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Medicine Finals - Imperial & Quick Medical Revision > Haematology AS > Flashcards

Haematology AS Flashcards

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USMLE® Step 1 flashcards
1
Q

What values define anaemia?

A

Males: Hb 140 (<14g/L)
Females: Hb <120 g/L (<12g/L)

Or 125 g/L (<12.5g/dL) in adults.

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2
Q

What are the symptoms of anaemia?

A 
Fatigue
Dyspnoea
Faintness
Palpitations 
Headache
Tinnitus
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3
Q

What are the signs of anaemia?

A 
Pallor
Hyperdynamic circulation 
- Tachycardia
- Flow murmur: apical ESM
- Cardiac enlargement

Ankle swelling with heart failure.

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4
Q

What are the causes of a microcyctic anaemia?

A

Haem defect

  • Iron deficiency anaemia
  • anaemia of chronic disease (because of reduced iron, inadequate secretion of EPO for erythropoiesis, reduced red cell survival). Ferritin is acute phase reactant. Iron is not released from stores therefore despite having low circulating iron, total iron body stores are increased so transferrin is reduced, meaning TIBC is reduced.
  • Sideroblastic/lead poisoning

Globin defect
- Thalassaemia

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5
Q

What are the causes of a macrocytic anaemia?

A

Megaloblastic

  • Vit B12 or folate
  • Anti-folate drugs (phenytoin, methotrexate)
  • Cytotoxic: Hydroxycarbamide

Non-megaloblastic

  • Reticulocytosis
  • Alcohol or liver disease
  • Hypothyroidism (stimulatory effect of thyroid hormones on erythropoiesis).
  • Myelodysplasia
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6
Q

What are the causes of a normocytic anaemia ?

A
  • Recent blood loss
  • Bone marrow failure
  • Renal failure
  • Early ACD
  • Pregnancy (increased plasma volume)
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7
Q

In Haemolytic Anaemia what are the signs of increased red cell breakdown?

A
  • Anaemia with increased MCV + polychromasia = reticulocytosis
  • Increased unconjugated bilirubin
  • Increased urinary urobilinogen
  • Increased LDH
  • Bile pigment stones
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8
Q

What are the signs of intravascular haemolytic anaemia?

A
  • Haemoglobinaemia
  • Haemoglobinuria
  • Decreased haptoglobins
  • Increased urine haemosiderin
  • Increased MCHC
  • Methaemalbuminaemia
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9
Q

What sign indicated extravascular haemolytic anaemia?

A

Splenomegaly (phagocytosis of red blood cells).

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10
Q

What are the acquired haemolytic anaemias?

A

Immune-mediated DAT +ve

  • AIHA: warm, cold,
  • Drugs: penicillin, quinine, methyldopa
  • Allo-immune: acute transfusion reaction, HDFN.
Non-Immune (DAT -ve) 
- PNH 
Mechanical 
- MAHA: DIC, HUS, TTP 
- Heart Valve

Infections: Malaria
Burns

Hereditary

  • Enzyme: G6PD and pyruvate kinase deficiency
  • Membrane: HS, HE
  • Haemoglobinopathy: SCD, thalalassaemia
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11
Q

What are the signs of iron deficiency anaemia?

A
  • Koilonychia
  • Angular Stomatitis/cheiolsis
  • Post-cricoid Web: Plummer-Vinson (IDA, Dysphagia, Oesophageal webs)
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12
Q

What are the causes of IDA?

A

Increased loss: Menorrhagia, GI bleeding, Hookworms

Decreased intake: Poor diet

Malabsorption: Coeliac, Crohn’s

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13
Q

What are the investigations of IDA?

A
  • MCV
  • Reticulocytes

Haematinics:

  • decreased ferritin (correlates with iron stores), - increased TIBC (High as this reflects low iron stores),
  • decreased transferrin saturation (not saturated as free)
  • high transferrin (to bind and carry iron)

Film:
Anisocytosis (size) , poikilocytosis (Shape), pencil cells, hypochromic

Men of any age with a Hb below 110 should be referred for upper and lower GI endoscopy as a 2WW.

  • Upper and Lower GI endoscopy
  • Coeliac screen
  • H.pylori
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14
Q

Management of IDA?

A

Ferrous Sulphate 200mg PO TDS
IV iron for those with Iron deficiency anaemia prior to surgery when oral iron can’t be tolerated or not enou
- SE: GI upset

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15
Q

What is sideroblastic anaemia

A
  • Body has enough Iron, but unable to make haemoglobin.
  • Ineffective erythropoiesis
  • Increased iron absorption
  • Iron loading in BM –> ringed sideroblasts. (Granules of iron in mitrochondria)
  • Haemosiderosis: endo, liver, cardiac damage.
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16
Q

What are the causes of sideroblastic anaemia

A

Congenital
Acquired
- Myelodysplastic/myeloproliferative disease
- Drugs: Chemo, anti-TB, lead.

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17
Q

What are the investigations for Sideroblastic anaemia?

A
  • Microcytic anaemia not responsive to oral iron

- Increased ferritin, increased serum iron, normal TIBC

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18
Q

Management of sideroblastic anaemia?

A

Remove cause

- Pyridoxine may help

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19
Q

What is the pathophysiology of Thalassaemia?

A

Point mutations/deletions –> Unbalanced production of globin chains
–> Precipitations of unmatched globin
Membrane damage –> haemolysis while still in BM and removal by the spleen.

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20
Q

What is the epidemiology of thalassaemia?

A

Common in Mediterranean and Far East (Egyptian girl/Greek man)

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21
Q

What is B-Thalassemia Trait?

A
  • B normal/B + or B/B0 (no production).
  • Mild anaemia usually harmless.
  • Decreased MCV (too low for the anaemia) - <75
  • Increased HbA2 (a2delta 2) and increased HbF (a2y2).
  • HbA2 (>3.5%)

However, there is no history to suggest this and the microcytosis is disproportionately low for the haemoglobin level. This combined with a raised HbA2 points to a diagnosis of beta-thalassaemia trait

Normally seen when fetal haemoglobin transitions to adult haemoglobin.

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22
Q

What is B-Thalassaemia Major?

A
  • Ineffective B-chain therefore severe deficiency in most red-blood cells.
  • Features develop from 3-6 months:
    Severe anaemia
    Jaundice
    Failure to Thrive
    Extramedullary erythropoiesis
  • Frontal bossing
  • Maxillary overgrowth
  • Hepatosplenomegaly

Haemachromatosis after 10yr (transfusion)

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23
Q

What are the investigations for B-thalassaemia major

A
  • Decreased Hb (microcytic) - haemoglobin problem.
  • Decreased MCV
  • Very high HbF
  • V high HbA2
  • High reticulocyte

Film: Target cells (Thalassaemia) and nucleated RBC

Electrophoresis
- Fast migrating are Hb H and Barts.

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24
Q

Management of B-Thall major?

A
  • Life-long transfusion
  • SC- desferrioxamine Fe Chelation
  • Splenectomy
  • BM transplant may be curative
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25
Q

What is a-thalassaemia trait?

A

–/aa or a-/a-
Asymptomatic
Hypochromic microcytes

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26
Q

What is HbH disease

A

–/a-
Moderate anaemia: May need transfusion
Haemolysis: HSM, jaundice

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27
Q

What is Hb Barts

A

–/–

Hydrops fetalis –> Death in utero

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28
Q

What is the investigations for macrocytic anaemia?

A

Film
- B12/Folate
Hypersegmented polymorphonuclear leucocyte
Oval macrocytes

  • Alcohol/Liver
    Target cells.

Blood

  • LFTS: mild increased bili in B12/folate deficiency
  • TFTs
  • Se B12 (<200 pg/ml deficiency)
  • Red Cell Folate: reflects body stores over 2-3 months.
  • Normally low reticulocytes

Biopsy
- If cause not revealed by above tests
Megaloblastic erythropoiesis
Giant metamyelocytes

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29
Q

What are sources of folate?

A

Green veg, nuts and liver

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30
Q

How long do you have stores of folate?

A

4 months

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31
Q

Where is folate absorbed

A

Proximal jejunum

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32
Q

Causes of folate deficiency?

A
  • Decreased intake (poor diet)
  • Increased demand
    Pregnancy
    Haemolysis
    Malignancy
  • Malabsorption
    Coeliac
    Crohn’s
  • Drugs
    EtOH
    Phenytoin
    Methotrexate
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33
Q

Management of folate deficiency?

A
  • Assess for underlying cause
  • Give B12 first unless B12 level known to be normal
    May precipitate or worsen SACD
  • Folate 5mg/d PO.
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34
Q

What are the sources of B12?

A

Source: meat, fish and dairy (vegans get deficiency)

Stores: 4 yrs
Absorption: Terminal ileum bound to intrinsic factor (released from gastric parietal cells).

Role: DNA and myelin synthesis.

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35
Q

What are the causes of B12 deficiency?

A

Decreased Intake - Vegan

Decreased intrinsic factor: Pernicious anaemia, post-gastrectomy

Terminal ileum - Crohn’s ileal resection, bacterial overgrowth.

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36
Q

What are the features of B12 deficiency?

A

General

  • Symptoms of anaemia
  • lemon tinge: pallor + mild jaundice
  • glossitis (beefy, red tongue)

Neuro

  • Paraesthesia
  • Peripheral neuropathy
  • Optic Atrophy
  • SACD
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37
Q

What is subacute combined degeneration of the cord?

A
  • Usually only caused by pernicious anaemia
  • Combined symmetrical dorsal column loss and corticospinal tract loss.
    –> Distal sensory loss: esp joint position and vibration
    Leads to ataxia with wide-gait and +ve Romberg’s test (balance and closing eyes)
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38
Q

What neuro signs do you see in SACD?

A

Mixed UMN and LMN signs

  • Spastic paraparesis
  • Brisk knee jerks
  • Absent ankle jerks
  • Upgoing plantars

Pain and temperature remain intact

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39
Q

What are the investigations to do for B12 Deficiency?

A
  • May have decreased WCC and plats if severe
  • Serum B12
  • Intrinsic factor Abs: specific but lower sensitivity
  • Parietal cells Abs: 90% +ve in PA but less specific.
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40
Q

Management of B12 deficiency ?

A
  • Malabsorption –> parenteral B12 (hydroxocobalamin)
  • Replenish: 1mg/48hr IM
  • Maintain: 1mg IM every 3 months.
  • Dietary –> oral B12 (cyanocobalamin)
  • Parenteral B12 reverses neuropathy but not SACD (injection)
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41
Q

Pernicious Anaemia what is it?

A
  • Autoimmune atrophic gastritis caused by autoabs vs parietal cells or IF –> achlorhydria and decreased IF.
  • Usually >40yr, increased incidence with blood group A

Associated

  • AI: thyroid disease, Vitiligo
  • Ca: 3 risk of gastric adenocarcinoma
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42
Q

What are the AutoImmune Haemolytic Anaemias?

A

Warm = Due to SLE, RA.
Cold
Paroxysmal Cold Haemoglobinuria
Drug: methyldopa, penicillin

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43
Q

What is warm AIHA?

A
  • IgG mediated bind @ 37 C
  • Extravascular haemolysis and spherocytes where it is warm. Occur in the spleen.
  • Ix: DAT +ve, raised LDH = haemolytic anaemia.
  • Causes: idiopathic, SLE, RA, CLL
  • Management: immunosuppression, splenectomy
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44
Q

What is cold AIHI?

A
  • IgM-mediated, binds @ <4C.
  • Often fix complement –> intravascular haemolysis
  • May cause agglutination –> acrocyanosis or Raynaud’s
  • Ix: DAT +ve for complement alone. Causes a macrocytosis due to reticulocytosis.
  • Causes: idiopathic, mycoplasma, background of lymphoma is a risk factor.
  • Rx: avoid cold, rituximab.
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45
Q

What is paroxysmal nocturnal haemaglobinuria?

A
  • Absence of RBC anchor molecule (GP1) –> decreased cell-surface complement degradation proteins –> Intravascular Lysis. (activation of complement on blood cells lacking Complement defence proteins) - exaggerated at night.
  • Affects stem cells and therefore may also –> Decreased platelets and decreased PMN.
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46
Q

What are the features of PNH?

A

Visceral venous thrombosis (hepatic, mesenteric, CNS) - Budd-Chiari,
- IV haemolysis and haemoglobinuria

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47
Q

What are the investigations of PNH?

A
  • Anaemia + thrombocytopenia ± neutropenia

- FACS: decreased CD55 and Decreased CD59

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48
Q

Management of PNH?

A
  • Chronic disorder therefore long-term anticoagulation
  • Eculizumab (prevents complement MAC formation) and controls haemolysis
  • RBC transfusion for underlying aplastic anaemia
  • Erythropoiesis stimulation+ iron tabs.
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49
Q

What are the key features of HUS?

A

E.coli O157
- Bloody diarrhoea + abdo pain precedes:

  • MAHA
  • Thrombocytopenia
  • Renal failure

Ix: Schistocytes, decreased platelets, normal clotting.

Rx:

  • Usually resolves spontaneously
  • Exchange transfusion or dialysis may be needed.
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50
Q

What is Thrombotic Thrombocytopenia Purpura (TTP)

A

Genetic or acquired deficiency of ADAMTS13

Leads to unusually large VWF multimers - lead to platelet aggregation + Subsequent thrombocytopenia.

- Features 
Adult females
Pentad: 
Fever
CNS sign: confusion, seizures
MAHA
Thrombocytopenia 
Renal failure

Ix: schistocytes, decrease platelets, normal clotting

Management - Plasmapheresis, immunosuppression, splenectomy.

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51
Q

What is hereditary spherocytosis?

A

Commonest inherited haemolytic anaemia in N.europe

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52
Q

Pathophysiology of HS?

A
  • Autosomal dominant defect in RBC membrane.

- Spherocytes get trapped in spleen –> Extravascular haemolysis.

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53
Q

What are the features of HS?

A

Splenomegaly
Pigment gallstones
Jaundice

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54
Q

Complications of HS?

A

Aplastic crisis
Megaloblastic crisis
- Leads to a haemolytic criss. Can be caused by erythema infectiosum - due to parvovirus.

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55
Q

What are the investigations of HS?

A
  • EMA binding test - amount of fluorescence derived from individual red cells.
  • Increased osmotic fragility test no longer recommended.
    Normally clinical with spherocytes, raised MCHC.
  • Spherocytes
  • DAT -ve
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56
Q

What is the management of HS?

A

Folate and splenectomy (after childhood). This is primarily an extravascular haemolysis therefore splenomegaly.

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57
Q

What is hereditary eliptocytosis?

A

Autosomal dominant defect –> elliptical RBCs
Most pts are asymptomatic

Rx: folate, rarely splenectomy

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58
Q

G6PD deficiency - pathophsyiology?

A
  • X-linked disorder of pentose phosphate shunt
  • decreased NAPDH production - RBC oxidative damage
  • Affects mainly mediterranean and mid/far east.
  • Therefore turkish and G6PD.
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59
Q

What are the triggers for G6PD

A

Broad (Fava) beans
Mothballs (naphthalene)
Infection
Drugs: antimalarials, dapsone, henna, sulphonamides.

Made worse by fava beans, beans means Heinz and you bite beans so you get bite cells.

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60
Q

Invx for G6PD?

A

Film

  • Irregularly contracted cells
  • Bite cells
  • Heinz bodies (haemolytic anaemia)
  • May have spherocytes as a result of MAHA.

G6PD assay after 8 weeks (reticulocytes have high G6PD).

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61
Q

What is the management of G6PD?

A
  • Treat underlying problem
  • Stop and avoid precipitant
  • Transfusions may be needed.
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62
Q

What is pyruvate kinase deficiency?

A

AR defect in ATP synthesis
–> rigid red cells phagocytosed in the spleen

triggers in times of stress.
Features: Splenomegaly, anaemia ± jaundice

Ix: PK enzyme assay

Rx: often not needed or transfusion ± splenectomy

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63
Q

What is Sickle Cell anaemia

A
  • Point mutation in B globin gene –> Glu to valine.
    SCA: HbSS
    Trait: HbAS
  • HbS insoluble when deoxygenated –> Sickling
  • Sickle cells have decreased life-span –> haemolysis
  • Sickle cells gets trapped in microvascular –> Thrombosis
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64
Q

What are the investigations for SCD?

A
  • Hb 6-9, increased reticulocytes, increased bilirubin. Therefore low haemoglobin, normal MCV, raised reticulocytes. Normocytic anaemia as destruction
  • Film: Sickle cells and target cells. Howell-Jolly Bodies.
  • Hb electrophoresis
    Dx at birth with neonatal screening.
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65
Q

Triggers in Sickle Cell Disease

A
  • Clinical features manifest from 3-6 months due to decreased HbF
  • Triggers
    Infection
    Cold
    Hypoxia
    Dehydration
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66
Q

Presentation in SCD?

A

Splenomegaly: may –> sequestration crisis

  • Infarction: stroke, spleen, AVN, leg ulcers, BM
  • Crises: pulmonary, mesenteric, pain

Thrombotic crises

  • Painful or vaso-occulisve crises due to infection, dehydration deoxygenation.
  • Infarcts occur in various organs including the boen (avascular necrosis of hip, hand-foot syndrome, lungm spleen)

Sequestration crisis
- Sickling within organs such as spleen or lungs poolign blood with worsening anaemia.

Acute chest syndrome
- Dyspnoea, chest pain, pulmonary infiltrates, low pO2.
Most common cause of death after childhood.

Aplastic crises
- Sudden fall in haemoglobin, associated with parvovirus

Haemolytic crisis

  • Rare
  • Fall in haemoglobin due to icnreased ate of haemolysis.
  • Kidney Disease
  • Liver, lung disease
  • Erection
  • Dactylitis
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67
Q

Complications of Sickle Cell disease?

A

Sequestration crisis

  • Splenic pooling –> Shock and severe anaemia (trapping of RBC)
  • Splenic infarction:atrophy
  • Increased infection: osteomyelitis
  • Aplastic crisis: due to parvovirus B19 infection
  • Gallstones
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68
Q

Management of Chronic SCD?

A
  • Pen V BD prophylaxis + immunisations
  • Folate
  • Hydroxycarbamide if frequent crises (in children). Shown to decrease frequency of pain episodes.
  • Consider bone marrow transplant
  • Blood
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69
Q

Management of an acute crises?

A

General

  • Analgesia: opioids IV
  • Good hydration
  • O2
  • Keep warm

Investiation

  • FBC, U+E, reticulocytes, cultures
  • Urine Dip
  • CXR

Management

  • Blind Abx: ceftriaxone
  • Transfusion: Exchange if severe
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70
Q

What pathway does APTT test and which factors?

A 
Intrinsic: 12,11,9,8. 
Common: 10, 5, 2, 1
Assessing secondary haemostasis
Increased: 
- Lupus anticoagulant (Anti-PL) 
- Haemophilia A or B
- vWD (carries factor 8) 
- Unfractionated heparin
- DIC
- Hepatic failure
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71
Q

Which pathway does PT test and which fators?

A

Extrinsic: 7
Common: 10, 5, 2, 1

Increased:

  • Warfarin/ Vit K deficiency
  • Hepatic failure
  • DIC
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72
Q

What does the Bleeding Time test?

A 
Platelet function - primary haemostasis
- Increased in: 
Decreased platelet numbers or function 
-vWD
- Aspirin 
- DIC
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73
Q

What does Thrombin time test?

A 
Fibrinogen function 
- Increased 
Quantitive/qualitative fibrinogen defect 
- DIC, dysfibrinogenaemia 
- Heparin
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74
Q

What are the features of a vascular or platelet disorder?

A

Bleeding into skin: petechiae, purpura, ecchymoses.

Bleeding mucus membranes: Epistaxis, menorrhagia, gums.

Immediate, prolonged bleeding from cuts.

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75
Q

What are the features of coagulation disorders?

A
  • Deep bleeding: muscles, joints, tissues.

- Delayed but severe bleeding after injury.

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76
Q

What are congenital vascular disorders?

A

HHT
Ehler’s Danlos (Easy bruising)
Pseudoxanthoma elasticum (elastic fibre disorder)

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77
Q

What are the acquired vascular disorders

A 
Vasculitis e.g HSP
Steroids 
Infection e.g meningococcus
Vit C deficiency
Senile purpura
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78
Q

How can you classify platelet disorders?

A

Thrombocytopenia

  • Increased destruction
  • Decreased production
  • Spleening pooling

Functional defects

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79
Q

What causes a decreased production of platelets?

A
  • BM failure: aplastic, infiltration of bone marrow, drugs (ETOH, cyto) )
  • Megaloblastic anaemia
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80
Q

What causes increased destruction of platelets?

A
  • Immune: ITP, SLE, CLL, heparin, Viruses.

- Non-immune: DIC, TTP, HUS, PNH, anti-phospholipid

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81
Q

What causes splenic pooling leading to thrombocytopaenia?

A

Portal HTN

SCD

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82
Q

Which anticoagulant do you give for ACS?

A

1st line: Aspirin (lifelong) and ticagrelor 12months

2nd line: if CI aspirin, given clopidogrel lifelong

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83
Q

Which anticoagulant do you give for PCI?

A

1st line: Aspirin (lifelong) and ticagrelor 12months or prasurgrel

2nd line: if CI aspirin, given clopidogrel lifelong

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84
Q

Which anticoagulant do you give for TIA?

A

1st line: Clopidogrel

2nd line: aspirin and dipyridamole

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85
Q

Which anticoagulant do you give for Ischaemic Stroke?

A

1st line: Clopidogrel

2nd line: aspirin and dipyridamole

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86
Q

Which anticoagulant do you give for Peripheral arterial disease?

A

1st line: Clopidogrel (lifelong)

2nd line: Aspirin (lifelong)

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87
Q

What is Immune thrombocytopenia purpura?

A

Children: commonly post

Acute: More commonly seen in children, equal sex incidence, may follow an infection or vaccination, usually runs a self-limiting course over 1-2 weeks.

Chronic ITP: more common in young/middle-aged women. Tends to run a relapsing-remitting course.

Evan’s syndrome: ITP in association with autoimmune haemolytic anaemia (AIHA).

  • URTI, self-limiting.
  • Adults:F>M, long-term
  • Ix: Anti-platelets Abs present
  • Management is conservative with steroids if necessary, consider IVIG/Splenectomy.
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88
Q

What platelet functional defects can lead to a bleeding diatheses?

A 
Drugs: aspirin, clopidogrel
2ndry: paraproteinaemia, uraemia 
Hereditary 
- Bernard-Soulier: GpIb deficiency 
- Glanzmann's: GpIIb/IIIa deficiency.
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89
Q

What can cause an acquired coagulation disorder?

A
  • Severe liver disease
  • Anticoagulants
  • Vitamin K deficiency
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90
Q

What is Haemophilia A: F8 deficiency

A

No Factor 8

  • X-linked, affects 1/5000 males
  • Presentation: Hemarthrosis, bleeding after surgery/extraction.
  • Ix: Increased APTT, normal PT, decreased F8 assay.
  • Mx
    Avoid NSAIDs and IM injection

Minor bleeds: desmopressin + transexamic acid (control mucosal bleeding - antifibrinolytic)

Major bleeds: rhF8.

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91
Q

What is Haemophilia B: F9 deficiency?

A

No Factor 9

X-linked 1/20,000 males.

Consider infusion of IX concentrate.
Antifibrinolytic and pain medication.

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92
Q

What is vWD?

A
  • Commonest inherited clotting disorder (mostly AD)
  • vWF
    Stabilised F8
    Binds pats via GpIb to damaged endothelium.

Ix: If mild, APTT and bleeding time may be normal.
- Increased APTT, Increased Bleeding Time, normal platelets, decreased vWF AG.

Management - Desmopressin and tranexamic acid. Consider VIII concentrate.

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93
Q

What is the presentation of DIC?

A

Acquired syndrome - activation of coagulation pathways, resulting in formation of intravascular thrombi + depletion of platelets + coagulation factors.

Coagulation = fibrinogen to fibrin = fibrin clot.
Fibrinolytic system = breaks down fibrinogen + fibrin. Through generating plasmin in the presence of thrombin to cause lysis of the clot.

Once DIC is triggered, TF present on surface of many cells and is not normally in contact with circulation. When exposed to cytokines lead DIC due to TF binding with coagulation fator + triggering extrinsic pathway.

Thrombin leads to vascular obstruction.

Thrombosis and Bleeding

  • Increased PT, increased APTT, increased TT, decreased platelets, decreased fibrinogen, increased FDP.
  • Schistocytes (MAHA)
  • Thrombosis and bleeding
  • Causes: Sepsis, malignancy, trauma, obs.
  • Management: FFP, Platelets, heparin.
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94
Q

What is the definition of thrombophilia?

A

Coagulopathy predisposing to thrombosis, usually venous.

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95
Q

What are the inherited coagulopathies?

A

Factor V Leiden
Prothrombin gene mutation
Protein C and S deficiency
Antithrombin III deficiency

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96
Q

What is Factor V Leiden

A

Most common thrombophilia - present in 5% of UK population.

Gain of function mutation in the Factor V Leiden protein. Results in a mis-sense mutation means that Factor V is inactivated 10 times more slowly by activated protein C. (activated Protein C resistance). Resistance to action of protein C.

Heterozygotes have 4-5x risk of VTE.
Homozygotes have 10x risk of venous thrombosis.

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97
Q

Protein C and S deficiency?

A

Heterozygotes for either have increased risk of thrombosis
- Skin necrosis occurs - especially with warfarin.

Heterozygotes –> neonatal purpura fulminans.

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98
Q

Antithrombin III deficiency?

A
  • AT is heparin co-factor –> thrombin inhibition
  • Deficiency affects 1/500.
  • Heterozygotes have high risk of thrombosis risk.
  • Homozygosity is incompatible with life.
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99
Q

Acquired thrombophilia from where?

A
  • Progesterone in OCPs, HRT, raloxifen, tamoxifen, antipsychotic (olanzapine).
- Anti-phospholipid syndrome
CLOTs: venous and arterial 
Coagulation defect: 
- increased APTT
- Livido reticularis
- Obstetric complications: recurrent 1st trimester abortion 
- Thombocytopenia.
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100
Q

Indications for a thrombophilia screen?

A
  • Arterial thrombosis <50yrs
  • Venous thrombosis <40yrs with no RFs
  • Familial VTE
  • Unexplained recurrent VTE
  • Unusual site: portal, mesenteric
  • Recurrent foetal loss
  • Neonatal
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101
Q

Investigations for thrombophilia screen?

A
  • FBC, clotting, fibrinogen concentration.
  • Factor V Leiden, APC resistance
  • Pupus anticoagulant and anti-cardiolipin As
  • Assays for AT, protein C and S deficiency
  • PCR for prothrombin gene mutation
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102
Q

What is the management of thrombophilia?

A
  • Manage acute thrombosis as per normal
  • Anticoagulate to INR 2-3
  • Consider lifelong warfarin
  • If recurrence occurs on warfarin increased INR to 3-4.
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103
Q

How do you prevent thrombophilia?

A
  • Lifelong anticoagulation not needed if asymptomatic
  • Increased VTE risk with OCP or HRT
  • Prophylaxis in high risk situations
    Surgery
    Pregnancy
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104
Q

What products can you use for blood transfusion?

A
  • Packed Red cells
  • Fresh Frozen Plasma
  • Cryoprecipitate
  • Platelet rich plasma
  • Platelet concentrate
  • Human Albumin Solution
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105
Q

What are packed red cells used for?

A
  • Stored @ 4C. Less chance of developing an infection.
  • Hct ~70%
  • Use to correct anaemia or blood loss (cases where infusion of large volumes of fluid may result in cardiovascular compromise)
  • 1u → ↑Hb by 1-1.5g/dL
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106
Q

What is platelet rich plasma used for?

A
  • Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery. It is obtained by low speed centrifugation.
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107
Q

What are platelet concentrate used for?

A
  • Not needed if count >20 or not actively bleeding
  • Should be x-matched.
  • Stored at room temperature and must be used soon after collection. Puts them at risk of culturing gram positive organisms.

Administered to patients who are thrombocytopenic.

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108
Q

What is FFP?

A
  • Prepared from single units of blood.
  • Contains clotting factors, albumin and immunoglobulin.
    For patients with pT or APTT >1.5.
  • Unit is usually 200 to 250ml.
  • Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery, TTP, DIC.
  • Usual dose is 12-15ml/Kg-1.
    It should not be used as first line therapy for hypovolaemia.
  • Universal donor for FFP is AB blood because it lacks any anti-A or anti-B.
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109
Q

What is cryoprecipitate?

A
  • Formed from supernatant of FFP.
  • Used to replace fibrinogen <1.5g/L.
  • Rich source of Factor VIII and fibrinogen, vWF, Factor XIII and fibronectin.
  • Allows large concentration of factor VIII to be administered in small volume.
  • EG - DIC, liver failure. Emergency for haemophiliacs and von Willebrand.
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110
Q

What blood products can be used in the reversal of warfarin?

A
  • Stop Warfarin
  • Vitamin K (reverse in 4-24hrs) (IV = 4-6hr, Oral = 24hr).
  • 1st line: Human prothrombin complex (reversal within 1hr, Bereplex. Rapid action byt factor 6 short half life, therefore give with Vit K.
  • FFP (less commonly 1st line). Need to give at least 1L of fluid in 70kg person.
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111
Q

What are the immediate transfusion reactions?

A
  • Haemolytic
  • Bacterial Contamination
  • Febrile Non-haemolytic
  • Allergic
  • TRALI
  • Fluid Overload
  • Massive Transfusion
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112
Q

What is a haemolytic transfusion reaction?

A
  • Occurs in: Minutes
  • Clinical features:
    Agitation, fever, abdo/chest pain, decreased BP, DIC (haemorrhage) renal failure.
  • Mechanism: ABO incompatibility –> IV haemolysis
  • Management: Stop transfusion, tell lab, keep IV line open with NS generous saline, treat DIC.
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113
Q

What is the sign of bacterial contamination in a transfusion?

A
  • Occurs in: <24hrs
  • Clinical features: Increase in temp and rigors. BP down because of shock.
  • Mechanism: Bacterial proliferation, esp platelets.
  • Management: Stop transfusion, send unit to lab, Abx: Taz + gent.
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114
Q

What is febrile non-haemolytic transfusion reaction?

A
  • Occurs in: <24hrs
  • Clinical features: Fever, rigors, chills.
  • Mechanism: Recipient anti-HLA abs.
  • Management: Slow transfusion, Paracetamol 1g.
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115
Q

What is allergic transfusion reaction?

A
  • Occurs in: Immediate
  • Clinical features: Urticaria, itch, angioedema, anaphylaxis
  • Mechanism: Recipient IgA deficiency Anti-IgA IgE
  • Management: Slow, chlorphenamine 10mg IV/IM
    Urticaria = antihistamine.
    More severe allergic reaction = discontinue transfusion, IM adrenaline. Then antihistamine, corticosteroids and bronchodilators should be considered in these patients.
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116
Q

What is TRALI? Transfusion-related acute lung injury?

A
  • Occurs in: <6hr
  • Clinical features: ARDS, SOB, cough, bilateral infiltrates on CXR, fever, hypotension. - KEY IS HYPOTENSION
  • Mechanism: Anti-WBC Abs in donor plasma.
  • Management: Stop transfusion, manage ARDS.
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117
Q

What is TACO (Transfusion associated circulatory overload)

A
  • Occurs in: <6hr
  • Clinical features: CCF. Pulmonary oedema the patient may also by hypertensive, key difference from patients with TRALI.
  • Mechanism:
  • Management: Slow transfusion + 02 + frusemide 40mg IV
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118
Q

What are the delayed transfusion reactions?

A

Delayed haemolytic
Fe Overload
Post-transfusion purpura
GvHD

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119
Q

What is delayed haemolytic transfusion reaction?

A
  • Occurs in: 1-7d
  • Clinical features: Jaundice, Anaemia, decreased Hb, Fever, ± Haemoglobinuria.
  • Mechanism: Recipient anti-Ph Abs + Extravas haemolysis.
  • Management:
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120
Q

What is the Fe Overload symptoms?

A
  • Occurs in: Chronic
  • Clinical features: SCA or Thal Major, Haemochromatosis
  • Mechanism: Chronic Transfusion:
  • Management: Desferrioxamine SC
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121
Q

What is Post-transfusion purpura?

A
  • Occurs in: 7-10 days
  • Clinical features:
    Thrombocytopaenia, purpura.
  • Mechanism: AlloAbs attack recipients + donor plats
  • Management: IVIG + Platelet transfusion
122
Q

What is GvHD?

A
  • Occurs in: 4-30d
  • Clinical features: Diarrhoea, skin rash, liver failure –> Increased LFTs, pancytopaenia
  • Mechanism: Viable lymphocytes transfused into immunocompromised host. Irradiate blood for vulnerable hosts.
  • Management:
123
Q

What are the congenital causes of pancytopenia?

A

Fanconi’s anaemia: Aplastic anaemia

124
Q

What are the acquired causes of pancytopenia?

A 
Idiopathic aplastic anaemia 
BM infiltration 
Haematological causes: 
- Leukaemia
- Lymphoma
- Myelofibrosis
- Myelodysplasia
- Megaloblastic anaemia

Infection: HIV
Radiation

Drugs

  • Cytotoxic: cyclophos, azathioprine, methotrexate
  • Abx: chloramphenicol, sulphonamides
  • Diuretics: Thiazide
  • Anti-thyroid: carbimazole
  • Anti-pscyhotic: clozapine
  • Anti-epileptic: phenytoin
125
Q

What are the key features of aplastic anaemia?

A
  • Pancytopenia
  • Hypocellular marrow

Presentation: Pancytopenia

  • Age: 15-24yrs and >60yrs
  • Anaemia
  • Infection
  • Bleeding
126
Q

Inherited Causes of Aplastic anaemia?

A

Inherited

  • Fanconi’s anaemia: Ashkenazi, short, pigmented.
  • Dyskeratosis congenita: premature ageing
  • Swachman-Diamond Syndrome: pancreatic exocrine dysfunction.

Sometimes associated wtih PNH

127
Q

What are the acquired causes of aplastic anaemia?

A

Drugs
Viruses: Parvovirus, hepatitis
Autoimmune: SLE.

128
Q

Investigations for BM failure?

A

Hypocellular marrow.
Low WBC, Low Hb, Low Platelets

  • Must have haemoglobin less than 100
  • Platelets <50
  • Neutrophils <1.5
  • Bone marrow show hypocellularity without evidence of dysplasia, blasts, fibrosis.
  • Low reticulocyte count
129
Q

Management of aplastic anaemia ?

A
  • Supportive: transfusion
  • Immunosuppression: anti-thymocyte globulin
  • Allogeneic BMT: may be curative
130
Q

What is myelodysplastic syndrome?

A

Pathophysiology?

  • Heterogeneous group of disorders –> BM failure
  • Clone of stem cells with abnormal development
  • -> Functional defects
  • -> quantitative defects

May be primary or secondary
- Chemo or radiotherapy

Characteristic

  • Cytopenias
  • Hypercellular BM
  • Defects cells: Ringed sideroblasts
  • 30% AML

Clinical feature s

  • Elderly
  • BM failure: anaemia, infection, bleeding, bruising.
  • Splenomegaly

Investigations

  • Film: BLast, Pelger-Huet anomaly, dimorphic
  • BM: Hypercellular, blast, ringed sideroblasts.

Mx

  • Supportive: transfusion, EPO, G-CSF
  • Immunosuppression
  • Allogeneic BMT: may be curative
131
Q

What are the chronic myeloproliferative disorders?

A

RBC –> Polycythaemia Vera
WBC –> CML
Platelets –> Essential thrombocythemia
Megakaryocytes –> Myelofibrosis

132
Q

Polycythaemia Vera - what are the features?

A

PV due to increase in RBC, also neutrophils + platelts.

Hyperviscosity

  • Headache
  • Visual disturbances
  • Tinnitis
  • Thrombosis
  • -> arterial: strokes, TIA, peripheral emboli)
  • -> Venous: DVT, PE, Budd-Chiari

Histamine Release
- Aquagenic pruritus
Erythromelalgia
- Sudden, severe burning in hands and feet with redness of the skin

Splenomegaly
- 75%
Hepatomegaly
- 30%

Gout

133
Q

Investigations for polycythaemia vera?

A

1st line - 99% JAK2 +ve. (if -ve lok for secondary cause due to EPO, Abdo US, Arterial Oxygen saturation.

  • Increased RBC, Hb ad HCt
  • Increased WCC and
  • increased platelets
  • Ferritin
  • EPO normally low

May also have low ESR and raised leukocyte alkaline phosphatase

  • BM: hypercellular with erythroid marrow
  • Decreased ERP
  • Increased red cell mass with isotope studies.
134
Q

Management of PV?

A

Aim for Hct <0.45 to decrease thrombosis

  • Aspirin 75mg OD
  • Venesection if young
  • Hydroxyurea - slight increased risk of secondary leukaemia
  • Hydroxycarbamide if older/higher risk.
  • Phosphorus-32 therapy.
135
Q

What is true polycythaemia ?

A

Increased in total volume f red cell

  • Primary: PV
  • Secondary: Hypoxia, COPD, smoking. EPO: renal cysts/tumours. Due to raised EPO.
136
Q

What is false polycythaemia?

A

Decreased plasma volume

  • Acute = dehydration, shock, burns.
  • Chronic = Diuretics, smoking.
137
Q

What is essential thrombocythaemia?

A

Features

  • Thrombosis
  • Bleeding (abnormal plat function). E.g mucus membranes
  • Erythromelagia (burning + redness in hands) - typical feature.
138
Q

What are the investigations for Essential thrombocytopenia ?

A
  • Platelets >600 (often >1000)
  • BM: increased megakaryocytes.
  • 50% JAK2 +ve.
139
Q

What is the management of ET?

A
  • Platelets 400-1000: aspirin alone
  • Thrombosis or plate >1000: hydroxycarbamide
  • Anagralide may be used
  • inhibits platelet maturation
  • Decreased platelet count and function
140
Q

What is the differential for thrombocythaemia?

A
  • Primary: ET
  • Secondary:
    Bleeding,
    infection,
    chronic inflammation: RA, IBD
    Trauma/surgery
    Hyposplenism/splenectomy
141
Q

What is primary myelofibrosis?

A
  • Clonal proliferation of megakaryocytes –> increased PDGF –> Myelofibrosis
  • Extramedullary haematopoiesis: liver + spleen.
142
Q

What are the features of primary myelofibrosis?

A

Elderly
Massive HSM
Hypermetabolism: weight loss, fever, night sweats.
BM failure: Anaemia, infections, bleeding

143
Q

Investigations for primary myelofibrosis?

A

Film: Leukoerythroblastic with teardrop poikilocytes.

  • Cytopenias
  • BM: dry tap (need trephine biopsy)
  • 50% have JAK+ve.
144
Q

Management of primary myelofibrosis?

A
  • Supportive: blood products
  • Splenectomy
  • Allogeneic BMT may be curative in younger patients.
145
Q

What is the demographic of acute lymphoblastic leukaemia?

A
  • Children 2-5 yr (commonest childhood Ca)

- Rare in adults

146
Q

What is the aetiology of ALL?

A
  • Arrest of maturation + proliferation of lymphoblasts.

- 80% B lineage, 20% T lineage.

147
Q

What are the risk factors of ALL?

A

Genetic susceptibility (ofen Chr Translocation)
Environmental trigger
- Radiation (during pregnancy)
- Down’s

148
Q

What are the features of ALL?

A
  • BM failure (anaemia, thrombocytopenia, leucopenia)
  • Infiltration (lymphadenopathy, orchidomegaly, thymic enlargement, HSM, CNS (CN palsies, meningism), Bone pain.
  • Fever is common
149
Q

Investigations for ALL?

A

Low threshold for children with leukaemia - suspicious of leukaemia with a blood test in 48hrs.

If hepatosplenomegaly or unexplained petichie - immediate assessment should occur.

  • Increased WCC: Lymphoblasts (on peripheral film)
  • Decreased RBC, decreased PMN, decreased platelets
  • BM aspirate
    >20% blasts
    Cytogenetic and molecular analysis

CXR + CT: mediastinal + abdo lymph
LP: CNS involvement

150
Q

Management for ALL?

A

Supportive

  • Blood products
  • Allopurinol
  • Hickman line or Portacath

Infections

  • Gentamicin + Tazocin
  • Prophylaxis: e.g co-trimoxazole, cipro
Chemo 
- Remission induction (dexa/cristantaspase/vincristine) 
(Imatinib?) 
- Consolidation + CNS Management 
- Maintenance for 2-3 yrs.

Consider BMT

151
Q

What is Acute Myeloid Leukaemia?

A
  • Increased risk with age: mean = 65-70.
  • Commonest acute leukaemia of adults.

APML - presents 25yrs old.

152
Q

What is the aetiology of AML?

A

Neoplastic proliferation of myeloblast.

Fusion of PML and RAR-alpha genes.

Risk factors

  • Chromosomal abnormalities
  • Radiation
  • Down’s
  • Chemo
  • Myelodysplastic and myeloproliferative syndromes?

FAB classification

  • M2: granulocyte maturaiton
  • M3: acute promyeloctyic leukaemia - t(15:17)
  • M4: acute myelomonocytic leukaemia
  • M7: megakaryoblastic leukaemia
153
Q

What are the features of AML?

A
  • BM Failure - Cytopenia

- Infiltraiton –> Hypertrophy + bleeding (M4), HSM, skin involvement, bone pain.

154
Q

What to see on blood in AML?

A

DIC: APML (M3) = fusion of t(15;17) -PML - RAR alpha gene.
Hyperviscosity: Increased WBC may –> thrombi

155
Q

What investigations do you do for AML?

A 
Increase WCC blast (occassionally normal) 
ANaemia and decreased platelet 
BM aspirate 
- >20% blasts 
- Auer rods are diagnostic

Dx - Made by immunological and molecular phenotyping
= Flow cytometry
- Cytogenetic analysis affects management and guides prognosis.

156
Q

Management of AML?

A

Supportive
- Blood products
Allopurinol
Hickman line or Portacath

  • Infections
    Gentamicin + tazocin
    Prophylaxis: e.g. co-timoxazole, ciprofloxacin

Chemo

  • V.intensive –> Long periods of neutropenia and decreased platelets
  • ATRA for APML
157
Q

BMT for AML?

A

Allogeneic if poor prognosis

  • Destroys BM and leukaemic cells with chemotherapy and total body irradiation.
  • repopulates marrow with HLA-matched donor HSC.

Autologous if intermediate prognosis
- HSC taken from patient.

158
Q

What is the epidemiology of lymphocytic leukaemia

A

Commonest leukaemia in Western World
M>F = 2:1
Elderly: 70s.

159
Q

Aetiology of CLL?

A

Clone of mature B cells (memory cells).

160
Q

Features of CLL

A
  • Often asymptomatic incidental finding
  • Symmetrical painless lymphadenopathy
  • HSM
  • Anaemia
  • B symptoms: weight loss, fever, night sweats.
161
Q

Complications of CLL?

A
  • Autoimmune haemolysis (warm autoimmune haemolysis)
  • Evan’s = AIHA and ITP
  • Infection (decreased Ig):
    bacterial, zoster
  • Marrow Failure/infiltration.
  • Hypogammaglobulinaemia leading to recurrent infections

Transformation to high-grade lymphoma (Richter’s transformation). Non-Hodgkin’s lymphoma. Diffuse Large B cell non-Hodgkin’s lymphoma.

Warm AIHA.

162
Q

Investigations of CLL

A
  • Increased WCC, Lymphocytosis
  • Smear cells (Crushed little lymphocytes)
  • Decreased serum Ig
  • +ve DAT
  • Rai or Binet Staging

Immunophenotyping to distinguish from NHL

163
Q

What is the natural history of CLL?

A
  • Some remain stable for years
  • Nodes usually enlarge slowly (± lymphatic obstruction)
  • Death often due to infection e.g encapsulates, fungi
  • Richter Transformation: CLL –> large B cell lymphoma.
164
Q

What is the management of CLL?

A

Indications for treatment

  • Symptomatic
  • Ig genes un-mutated (bad prognostic indicator)
  • 17p deletions (bad prognostic indicator)

Supportive care

Chemotherapy

  • Cyclophosphamide
  • Fludarabine
  • Rituximab

Radiotherapy
- Relieve LN or splenomegaly

165
Q

Prognosis for CLL?

A

1/3 never progress
1/3 progress with time
1/3 are actively progressing

166
Q

CML epidemiology?

A

15% of leukaemia

Middle aged- 60-70yrs

167
Q

Aetiology of CML?

A

Myeloproliferative disorder: clonal proliferation of myeloid cells.

168
Q

Features of CML?

A

Systemic: weight loss, fever, night sweats, lethargy.

Massive HSM –> Abdo discomfort

Bruising/bleeding (Platelet dysfunction) - an increased in granulocytes at different stages of maturation +/- thrombocytosis.
Decreased leukocyte alkaline phosphatase.
Gout
Hyperviscosity

169
Q

What is the philadelphia chromosome?

A

Reciprocal translocation: t(9,22)
Formation of BCR-ABL fusion gene.
- Constitutive tyrosine kinase activity.
Present in >80% of CML

170
Q

Investigations for CML?

A

High WBC

  • PMN and basophils
  • Myelocytes (Increase in granulocytes at different stages of maturation)
  • Decreased leukocyte alkaline phosphatase.
  • ± decreased Hb and decreased platelets (increased platelets as they are produced by megakaryocytes which are in the myeloid line) .
    (accelerated or blast phase)
  • Increased urate
  • BM cytogenetic analysis: Ph +ve.
171
Q

What is the natural history of CML?

A

Chronic phase <5% blast in blood or DM

Accelerated phase: 10-19% blasts.

Blast crisis: usually AML, >20% blasts.

172
Q

Management of CML?

A

Imatinib: tyrosine kinase inhibitor

  • 90% haematological response
  • 80% 5yrs

Allogeneic SCT
- Indicated if blast crisis or TK-refractory.

173
Q

Non-Hodgkin’s Lymphoma (80%) - What are the features?

A

Much moe common than Hodgkin’s

Lymphadenopathy: 75% at presentation

Extranodal - skin, gastric (dyspepsia, dysphagia, weight loss, abdo pain), bone marrow, lungs, skin)

B-symptoms

174
Q

What are the features of lymphadenopathy in NHL

A

Painless
Symmetrical
Multiple sites
Spread discontinuously

175
Q

What are the extranodal features of NHL?

A

Skin: esp T cell lymphoma
CNS (nerve palsy)
Oropharynx and GIT (dyspepsia, dysphagia, weight loss, abdo pain)
Splenomegaly

176
Q

Risk factors of NHL?

A
  • Elderly
  • Caucasians
  • History of viral infection (EBV)
  • Family History
  • Certain chemical agents (pesticides, solvents)
  • History of chemo or radio
  • Immunodeficiency (HIV, transplant, diabetes mellitus, Hep C)
  • Autoimmune disease (SLE, Sjorgren’s,coeliac disease) -
  • HHV8
177
Q

What to see on blood test for NHL?

A

Pancytopenia
Hyperviscosity
Nucleated red blood cells, left shift
Lymph node biopsy +ve.

178
Q

Investigations for NHL?

A
  • FBC, U+E, LFTs, LDH
    (increased LDH = worse prognosis)
  • Film: Normal or circulating lymphoma cells ± pancytopenias
    -Classification: LN + BM biopsy
  • Staging: CT/MRI chest, abdomen, pelvis
  • Use the Ann Arbor System
179
Q

Classification of low-grade B cell NHL?

A

B Cell most common.

Usually indolent but often incurable

  • Follicular (BCL-2)
  • Small cell lymphoctyic (CLL)
  • Marginal Zone
  • Lymphoplasmacytoid (Waldenstrom’s)
180
Q

Classification of high-grade B cell NHL?

A

Aggressive by may be curable

  • Diffuse large B cell (most common) - Cyclin D1-IGH
  • Burkitt’s (C-Myc) - t(8:14).
181
Q

What are the T cell NHLs?

A
  • Adult T cell lymphoma: caribs and japs - HTLV-1
  • Enteropathy- associated: T cell lymphoma: Chronic coeliacs
  • Cutaneous T cell lymphoma: Sezary syndrome
  • Anaplastic large cell
182
Q

Management of NHL?

A

MDT

High-grade

  • R-CHOP regime
  • BMT for relapse
  • ~30% 5 yrs.

Low grade

  • Rx when clinically indicated (chloambucil)
  • Consider radiotherapy/chemo with rituximab/cyclophoshamide)
  • > 50% 5 yrs.
183
Q

What is Hodgkin’s Lymphoma (20%)

A
  • M>F= 2:1 (esp in paeds)
    Bimodal age incidence: 20-29 and >60yrs.
    May be assoc with EBV.
184
Q

What are the features Hodgkin’s Lymphoma?

A

Lymphadenopathy
B symptoms
Others

185
Q

What are the features of lymphadenopathy in Hodgkin’s

A

-Painless
- Asymmetric
- Spreads contiguously to adjacent LN
- Cervical Nodes in 70% (also axillary and inguinal)
- May be alcohol-induced LN pain (KEY DIFFERENCE)
- Mediastinal LN may –> mass effect
SVC obstruction
Bronchial obstruction

186
Q

What are the B symptoms of Hodgkin’s lymphoma?

A

Fever
Night sweats
Weight loss (>10%)

Associated with poor prognosis

Others include

  • Age >45
  • Stage IV
  • Haemoglobin <10.5
  • Lymphocyte count <600 or <8%
  • Male
  • Albumin <40
  • WBC >15,000
187
Q

What are the extranodal features of Hodgkin’s lymphoma?

A
  • Itch
  • Pel Ebstein fever: Cyclical fever
  • Hepato-and/or spleno-megaly
188
Q

Investigations for Hodgkin’s Lymphoma?

A
  • FBC, Film, ESR, LFTs, LDH, Ca
  • Increased ESR or decreased Hb = worse prognosis
  • LN excision biopsy or FNA
    = Reed-Sternberg Cells (owl’s eye nucleus)
  • Staging: CT/MRI chest, abdomen, pelvis
  • BM biopsy if B symptoms or Stage 3/4 disease.
189
Q

What is the staging for Hodgkin’s Lymphoma?

A
  1. Single LN region
  2. > 2 nodal areas on same side of diaphragm
  3. Nodes on both sides of diaphragm
  4. Spread beyond nodes e.g liver, BM
    + B if constitutional symptoms.
190
Q

What are the subtypes of Classical Hodgkin’s Lymphoma

A

Nodular Sclerosing Hodgkin Lymphoma - Good prognosis, associated with lacunar cells.

Mixed-Cellularity Hodgkin -Lymphoma - associated with reed-sternberg cells.

Lymphocyte-Depleted (worst prognosis) - typically with young adults aged 30-37.

Lymphocyte-rich classical 
Hodgkin Lymphoma (best prognosis)

A Reed Sternberg cell may be identified histologically.

191
Q

Management of Hodgkin’s Lymphoma?

A

Chemo, radio or both
ABVD regimen
BMT for relapse.

192
Q

Prognosis of Hodgkin’s Lymphoma?

A

1A: >95% 5yrs
4B: <40% 5 yrs.

193
Q

What is the epidemiology of Multiple Myeloma?

A

M=F
Blacks >White = 2:1
~70yrs.

194
Q

What is the pathogenesis of multiple myeloma?

A

Clonal proliferation of plasma cells –> Monoclonal increase in Ig
–> usually IgG or IgA.

Clones may also produce free light chain ~2/3

  • Excreted by Kidney –> Urinary BJP
  • Light chains only seen in plasma in renal failure

Clones produce IL-6 which inhibits osteoblast (normal ALP) and activates osteoclasts.

195
Q

What are the symptoms of multiple myeloma?

A
  • Osteolytic bone lesions
  • BM infiltration (anaemia, neutropenia, thrombocytopenia)
  • Recurrent Bacterial Infections (neutropenia, immunoparesis, chemo)
  • Renal Impairment (light chain, increased Ca, AL-Amyloid)
  • Complications

CRABBI - Calcium, Renal, Anaemia, Bleeding, Bones, infection

Raised ESR and osteoporosis.

196
Q

How to do osteolytic bone lesions present?

A

Backache and bone pain
Pathological fractures
Vertebral collapse

197
Q

What are the complications of Multiple Myeloma?

A

Hypercalcaemia (signs of hypercalcaemia - stones, moans, groans)
Neurological: increased Ca, Compression, amyloid
AKI
Hyperviscosity
AL-amyloid (15%).

198
Q

What are the investigations for Multiple Myeloma?

A
  • Do ESR and Se eletrophoresis if >50 with back pain.

Blood:

  • FBC: Normocytic normochromic anaemia
  • Film: rouleaux ± plasma cells ± cytopenias
  • Increased ESR, increased U+Cr, increased Ca, Normal ALP. (Raised in mets). Shouldn’t
  • Se electrophoresis and B2-Microglobulin. - Serum free light-chain assay

Clinicians should offer very urgent electrophoresis and Bence Jones protein urine test.

Urine: Increased specific gravity (BJP doesn’t show
- Electrophoresis: BJP

BM trephine biopsy - DIAGNOSTIC TEST = monoclonal plasma cell infiltration in bone marrow.

Imaging

  • Full skeletal survey
  • Punched-out lytic lesions
  • Rain-drop skull
  • Vertebral collapse
  • Fractures

Whole body MRI (or CT if MRI is not suitable)

199
Q

How do you diagnose multiple myeloma?

A

Need 1 major and 1 minor or 3 minor

Major

  • Clonal BM plasma cells >30%
  • Presence of se and/or urinary monoclonal protein
  • PLasmacytoma

Minor

  • 10% to 30% plasma cells in a bone marrow sample.
  • Minor elevations in the level of M protein in the blood or urine.
  • Osteolytic lesions (as demonstrated on imaging studies).
  • Low levels of antibodies (not produced by the cancer cells) in the blood.

Hypercalcaemia in myeloma
primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels

End-organ Damage: CRAB (1 or more) 
CRAB 
- Ca increased (>2.6mM) 
- Renal insufficiency 
- Anaemia (<10g/dL) 
- Bone lesions
200
Q

What is the management of MM?

A

Supportive Management

  • Bone pain: analgesia (avoid NSAIDs) + bisphosphonates
  • Anaemia: transfusions and EPO
  • Renal impairment: Ensure good hydration ± dialysis. Beware that NSAIDs can precipitate renal failure in patients with MM.
  • Infection: broad spectrum Abx ± IVIg if recurrent.

Complications

  • Ca increase: hydration, frusemide, bisphosphonates (fractures + osteoporosis)
  • Cord compression: MRI, dexamethasone + local radio
  • Hyperviscosity: Plasmapheresis (remove light chains) + VTE prophylaxis
  • AKI: rehydration ± dialysis

Specific
- Fit patients
= Induction chemo: lenalidomide/thalidomide + low-dose Dex
Then allogeneic BMT

Unfit Patients

  • Chemo only: melphalan + pred + lenalidomide
  • Bortezomib for relapse
201
Q

What is the prognosis of multiple myeloma?

A

Mean survival: 3-5 yrs
Poor prognostic indicators
- Increased B2-microglobulin
- decreased albumin

202
Q

What is smouldering/asymptomatic myeloma?

A
  • Se monoclonal protein and/or BM plasma cell >10%

- No CRAB

203
Q

What is MGUS?

A

Monoclonal gammopathy of undetermined significance

  • Se monoclonal protein <30 g/L
  • Clonal BM plasma cells <10%
  • No CRAB.
204
Q

What is Waldenstrom’s Macroglobulinaemia

A
  • Lymphoplasmacytoid
  • lymphoma - monoclonal IgM band
  • Features: Hyperviscosity: CNS, ocular symptoms
  • lymphadenopathy + splenomegaly

Ix: Increased ESR, IGM paraprotein.

205
Q

What is primary AL Amyloid

A
  • Occult proliferation of plasma cells –> Production of amyloidogenic monoclonal protein.
  • Se or urinary light chains
206
Q

What is paraproteinaemia in leukaemia

A

Seen in 5% of CLL.

207
Q

What is amyloidosis?

A
  • Group of disorders characterised by extracellular deposits of a protein in an abnormal fibrillar form that is resistant to degradation.
208
Q

What is AL amyloidosis?

A

Clonal proliferation of plasma cells with production of amyloidogenic light chains
Primary: occult plasma cell proliferation
2ndry: Myeloma, Waldenstrom’, MGUS, Lymphoma.

209
Q

What is the features of AL amyloidosis?

A

Vascular: periorbital purpura (characteristic).

Renal: proteinuria and nephrotic syndrome

Heart: restrictive cardiomyopathy, arrhythmias, echo.
- Sparkling appearance on echo

Nerves: Peripheral and autonomic neuropathy, carpal tunnel

GIT: macroglossia, malabsorption, perforation, haemorrhage, hepatosplenomegaly, obstruction.

210
Q

What is AA Amyloidosis?

A

Amyloid derived from serum amyloid A
- SAA is an acute phase protein therefore inflammation

Chronic inflammation

  • RA
  • IBD
  • Chronic infection: TB, chronic
211
Q

What are the features of AA amyloidosis?

A

Renal: proteinuria and nephrotic syndrome

Hepatosplenomegaly

212
Q

Familial Amyloidosis

A
  • Group of AD disorders caused by mutations in transthyretin (produced by liver)
  • Features: Sensory or autonomic neuropathy
213
Q

Others: non-systemic amyloidosis?

A

B-amyloid: Alzheimers
B2-microglobulin: chronic dialysis
Amylin: T2DM

214
Q

Diagnosis of amyloid?

A

Biopsy of affected tissue

  • Rectum or subcut fat is relatively non-invasive
  • Apple-green birefringence with Congo Red Stain under polarised light.
215
Q

Management of Amyloidosis

A
  • AA amyloid may improve with underlying condition
  • AL amyloid may respond to therapy for myeloma
  • Liver Tx may be curative for familial amyloidosis.
216
Q

Prognosis for Amyloidosis

A

1-2 yrs.

217
Q

Complications of haematological malignancies?

A

As a result of being neutropenic - risk for symptoms or signs indicating possible infection such as dysuria, diarrhoea, productive cough.

Neutropenic sepsis
- Neutrophil count of <0.5 x10^9. Temp of >38, other signs consistent with clinically significant sepsis.
Offer broad spectrum antibiotics empirically.

- General precautions 
Barrier nursing in a side room 
Avoid IM injections (may --> infected haematoma) 
Swabs + septic screen
TPR 4hrly.

Antimicrobials

  • Start broad spectrum Abx: check local guidelines.
  • Give piperacillin with tazobactam.
  • Consider G-CSF (Not routinely used) eg Filgrastim = used to treat neutropenia.
218
Q

What can cause a hyperviscosity syndrome?

A
  • Increased RBC/Hct >0.5 e.g PV
  • Increased WCC >100: e.g leukaemia
  • Increased plasma proteins: myeloma, Waldenstrom’s.
219
Q

Features of hyperviscosity syndrome?

A
  • CNS: headache, confusion, seizures, faints
  • Visual: retinopathy –> visual disturbance
  • Bleeding: mucus membranes, GI, Gu
  • Thrombosis
220
Q

Investigations of hyperviscosity syndrome?

A
  • Increased plasma viscosity (PV)
  • FBC, Film, clotting
  • Se + urinary protein electrophoresis
221
Q

Management of hyperviscosity syndrome?

A

Polycythaemia: venesection
Leukopheresis: Leukaemia
- Avoid transfusing before lowering WCC
Plasmapheresis: myeloma and Waldenstrom’s.

222
Q

What is DIC?

A
  • Widespread activation of coagulation from release of pro-coagulants into the circulation
  • Clotting factors and plats are consumed –> bleeding.
  • Fibrin strands –> Haemolysis
223
Q

Causes of DIC?

A

Malignancy - APML
Sepsis
Trauma
Obstetric events: E.g PET

224
Q

Signs of DIC?

A

Bruising
Bleeding
Renal failure

225
Q

Ix for DIC

A 
Decreased platelets
APTT Increased
PT increased
FDP increased 
Decreased fibrinogen
226
Q

Management of DIC

A

Treat cause
Replace: cryoprecipitate, FFP
Consider heparin and APC

227
Q

What is Tumour Lysis Syndrome

A

Massive cell destruction
- High count leukaemia or bulky lymphoma

  • Increased K, urate increased –> renal failure
  • Abnormalities in two or more - uric acid >475 umol or 25%
  • Potassium >6
  • Phosphate >1.125
  • Calcium <1.75

Prevention: Increased fluid intake + allopurinol. May als

228
Q

What is the anatomy of the spleen?

A
  • Intraperitoneal structure lying in the LUQ
  • MEasures 4x11x12 cm
  • Weight 7 pounds

Lies anterior to ribs 9-11.

229
Q

What are the features of a spleen on examination

A
  • Dull to percussion
  • Enlarges to RIF
  • Moves inferiorly on respiration
  • Can’t get above it
  • Medial notch
230
Q

Function of the spleen?

A
  • Part of the mononuclear phagocytic system
  • Phagocytosis of old RBC, WBC, and opsonised bugs.
  • Antibody production
  • Haematopoiesis
  • Sequestration of formed blood elements
231
Q

Causes of Massive Splenomegaly: >20cm

A
  • CML
  • Myelofibrosis
  • Malaria
  • Leishmaniasis
  • Gaucher’s (AR, glucocerebrosidase deficiency)
232
Q

All causes of splenomegaly

A

Haematological

  • Haemolysis: Hereditary Spherocytosis
  • Myeloproliferative disease: CML, MF, PV
  • Leukaemia, lymphoma

Infective

  • EBV, CMV, hepatitis, HIV
  • TB, infective endocarditis

Portal HTN: cirrhosis, Budd-Chiari

Connective tissue: RA, SLe, Sjogrens

Other

  • Sarcoid
  • Amyloidosis
  • Gaucher’s
  • 1 AB deficiency (CVID)
233
Q

Splenectomy leads to hyposplenism (Indications for this?)

A

Indications

  • Trauma
  • Rupture
  • AIHA
  • ITP
  • HS
  • Hypersplenism
234
Q

Complications of splenectomy?

A
  • Redistributive thrombocytosis –> early VTE
  • Gastric dilatation (ileus)
  • Left lower lobe atelectasis: v common
  • Increased susceptibility to infection
  • Encapsulates; haemophilus, pneumo, meningo
235
Q

Film on splenectomy?

A

Howell-Jolly bodies.
Siderocytes
Pappenheimer bodies
Target cells

236
Q

Management of splenectomy?

A

Immunisations: pneumovox, HIB, Men C, yrly flu. Pneumococcal every 5 years.

Daily Abx: Pen V or erythromycin
Warning: Alert card and/or bracelet

237
Q

Other causes of hyposplenism

A

SCD
Coeliac disease
IBD

238
Q

What does ESR mean?

A

How far RBC fall through anti-coagulated blood in 1hr

Normal: ~20mm/h (M:age/2 F: (age+10)/2

Increased serum proteins cover RBCs –> clumping –> rouleaux –> faster settling –> increased ESR.

239
Q

Causes of raised ESR?

A

Plasma factors

  • increased fibrinogen: inflammation
  • Increased globulin: myeloma

Red cell factors
- Anaemia –> increased ESR.

240
Q

Differential of ESR >100

A 
Myeloma 
SLE
GCA
AAA
Ca prostate
241
Q

What are the causes of a neutrophilia?

A
  • Bacterial infection
    left shift, toxic granulation, vacuolation
  • Stress: trauma, surgery, burns, haemorrhage
  • Steroids
  • Inflammation: MI, PAN
  • Myeloproliferative disorders: e.g CML
242
Q

Causes of a neutropenia?

A
  • Bone marrow infiltration
  • Drugs: chemo, cytotoxic, carbimazole, sulphonamides
  • Severe sepsis
  • Hypersplenism: Felty’s
243
Q

Causes of lymphocytosis?

A
  • Viral infection: EBV, CMV
  • Chronic infection: TB, Brucella, Hepatitis, Toxo
  • Leukaemia, lymphoma: esp CLL
244
Q

Causes of lymphopenia?

A

Drugs: steroids, chemo

HIV

245
Q

Causes of a monocytosis?

A
  • Chronic infection: Tb, Brucella, Typhoid

- AML

246
Q

Causes of a eosinophila?

A

Parasitic infection
Drug reaction e.g EM
Allergies: asthma, atopy, Churg- Strauss
Skin Disease: Eczema, psoriasis, pemphigus

247
Q

Causes of Basophila?

A

Parasitic infection
IgE-mediated hypersensitivity: urticarial, asthma
CML

248
Q

What disease would you see acanthocytes? (Spiked cells)

A

Abetalipoproteinaemia

Alcoholic liver disease

249
Q

What disease would cause basophilic stippling?

A

Lead poisoning

Thalassaemia

250
Q

What disease would cause blast production

A

Leukaemia

251
Q

What disease would cause Burr Cells?

A

Uraemia

252
Q

What disease would cause dimorphic picture cells?

A

Myelodysplasia

253
Q

What disease would cause Howell-Jowel Bodies

A

Hyposplenism

254
Q

What disease would cause Heinz bodies

A

G6PD - damage to cell

255
Q

What disease would cause irregularly contracted cells

A

G6PD

256
Q

What disease would cause leukoerythroblastic film

A

BM inflitration

257
Q

What disease would cause Pappenheimer bodies?

A

Hyposplenism

258
Q

What disease would cause pencil cells?

A

IDA

259
Q

What disease would cause reticulocytes

A

Haemolysis

Haemorrhage

260
Q

What disease would cause spherocytes

A

HS

AIHA

261
Q

What disease would cause schistocytes

A

MAHA

Prosthetic valves

262
Q

What disease would cause Target cells

A

Hyposplenism
Thalassaemia
Liver Disease

263
Q

Tear-drop cells/ Dacrocytes

A

BM infiltration and myelofibrosis.
- Collagen gets deposited in the bone marrow, regular stem cells still produce RBCs.

These cells have to squeeze through meshwork of fibrosed marrow, become mischapen and form tear drop cells on film

264
Q

Cytochemistry - how do you test for myelobasts?

A

Sudan Black B

265
Q

Cytochemistry - how do you test for Hairy cell leukaemia

A

Tartrate resistant acid phosphatase

266
Q

Cytochemistry - what does decreased leukocyte alkaline phosphatase show

A

CML, PNH

267
Q

Cytochemistry - how do you test for increased leukocyte alkaline phosphatase show?

A

PV, ET, MF

268
Q

Deep vein thrombosis

A 
Risk factors
 - increased risk with advancing age
obesity
family history of VTE
pregnancy (especially puerperium)
immobility
hospitalisation
anaesthesia
central venous catheter: femoral >> subclavian
Underlying conditions 
- malignancy
thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency
heart failure
antiphospholipid syndrome
Behcet's
polycythaemia
nephrotic syndrome
sickle cell disease
paroxysmal nocturnal haemoglobinuria
hyperviscosity syndrome
homocystinuria

Medication
-combined oral contraceptive pill: 3rd generation more than 2nd generation
hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations compared to those taking oestrogen only preparations
raloxifene and tamoxifen
antipsychotics (especially olanzapine) have recently been shown to be a risk factor

If a patient is suspected of having a DVT a two-level DVT Well’s Score should be performed.

  • If active cancer, paralyssis, paresis, recently bedridden for 3 days, loclised tenderness along DVT system, entire leg swollen, calf swelling at least 3 cm larger than asymptomatic side. Oedema, previous DVT, alternative diagnosis.

2 or more = DVT likely

If a DVT is ‘likely’ (2 points or more)
a proximal leg vein ultrasound scan should be carried out within 4 hours and, if the result is negative, a D-dimer test

if a proximal leg vein ultrasound scan cannot be carried out within 4 hours a D-dimer test should be performed and low-molecular weight heparin administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)

If a DVT is ‘unlikely’ (1 point or less)
perform a D-dimer test and if it is positive arrange:
a proximal leg vein ultrasound scan within 4 hours
if a proximal leg vein ultrasound scan cannot be carried out within 4 hours low-molecular weight heparin should be administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)

Low molecular weight heparin (LMWH) or fondaparinux should be given initially after a DVT is diagnosed.
a vitamin K antagonist (i.e. warfarin) should be given within 24 hours of the diagnosis
the LMWH or fondaparinux should be continued for at least 5 days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours, whichever is longer, i.e. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range
warfarin should be continued for at least 3 months. At 3 months, NICE advise that clinicians should ‘assess the risks and benefits of extending treatment’

unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding’. In practice most clinicians give 6 months of warfarin for patients with an unprovoked DVT/PE.

May require investigation to determine the cause in unprovoked.

For active cancer give 6 months.

269
Q

NOAC - Dabigatran

A

Direct thrombin inhibitor
Oral
Excreted renally.

Given as prevention of VTE following hip/knee surgery.

Treatment for DVT and PE.

Prevention of stroke in non-valvular AF.

Reverse Dabigatran with Idarucizumab.

270
Q

Heparin reversal?

A

Protamine

271
Q

Rivaroxaban/ Apixaban (excreted faecally).

A

Direct factor Xa inhibitor

Given as prevention of VTE following hip/knee surgery.

Treatment for DVT and PE.

Prevention of stroke in non-valvular AF.

Reverse Dabigatran with Idarucizumab.

272
Q

Filgrastim

A

G-CSF factor used to treat neutropenia in select case.

Not needed in all types of chemo and is not routinely used unless there is specific reason why. Eg.
Elderly, specific malignancy (NHL, ALL), those receiving chemo and radiation therapy.

If neutropenia is presence, increased risk of infection then more severe neutropenic sepsis.

Fluroquinolones used as antibiotic prophylaxis.

273
Q

Post thrombotic syndrome

A

Due to post-thrombotic syndrome, for which compression stocking are the recommended treatment. Keg elevation is also recommended but would not be the first choice treatment over compression stockings.

It is increasingly recognised that patients may develop complications following a DVT. Venous outflow obstruction and venous insufficiency results in chronic venous HTN.

  • Painful, heavy calves
  • Pruritus
  • Swelling
  • Varicose veins
  • Venous ulceration.

Do not offer them to prevent post-thrombotic syndrome, but offer for management of leg symptoms after DVT.

274
Q

Patient presents with asymptomatic microcytic anaemia?

A

Anti-TTG for coeliacs.

Coeliacs affect the duodenum where iron is absorbed not the jejunem.

275
Q

Chloramphenicol should be avoided in which patients/

A

Those with concurrent bone marrow suppression drugs (especially methotrexate).

Should also avoid co-trimoxazole and trimethoprim due to increased risk of methotrexate toxicity and potential pancytopenia.

276
Q

Blood transfusion threshold?

A

Patient without ACS
- 70g/L

Target after transfusion = 70-90

Patient with ACS
- 80g/L is threshold

Aim for 80-100.

277
Q

Platelet threshold for transfusion

A

Maximum <100 x 10^9 for patients with severe bleeding, bleeding at critical sites, such as CNS.

<30 is threshold for patients with more moderate clinically significant bleeding. E.g Haematemesis. Would need a platelet transfusion.

Pre-invasive procedures

  • Platelet transfusion for thrombocytopenia before surgery/an invasive procedure
  • > 50 for most patients
  • 50-75 if high risk of bleeding
  • > 100 if surgery at critical site

Do not perform platelet transfusion

  • Autoimmune thrombocytopenia
  • Chronic bone marrow failure
  • heparin-induced thrombocytopenia
  • Thrombotic thrombocytopenic purpura.
278
Q

Lymphatic drainage to the superficial inguinal lymph nodes

A 
Anal canal below pectinate line
Perineum
Skin of the thigh
Penis
Scrotum
Vagina
279
Q

Deep inguinal lymph nodes

A

Glans penis

280
Q

Para-aortic lymph nodes

A

Testes, ovaries
Kidney
Adrenal gland

281
Q

Axillary lymph nodes

A

Lateral breast

Upper limb

282
Q

Internal iliac lymph nodes

A

Anal canal above pectinate line
Lower part of rectum
Pelvic structures, including cervix and inferior part of uterus

283
Q

Superior mesenteric lymph nodes

A

Duodenum

Jejunum

284
Q

Inferior mesenteric lymph nodes

A

Descending colon
Sigmoid colon
Upper part of rectum

285
Q

Coeliac lymph nodes

A

Stomach

286
Q

Lead poisoning

A

Along with acute intermittent porphyria, lead poisoning should be considered in questions giving a combination of abdominal pain and neurological signs. Lead poisoning results in defective ferrochelatase and ALA dehydratase function.

Features
abdominal pain
peripheral neuropathy (mainly motor)
fatigue
constipation
blue lines on gum margin (only 20% of adult patients, very rare in children)

Investigations
the blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant
full blood count: microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology
raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria
urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)
in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Management - various chelating agents are currently used:
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
287
Q

IDA + B12 deficiency

A

Crohns causes a B12 deficiency due to terminal ileal disease.
If there is also chronic blood loss this may co-present with IDA.

Increased RCW shows existance of both macro and microcytic RBC which average out to a normocytic NCV.

288
Q

Post-operative anaemia

A

Consider a few days after surgery but do remember risk of PE too.

289
Q

Multiple sinusitis and recurrent infections

A

Neutrophil disorders
- Chronic granulomatous disease

Causes recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (e.g. Staphylococcus aureus and fungi (e.g. Aspergillus)
Negative nitroblue-tetrazolium test
Abnormal dihydrorhodamine flow cytometry test

  • Chediak-Higashi syndrome

Affected children have ‘partial albinism’ and peripheral neuropathy. Recurrent bacterial infections are seen
Giant granules in neutrophils and platelets

  • Leukocyte adhesion deficiency

Recurrent bacterial infections.
Delay in umbilical cord sloughing may be seen
Absence of neutrophils/pus at sites of infection

290
Q

B cell immunodeficiency

A
  • Common variable immunodeficiency

Hypogammaglobulinemia is seen. May predispose to autoimmune disorders and lymphoma

  • Bruton’s (x-linked) congenital agammaglobulinaemia

X-linked recessive. Recurrent bacterial infections are seen
Absence of B-cells with reduced immunoglogulins of all classes

  • Selective immunoglobulin A deficiency

Most common primary antibody deficiency. Recurrent sinus and respiratory infections

Associated with coeliac disease and may cause false negative coeliac antibody screen

Severe reactions to blood transfusions may occur (anti-IgA antibodies → analphylaxis)

291
Q

T cell disorders?

A

DiGeorge syndrome - Common features include congenital heart disease (e.g. tetralogy of Fallot), learning difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate

292
Q

Combined B and T cell disorders

A

Severe combined immunodeficiency -

Recurrent infections due to viruses, bacteria and fungi.
Reduced T-cell receptor excision circles
Stem cell transplantation may be successful

Hyper IgM Syndromes

nfection/Pneumocystis pneumonia, hepatitis, diarrhoea

293
Q

48 yr old man with DVT unprovoked

A

NICe recommended doing chest-x ray and urine tests to exclude underlying malignancy. CT abdo and pelvis should be arranged if normal as patient is >40. Also recommend checking anti-phospholipid antibodies for first unprovoked DVT/PE.

294
Q

Furosemide and blood?

A

If giving 2 units, give 1 unit, furosemide then the other unit.

295
Q

What is CMV negative blood products

A

CMV transmitted in leucocytes. Most blood products are now leucocyte depleted CMV negative products are rarely required.

Irradiated blood products are used to avoid transfusion GvHD caused by engraftment of viable donor T lymphocytes.

Irradiated used for granulocyte transfusion, IU transfusion, neonates up to 28 days post delivery. For bone marrow transplants, immunocompromised or patients with previous Hodgkin’s disease.

296
Q

Transfusion of packed red cells

A

Shown to increased serum potassium levels.

Non-urgent RBC usually transfused over 90-120 mins.

297
Q

Causes of vitamin B12 deficiency?

A
  • pernicious anaemia: most common cause
  • post gastrectomy
  • vegan diet or a poor diet
  • disorders of terminal ileum (site of absorption): Crohn’s,blind-loop etc
  • metformin (rare)
298
Q

Features of B12

A

macrocytic anaemia
sore tongue and mouth
neurological symptoms: e.g. ataxia
neuropsychiatric symptoms: e.g. mood disturbances

299
Q

Management of B12

A

if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months
if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

300
Q

Alcoholic man blood test?

A

Macrocytic anaemia and thrombocytopaenia.
- This is due to the portal hypertension and thrombopoetin deficiency.

Splenomegaly means larger surface area for splenic sequestration of thrombocytes. More platelets get filtered, fewer platelets in blood.

Damaged livers produce less thrombopoeitin, therefore fewer megakaryocytes are produced.

301
Q

Transexaminc acid (opposite of tPA)

A

Tranexamic acid is given as an IV bolus followed by an infusion in cases of major haemorrhage.

In the case of haemorrhage, tranexamic acid should be given as an IV bolus of 1g followed by a further 1g given as a slow infusion over 8h.

Antifibrinolytic and is given in major haemorrhage to reduce blood loss.

Primary mode of action is that it reversibly binds to lysin on plasminogen or plasmin. This prevents plasmin from binding to an degrading fibrin.

Treated commonly for menorrhagia.

Medicine Finals - Imperial & Quick Medical Revision (29 decks)

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