptomatic anaemia- IHD, breathless, ECG changes Give ABO/D compatible, O- in emergency transfuse 1 unit RBC over 2-3h 1 unit should increase Hb by 10g/L in a 70/80kg patient

Question 315

In Blood transfusions some special requirements

Answer 315

· **CMV -ve blood** - only required for intra-uterine and neonatal transfusions (new guidance 2012). Also for elective transfusion in pregnant women (baby in-utero is exposed to maternal transfusion) **Irradiated blood** - required for highly immunosupressed patients, who cannot destroy incoming donor lymphocytes: which can cause (fatal) transfusion associated graft versus host disease (TA-GvHD) · **Washed** - red cells and platelets are only given to patients who have severe allergic reactions to some donors’ plasma proteins

Question 316

indications for platelet transfusion:

Answer 316

prevent bleeding (surgery): Pl\< 50 or if critical site like CNS, eye: \<100 prevent bleeding post chemo: pl\<10 (\<20 if sepsis) consumptive disorders e.g. DIC transfuse 1 u pl over 20-30 min One unit of platelets is an adult treatment dose: usually raises platelet count by 30-40 x109/L Platelet transfusion is contraindicated in heparin-induced thrombocytopenia (HIT) and TTP

Question 317

FFP - indications

Answer 317

FFP contains all clotting factors DIC with bleeding Liver disease + risk: PT ratio \>1.5 x normal Blood loss \>150ml/min

Question 318

pt just had a blood transfusion, rise in temperature (**low** fever), chills, rigors. what is this? how to manage?

Answer 318

febrile non-haemolytic transfusion reaction occurs during/soon after transfusion WBC can release cytokines during storage- rarer now that blood is leucodepleted mx: stop or slow transfusion, may need to treat with paracetamol

Question 319

pt just had a transfusion, common especially w plasma mild, urticarial itchy rash +/- wheeze what is the cause? mx?

Answer 319

allergic transfusion reaction allergy to a plasma protein from donor more common in patients with history of atopy/ allergies usually have to stop or slow transfusion mx: IV antihistamines to treat

Question 320

pt has just had transfusion 1-2h post transfusion restless, abdo/loin pain, vomiting, fever, collapse, haemoglobinuria (dark urine) signs: BP drops, HR goes up, temp high what has happened?

Answer 320

ABO incompatibility - most severe: A blood group into group O A/ B IgM antibodies are naturally occuring in plasma potentially fatal intravascular haemolysis take samples for FBC, biochemistry, coagulation, repeat cross match and direct antiglobulin test

Question 321

pt has had a blood transfusion high fevers, rigors, vomiting, flushing, collapse hypotension, high HR (shock) and **High fever** what has happened?

Answer 321

Bacterial contamination presents very similarly to wrong ABO blood bacterial growth can cause endotoxin production which causes immediate collapse Platelets \> red cells \> frozen components in terms of (storage temp)

Question 322

prevention of bacterial contamination

Answer 322

· Donor questioning + arm cleaning + diversion of first 20mL into a pouch (used for testing) · Red cells: Store always in controlled fridge 4⁰C; shelf-life 35 days. If out for \>½ hour, need to go back in fridge for 6 hours. Complete transfusion of blood within 4.5h of leaving fridge i.e. transfuse over 4hrs max · Platelets: stored at 22⁰C; shelf-life 7 days (as now screened for bacteria before release) · All components: look for abnormalities e.g. clumps of discoloured debris; brown plasma etc

Question 323

pt has had a blood transfusion shock- drop in BP and increased HR, very breathless with wheeze + laryngeal and facial oedema what is happening?

Answer 323

anaphylaxis severe, life thrreatening reaction soon after start of transfusion IgE antibodies in pt cause mast cell release of granules & vasoactive substances. Most allergic reactions are not severe, but some can be e.g. in **IgA deficiency**

Question 324

pt has had a transfusion acute SOB, dry cough, fever normal JVP, low O2 sats, high HR, high BP CXR shows bilateral pulmonary infiltrates during/ within 6h of transfusion what happened?

Answer 324

TRALI transfusion related acute lung injury acute non-cardiogenic pulmonary oedema that occurs within 6h following a blood transfusion. anti-WBC abs in donor interact with corresponding Ag on patient's WBCs-\> aggregates of WBCs get stuck in pulmonary capillaries -\> release neutrophil proteolytic enzymes and toxic O2 metabolites that cause lung damage

Question 325

fluid overload following blood transfusion pulmonary oedema SOB, hypoxia, high HR, high BP CXR shows fluid overload/ cardiac failure what is happening?

Answer 325

transfusion associated circulatory overload TACO esp in those w cardiac failure, renal impairment, hypoalbuminaemia

Question 326

blood transfusion over 24 h ago usually occurs 5-10 days after jaundice, haemoglobinuria high Br, low Hb, high reticulocytes what is happening?

Answer 326

Delayed haemolytic transfusion reaction extravascular haemolysis that takes 5-10 days Test U&Es as can cause renal failure repeat G&S for new antibody?

Question 327

History of transplant/ transfusion severe diarrhoea, liver failure, skin dequamation, bone marrow failure -\> death weeks to months post transfusion what has happened?

Answer 327

Transplant/ transfusion assoc GVHD rare but always fatal Donors blood contains some lymphocytes (normally the host's immune system recognises these as foreign and destroys. them) In susceptible patients - lymphocytes not destroyed lymphocytes recognise patient's tissue HLA antigens as foreign- attack gut, liver, skin, bone marrow Prevent: irradiate blood components for very immunosuppressed pts who cannot destroy incoming donor lymphocytes

Question 328

transfusion of blood or platelets purpura appears 7-10 days after resolves in 1-4 wks purpura = pin prick red/ purple blood spots due to v low platelets \<20 x 10⁹ what is happening?

Answer 328

Post transfusion Purpura · Affects HPA -1a negative patients - previously immunised by pregnancy or transfusion (**anti-HPA-1a antibody**) treatment: infusion of IVIG

Question 329

in haemolytic disease of the fetus/ newborn, what antibody crosses the placenta?

Answer 329

Anti-D IgG antibodies cross the placenta and bind and destry fetal red cells -\> fetal anaemia, hydrops fetalis and neonatal jaundice/ kernicterus

Question 330

when are Rh-ve women screened for anti-D antibodies?

Answer 330

at booking 12 wks and 28 wks

Question 331

Mx of mother with anti-D antibodies and RhD+ fetus

Answer 331

· Monitor fetus for anaemia – MCA Doppler US · Deliver baby early, as HDN gets a lot worse in last few weeks of pregnancy If necessary, intra-uterine transfusion can be given to fetus in specialised centres, highly skilled - needle in umbilical vein · At delivery - monitor baby’s Hb and bilirubin for several days as HDN can get worse for few days · Can give exchange transfusion to baby if needed to decrease bilirubin and increase Hb; plus phototherapy to drop bilirubin

Question 332

prevention of Haemolytic Disease of Fetus/ Newborn

Answer 332

Anti-D Ig prophylaxis RhD +ve (fetal) red cells get coated with anti-D Ig which are removed by the mother’s reticuloendothelial system (spleen) before they can sensitise the mother to produce anti-D Abs · To be effective - must give anti-D injection within 72 hours of the ‘sensitising event’ e.g. spontaneous miscarriages if surgical evacuation needed, amniocntesis and CVS, abdo trauma, external cephalic version, stillbirth or intrauterine death

Question 333

what dose of anti-D to give at what phase?

Answer 333

125iu of Anti-D covers 1 ml of fetal blood at least 250iu for events before wk 20 and at least 500iu for events any time after wk 20 larger does needed for larger bleed - do **Kleihauer test** to determine dose needed so 500iu - up to 4ml, 1250iu - 10ml, 1500iu- 12ml

Question 334

when is routine antenatal anti-D prophylaxis given?

Answer 334

1500iu anti-D at 28-30 wks or 2 doses (1 at 28 wk and another at wk 34) within 72h after delivery

Question 335

what are some other antibodies that can cause haemolytic disease of newborn?

Answer 335

anti-c, anti-kell antibodies anti-A and anti-B

Question 336

where is basophilic stippling seen?

Answer 336

beta thal trait lead poisoning alcoholism sideroblastic anaemia megaloblastic anaemia myelodysplasia

Question 337

what conditions might show target cells/ codocytes on blood film

Answer 337

iron deficiency anaemia thalassaemia hyposplenism liver disease

Question 338

Bone marrow shows \<10% clonal plasma cells. IgG/IgA \<30g/l no symptoms/ no CRAB

Answer 338

MGUS monoclonal gammopathy of undertermined significance no treatment needed small transformation rate (1-2% risk progression to MM)

Question 339

features of multiple myeloma

Answer 339

CRAB hypercalcaemia - stones, bones, groans, moans renal impairment anaemia bone pain, osteolytic lesions, fractures, osteoporosis

Question 340

Ix of Multiple myeloma

Answer 340

serum Ca, high ESR Xray/ MRI bone pain areas blood film shows Rouleaux formation Urine: bence-jones protein serum protein electrophoresis: dense narrow band BM aspirate: \>10% plasma cells

Question 341

what % plasma cells is found in a normal BM

Answer 341

5%

Question 342

what is the first investigation you want to do when you suspect Multiple myeloma?

Answer 342

serum protein electrophoresis - paraprotein detected

Question 343

what is seen on BM aspirate of someone with MM?

Answer 343

MM can have 40-90% plasma cells in their BM may look like normal plasma cells clumped chromatin, rare nucleoli, immature plasmablasts, less abundant cytoplasm

Question 344

what cell surface markers are found on multiple myeloma cells

Answer 344

CD38, CD138 negative for CD19, 20 (usually expressed on B cells),

Question 345

myeloma bone disease: possible complications

Answer 345

80-90% have lytic lesions pathological fractures spinal cord compression leading to paralysis hypercalcaemia bone pain -\> affecting QOL, independence, mobility too many osteoclasts (from increased IL6) and not enough active osteoblasts

Question 346

what investigations for myeloma bone disease

Answer 346

X ray - for lytic lesions MRI- High sensitivity for marrow infiltration, response monitoring possible, expensive & limited availability CT – full body CT is the standard used in Imperial to diagnose as it detects very small lesions (high sensitivity). Good for radiotherapy planning but higher radiation dose PET - detects active disease

Question 347

why does multiple myeloma cause renal failure?

Answer 347

free light chains cause injury to kidneys - active inflammatory mediators in the proximal tubule epithelium -\> leads to amyloidosis (AL chains) cast nephropathy

Question 348

treatment of multiple myeloma

Answer 348

supportive for CRAB symptoms including bisphosphonates Auto-SCT - curative, best for younger patients steroids Classical cytostatic drugs (relatively low dose) eg. melphalan Proteasome inhibitors – prevent misfolded proteins from being degraded, which accumulates in myeloma cells (esp effective as myeloma produces a lot of proteins) e.g. bortezomib IMIDs – thalidomide, lenalidomide, pomalidomide (also used in MDS). Reduces cell turnover by affecting transcription factor relevant for plasma cells

Question 349

what is the normal life span of platelets?

Answer 349

10 days

Question 350

what do platelets release to trigger platelet activation?

Answer 350

release of ADP and thromboxane

Question 351

what is the common progenitor of thromboxane A2 and prostacyclin PgI2?

Answer 351

Cyclic endoperoxidases This is converted into thromboxane A2 via thromboxane synthetase and to prostacyclin PgI2 via prostacyclin synthase Arachidonic acid is converted to cyclic endoperoxidases via cyclo oxygenase

Question 352

what does tissue factor pathway inhibitor inhibit?

Answer 352

TF-fVIIa complex

Question 353

what is factor V leiden?

Answer 353

factor V leiden cannot be cleaved by activated protein C

Question 354

Bone marrow shows \>10% clonal plasma cells IgG/IgA \>30g/L no CRAB symptoms, no organ damage no treatment needed

Answer 354

smouldering MM

Question 355

what is Clopidogrel?

Answer 355

an antiplatelet an ADP inhibitor irreversible non competitive inhibitor inhibits ADP binding to its Platelet membrane receptors -\> inhibiting activation of gpIIb/IIIa

Question 356

how does aspirin work as an antiplatelet?

Answer 356

inhibits cyclo oxygenase enzyme and affects the thromboxane A₂ pathway it is the most widely used antiplatelet treatment

Question 357

how does dipyridamole work?

Answer 357

antiplatelet inhibits platelet aggregation by blocking the reuptake of adenosine formed from precursors released by RBC after microtrauma

Question 358

christmas disease aka?

Answer 358

haemophilia B

Question 359

DIC - what happens?

Answer 359

systemic activation of coagulation and fibrinolysis caused by sepsis, obstetric complications, reaction to toxin, etc - \> intravascular deposition of fibrin -\> thrombosis of small and midsize vessels with organ failure - \> depletion of platelets and coagulation factors -\> bleeding

Question 360

DIC - blood test results

Answer 360

APTT, PT, TT increased fibrinogen decreased increased fibrin degradation products low platelets and increased shistocytes (MAHA) tx of underlying disorder platelet transfusion, FFP

Question 361

how does liver disease affect clotting factors?

Answer 361

decreased synthesis of 2, 5, 7, 9, 10, 11 and fibrinogen decreased absorption of Vit K abnormalities of pl function tx: vit K, FFP, cryoprecipitate

Question 362

sideroblastic anaemia - diagnosis - treatment

Answer 362

sideroblastic anaemia - ineffective erythropoiesis -\> iron loading causing haemosiderosis (endocrine, liver, cardiac damage) diagnosis: ring sideroblasts seen in marrow tx: remove the cause (e.g. MDS, following chemo, alcohol excess, lead excess), and Pyridoxine (Vit B6 promotes RBC production)

Question 363

what are sideroblasts?

Answer 363

sideroblasts are atypical, abnormal nucleated erythoblasts with granules of iron accumulated in the mitochondria surrounding the nucleus. ring sideroblasts: iron laden mitochondria form a ring around the nucleus the body has iron available but cannot incorporate it into Hb. peripheral blood smear: basophilic stippling, pappenheimer bodies (cytoplasmic granules of iron)

Question 364

Answer 364

stomatocytes RBCs that have a fish mouth appearance or 'smiling face' appearance. usually seen in alcoholics, liver disease, and hereditary stomatocytosis.

Question 365

what conditions are associated w stomatocytes?

Answer 365

alcoholics, liver disease, and hereditary stomatocytosis.

Question 366

Bernard- soulier syndrome

Answer 366

mutation of glycoprotein 1 b bleeding disorder

Question 367

Glanzmanns thrombasthenia

Answer 367

mutation of gpIIb/IIIa -\> blood coagulation

Question 368

what causes the most severe ABO incompatible blood transfusion? what blood group to what?

Answer 368

Group A into goup O recipient

Question 369

Delayed haemolytic transfusion reactions most frequent antibodies against?

Answer 369

Kidd (Jk) and Rh systems these occur when pts are sensitised from previous transfusions/ pregnancies, and therefore have antibodies against red cell antigens which are not picked up by routine blood bank screening if they are below detectable limits.

Question 370

blood film features suggesting hyposplenism

Answer 370

howell-jolly bodies target cells acanthocytes

Question 371

TIBC / transferrin saturation levels in IDA

Answer 371

TIBC / Transferrin High Transferrin saturation LOW low Fe, low ferritin

Question 372

TIBC/ transferrin saturation lvls in haemochromatosis

Answer 372

TIBC/ transferrin LOW transferrin saturation high Iron high, ferritin high

Question 373

TIBC/ transferrin saturation of anaemia of chronic disease

Answer 373

TIBC/ transferrin low Transferrin saturation low Fe low Ferritin high

Question 374

chronic haemolysis TIBC/ transferrin saturation

Answer 374

transferrin/ TIBC low Transferrin saturation high Iron High Ferritin High

Question 375

complications of HELLP syndrome

Answer 375

liver and renal failure pulmonary oedema DIC placental abruption

Question 376

acute fatty liver of pregnancy

Answer 376

life threatening rare complication of pregnancy deranged LFTs, often accompanied by abnormal coagulation, leukocytosis and hypoglycaemia

Question 377

how does alcohol excess cause thrombocytopenia?

Answer 377

alcohol is a direct bone marrow suppressant thereby inhibiting megakaryocyte development and platelet production.

Question 378

causes of high ESR

Answer 378

inflammation pregnancy anaemia (mild) autoimmune conditions eg. SLE/ RA infections lymphoma/ multiple myeloma some drugs

Question 379

Causes of low ESR

Answer 379

congestive cardiac failure low fibrinogen low plasma protein polycythaemia sickle cell anaemia hyperviscosity leukaemia e.g CLL

Question 380

why may smokers experience polycythaemia

Answer 380

1. increased EPO secretion from hypoxia 2. smokers have reduced plasma volume, thus increasing the relative [Hb] aka Smokers polcythaemia "combined"

Question 381

von willebrands disease is characterized by abnormal platelet aggregation when exposed to what abx?

Answer 381

Ristocetin an abx no longer clinically used causes vWF to bind the gpIb if defective vwf then platelet aggregation does not occur

Question 382

Pel ebstein fever

Answer 382

cyclical fever lasting 1-2 wks in Hodgkins lymphoma rare

Question 383

B symptoms

Answer 383

Fever \>38/ Pel-ebstein fever Night sweats Weight loss: unintential, loss of \>10% of normal body weight over period of 6m or less

Question 384

Stage I hodgkins

Answer 384

single lymph node region involved

Question 385

stage II hodgkins

Answer 385

involvement of two or more LN regions on same side of the diaphragm

Question 386

mild von wellibrands disease scheduled for dental extraction she had one previously where she required 2 units of blood transfused. what is the most appropriate tx prior to surgery?

Answer 386

Desmopressin. acts to increased vWF and fVIII concentration by encouraging its release from endothelial cell storage sites. Not efficacious in type III (profound deficiency in vWF) if mod- severe. Cryoprecipitate - contains vWF and fVIII etc

Question 387

clinical manifestations of Bare Lymphocyte Syndrome apart from recurrent infections/ FTT

Answer 387

sclerosing cholangitis with hepatomegaly and jaundice

Question 388

what does muromonab do (OKT3)?

Answer 388

efficiently clears T cells from the recipients circulation used to treat rejection episodes in patients who have undergone allograft transplantation.

Question 389

immunosuppressive effects of corticosteroids

Answer 389

inhibits prostaglandin formation reduces no of circulating B cells inhibits monocyte trafficking inhibits T cell prliferation reduces expression of inflamatory cytokines e.g. IL 1, TNFa