(See also Overview of Thrombotic Disorders.)
Activated protein C (APC), in complex with protein S, degrades coagulation factors Va and VIIIa, thus inhibiting coagulation (see figure Pathways in blood 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 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: if factor V Leiden is present, the patient's plasma dilute Russell's viper venom time (dRVVT), which is dependent on normal functional factor X and factor V, does not become prolonged in the presence of snake venom–activated patient protein C
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 probable, but not yet certain, that the direct oral anticoagulant (DOAC) inhibitors of either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of warfarin for this disorder.