Mutations of factor V make it resistant to its normal inactivation by activated protein C and 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 (see Overview of Thrombotic Disorders). 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 is present in about 5% of European populations, 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's plasma PTT to become prolonged in the presence of snake venom–activated patient protein C) and on molecular analysis of the factor V gene.
Anticoagulation with parenteral heparin or low molecular weight heparin, followed by oral warfarin, is used for venous thrombosis, or for prophylaxis for patients at increased thrombotic risk (eg, by immobilization, severe injury, surgery). It is not known whether the newer oral anticoagulants that inhibit either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of warfarin for this disorder.
Last full review/revision October 2014 by Joel L. Moake, MD
Content last modified October 2014