Thrombophilia

Question 1

What is thrombophilia?

Answer 1

Inherited/acquired coagulopathy that predisposes to thrombosis, usually venous (DVT/PE).

Question 2

What is this describing?
Chief cause of inherited thrombophilia (5% of population), single point mutation in factor V making it resistant to breakdown by APC.

Answer 2

Activated protein C resistance/factor V Leiden

Question 3

What is this describing?
Inherited thrombophilia, high prothrombin levels and increase in thrombosis due to down regulation of fibrinolysis by thrombin activated fibrinolysis inhibitor.

Answer 3

Prothrombin gene mutation

Question 4

What is this describing?
Inherited thrombophilia. Vitamin K dependent factors neutralise factor V and VIII. Heterozygous = increase risk of thrombosis. Homozygous deficiency = neonatal purpura fulminans, fatal if untreated.

Answer 4

Protein C and S deficiency

Question 5

What is this describing?

Inherited thrombophilia. Co-factors of heparin and inhibits thrombin. Homozygous is incompatible with life.

Answer 5

Antithrombin deficiency

Question 6

What are the acquired causes of thrombophilia?

Answer 6

1. Antiphospholipid syndrome
2. COCP/HRT
3. Any cause of thrombocytosis or polycythaemia

Question 7

How should you investigate suspected thrombophilia?

Answer 7

1. Patient should be well, not pregnant, and off anticoagulation of 1 month.
2. FBC, clotting (PT, TT, aPTT, fibrinogen), APC resistance test, lupus anticoagulant, anticardiolipin antibodies, assay for antithrombin and protein C & S deficiency.
3. DNA analysis by PCR for factor V Leiden if APC resistance test is +ve.

Question 8

Which patients should be investigated for thrombophilia?

Answer 8

1. Arterial thrombosis or MI <50yrs
2. Unprovoked VTA (<40yrs with no risk factors)
3. VTE with COCP/pregnancy
4. Unexplained recurrent VTE
5. Recurrent foetal loss (3 or more)
6. Neonatal thrombosis

Question 9

What is the treatment for thrombophilia?

Answer 9

1. Anticoagulate acute thrombosis
2. If recurrence occurs with no risk factors, consider lifelong anticoagulation.
3. Prophylaxis may be needed in pregnancy with heparin as warfarin is teratogenic.