FN: Thrombophilia

Question 1

Definition

Answer 1

Coagulopathy predisposing to thrombosis, usually venous.

Question 2

Inherited

Answer 2

• Factor V Leiden / APC resistance
• Prothrombin Gene Mutation
• Protein C and S Deficiency
• Antithrombin III Deficiency

Question 3

Acquired 􏰀

Answer 3

􏰀
Progesterones in OCPs
Anti-phospholipid syndrome

Question 4

Factor V Leiden / APC resistance

Answer 4

Protein C deactivates F5 and F8
􏰂 - ̄c protein S and thrombomodulin cofactors
􏰀 Degradation resistance present in 5% of population 􏰂 - Most don’t develop thrombosis
􏰀 Heterozygotes: 5x ↑VTE
􏰀 Homozygotes: 50x ↑ VTE

Question 5

Prothrombin Gene Mutation

Answer 5

↑ prothrombin levels

􏰀 ↑ thrombosis due to ↓ fibrinolysis by thrombin-activated fibrinolysis inhibitor

Question 6

Protein C and S Deficiency

Answer 6

Heterozygotes for either have ↑ risk of thrombosis. 􏰂 Skin necrosis occurs – esp. ̄c warfarin
􏰀 Heterozygotes → neonatal purpura fulminans

Question 7

Antithrombin III Deficiency

Answer 7

􏰀 AT is heparin co-factor → thrombin inhibition
􏰀 Deficiency affects 1/500
􏰀 Heterozygotes have ↑↑ thrombosis risk
􏰀 Homozygosity is incompatible ̄c life

Question 8

Anti-phospholipid syndrome description

Answer 8

CLOTs: venous and arterial
􏰄 Coagulation defect: ↑APTT
􏰄 Livido reticularis
􏰄 Obstetric complications: recurrent 1st
trimester abortion
􏰄 Thrombocyotpenia

Question 9

Thrombophilia screen indications

Answer 9

􏰀 Arterial thrombosis

Question 10

Investigations thrombophillia

Answer 10

􏰀 FBC, clotting, fibrinogen concentration
􏰀 Factor V Leiden / APC resistance
􏰀 Lupus anticoagulant and anti-cardiolipin Abs
􏰀 Assays for AT, protein C and S deficiencies
􏰀 PCR for prothrombin gene mutation

Question 11

Thrombophilia Rx

Answer 11

􏰀 Rx acute thrombosis as per normal
􏰀 Anticoagulate to INR 2-3
􏰀 Consider lifelong warfarin
􏰀 If recurrence occurs on warfarin ↑INR to 3-4

Question 12

Thrombophilia prevention􏰀

Answer 12

􏰀 Lifelong anticoagulation not needed if asymptomatic
􏰀 ↑VTErisk ̄cOCPorHRT
􏰀 Prophylaxis in high risk situations
􏰂 Surgery
􏰂 Pregnancy