Mutations of factor V that make it resistant to its normal inactivation by activated protein C predispose to venous thrombosis.

Activated protein C (APC), in complex with protein S, degrades factors Va and VIIIa, thus inhibiting coagulation. Any of several mutations to factor V make it resistant to inactivation by APC, increasing the tendency for thrombosis. Factor V Leiden is the most common of these mutations. Homozygous mutations increase the risk of thrombosis more than do heterozygous mutations.

Factor V Leiden as a single gene defect in European populations is present in about 5%, but it rarely occurs in native Asian or African populations. It is present in 20 to 60% of patients with spontaneous venous thrombosis.

Diagnosis is based on a functional plasma coagulation assay (eg, the failure of patient plasma PTT to become prolonged in the presence of snake venom–activated patient protein C) and on molecular analysis of the factor V gene.

Treatment, if necessary, involves anticoagulation with parenteral heparin or low molecular weight heparin, followed by oral warfarin.

Last full review/revision January 2013 by Joel L. Moake, MD