About this condition
Factor V Leiden / Thrombophilia
Factor V Leiden is the most common inherited thrombophilia in individuals of European descent. It results from a single mutation in the F5 gene (c.1601G>A) that renders Factor V resistant to inactivation by activated protein C, shifting the hemostatic balance toward clot formation. Prothrombin thrombophilia, caused by a variant in the F2 gene (20210G>A), elevates prothrombin levels and similarly increases clotting risk. Both follow autosomal dominant inheritance with incomplete penetrance — many carriers never develop thrombosis without additional trigger factors.
Factor V Leiden affects 3–8% of individuals of European ancestry, with much lower prevalence in African and Asian populations. Heterozygotes have a 3–8-fold increased lifetime risk of deep vein thrombosis (DVT) or pulmonary embolism (PE); homozygotes have approximately 80-fold increased risk. Prothrombin 20210G>A occurs in 2–5% of European populations and confers a 2–5-fold increased VTE risk in heterozygotes. Risk is substantially amplified by additional factors: oral contraceptive use raises DVT risk to 35-fold in FVL heterozygotes, and combined heterozygosity for both F5 and F2 variants further compounds risk.
Identifying a thrombophilia variant has major clinical implications. For women, it informs contraceptive choice — combined hormonal contraceptives are contraindicated, while alternative options such as intrauterine devices or progestin-only methods are preferred. For surgery, it guides perioperative anticoagulation strategies. During pregnancy, heterozygous carriers have moderately increased VTE risk (1–2%), while homozygotes require pharmacological thromboprophylaxis. A finding in one family member triggers cascade testing of relatives, identifying at-risk individuals before a first thrombotic event.
Factor V Leiden and prothrombin 20210G>A represent distinct genetic mechanisms — APC resistance vs. elevated prothrombin — but confer similar clinical VTE risk; compound heterozygosity significantly increases risk.
- Gene locus
- F5 (1q24.2), F2 (11p11.2)
