Gain of function polymorphisms
Deficiencies of naturally occurring anticoagulants
Antiphospholipid syndrome
Drugs
The table below shows the prevalence and relative risk of venous thromboembolism (VTE) of the different inherited thrombophilias:
| Condition | Prevalence | Relative risk of VTE |
|---|---|---|
| Factor V Leiden (heterozygous) | 5% | 4 |
| Factor V Leiden (homozygous) | 0.05% | 10 |
| Prothrombin gene mutation (heterozygous) | 1.5% | 3 |
| Protein C deficiency | 0.3% | 10 |
| Protein S deficiency | 0.1% | 5-10 |
| Antithrombin III deficiency | 0.02% | 10-20 |
Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.
It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance,
Heterozygotes have a 4-5 fold risk of venous thrombosis. Homozygotes have a 10 fold risk of venous thrombosis but the prevalence is much lower at 0.05%.
Screening for factor V Leiden is not recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.