Haematology

Question 1

Interpret basic coagulation tests.

Answer 1

Prolonged aPTT
- Deficiencies in intrinsic pathway (factor VIII, IX, XI, XII)
- Or inhibitors: autoantibody against factor VIII or antibodies against protein-phospholipid complexes (lupus anticoagulant)
- Factor VIII: Haemophilia A
- Factor IX: Haemophilia B
- Factor XI: Haemophilia C

Prolonged PT
- Deficiency in extrinsic pathway (factor VII)

Prolonged PT/aPTT (common pathway) with normal PLT
- Factors V, X, thrombin and fibrinogen deficiency
- Liver disease, vit K deficiency, warfarin, heparin, DOAC (thrombin/factor Xa inhibitors)

Prolonged PT/aPTT with low PLT
- DIVC
- Liver disease with portal HTN (splenic sequestration)

Thrombin clotting time (TCT)
- Measure of final step in coagulation cascade: conversion of fibrinogen to fibrin via thrombin action
- Deficiencies in fibrinogen or drugs such as direct or indirect thrombin inhibitors

Question 2

What are the major regulators of coagulation (terminate coagulation)?

Answer 2

• Heparin sulphate: binds to antithrombin, increases its action, inactivates thrombin and factor Xa
• Tissue factor pathway inhibitor: inactivates extrinsic pathway
• Thrombomodulin: binds to thrombin and activates protein C (protein S is co-factor), inactivates factor Va

Question 3

Interpretation of mixing test.

Answer 3

• Done when there is isolated aPTT prolongation
• To look for factor deficiency vs presence of inhibitors
• Normal plasma (with normal coag factors) is mixed with patient plasma
• If aPTT corrects: factor VIII, IX deficiency
• If aPTT does not correct: presence of inhibitors (factor VIII autoantibody, or protein-phospholipid complexes antibody)

Question 4

What is the role of vitamin K in the coagulation pathway?

Answer 4

Cofactor to activate factors II, VII, IX, X

Question 5

What are the causes of pancytopaenia?

Answer 5

1. Impaired production (marrow failure or infiltration disorders)
   - Aplastic anaemia, acquired or congenital (congenital far less common, even in children)
   - Primary/autoimmune myelofibrosis
   - Myelodysplastic syndrome
   - Granulomatous disease
   - Malignancy
   - Metabolic
   - Nutritional: B12, folate, copper, alcohol
   - Viral infections: Hep B, Hep C, HIV, CMV, EBV, HHV-6, parvovirus B19
2. Peripheral destruction
   - Autoimmune haemolytic pancytopaenia
   - Splenic sequestration
3. Mixed impaired production and peripheral destruction
   - Paroxysmal nocturnal haemoglobinuria
   - SLE
   - Drugs
   - HLH
   - Leukaemia
   - Transfusion-associated graft vs host disease