Thrombophilia

Question 1

Factor V Leiden

Answer 1

= MOST COMMON INHERITED THROMBOPHILIA

Example Question:
A 27-year-old woman is admitted after developing dyspnoea associated with pleuritic chest pain. A D-dimer taken on admission is elevated and subsequent CTPA shows a pulmonary embolism. Her past medical history includes a giving birth to her son 12 months ago (full term, vaginal delivery) and anxiety. She reports that her 47-year-old mother has had two deep vein thromboses in the past 10 years. Which one of the following is the most likely underlying cause?

	> Factor V Leiden
	Antithrombin III deficiency
	Antiphospholipid syndrome
	Protein C deficiency
	Prothrombin gene mutation

Factor V Leiden is the most common inherited thrombophilia

NICE would recommend testing for thrombophilia given the unprovoked venous thromboembolism and family history.

Question 2

Thrombophilia - Inherited Causes

Answer 2

Inherited

Gain of function polymorphisms
factor V Leiden (activated protein C resistance): most common cause of thrombophilia
prothrombin gene mutation: second most common cause

Deficiencies of naturally occurring anticoagulants
antithrombin III deficiency
protein C deficiency
protein S deficiency

Question 3

Thrombophilia - Acquired Causes

Answer 3

Acquired
Antiphospholipid syndrome

Drugs
the combined oral contraceptive pill

Question 4

Inherited Thrombphilias - Prevalence

Answer 4

Prevalence of Condition:

Factor V Leiden (heterozygous) 5%

Prothrombin gene mutation (heterozygous) 1.5%

Protein C deficiency 0.3%

Protein S deficiency 0.1%

Antithrombin III deficiency 0.02

Question 5

Inherited Thrombophilias - Risk of VTE

Answer 5

Relative risk of VTE
Factor V Leiden (heterozygous) 4

Prothrombin gene mutation (heterozygous) 3

Protein C deficiency 10

Protein S deficiency 5-10

Antithrombin III deficiency 10-20

Question 6

Antithrombin III Deficiency

Answer 6

= inherited cause of thrombophilia - occurring in approx 1: 3000 of the population

= AUTOSOMAL DOMINANT
= Heterogenous group of disorders as some patients have deficiency of normal antithrombin III and others have abnormal antithrombin III

Antithrombin III inhibits several clotting factors: Thrombin, Factors 9a, 10a, 11a and 12a
Antithrombin III also mediates effect of heparin

Features:

• recurrent venous thrombosis
• arterial thromboses do occur but uncommon

Mx:

• LIFELONG WARFARIN
• Heparinisation during pregnancy (NB as patients with antithrombin III deficiency will have a degree of resistance to heparin, anti-Xa levels should be monitored to ensure adequate anticoagulation
• Antithrombin III concentrates (often used during surgery or childbirth)

Question 7

Factor V Leiden

Answer 7

= Activated protein C resistance

• most common inherited thrombophilia
• present in 5% of population
• due to a mutation in Factor V Leiden
• heterozygous have a 4-5 fold risk of VTE
• 5% prevalence
• relative risk of VTE = 4