Venous Thromboembolism in Heterozygotes for Factor V Leiden—The Second-Hit Hypothesis: A Report of Two Patients and a Review of the English-Language Literature

Abstract

Resistance to activated protein C (factor V Leiden, FV-R506Q) is the most prevalent inherited hypercoagulable state with a frequency of 4.5% in the American population, but 70% of heterozygotes do not experience venous thromboembolic disease. Heterozygosity for FV-R506Q will coexist in patients with deficiencies of protein S (26.1 %), protein C (14.9%), antithrombin III (15.1%), homocystinuria/ hyperhomocysteinemia (29.6%), pregnancy or postpartum (27.9%), oral contraceptives (27.5%), trauma and surgery (18.6%), and lupus anticoagulant and/or antiphospholipid antibodies (40%). The second-hit hypothesis proposes that heterozygotes for factor V Leiden mutation who do experience venous thrombosis will have a second hypercoagulable state either hereditary or acquired. Key Words: Thromboembolism—Factor V Leiden—Heterozygotes.

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