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Factor V Resistance to Activated Protein C (APC)


Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Jan 2021| Content last modified Jan 2021

Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they predispose to venous thrombosis.

(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.

Pathways in blood coagulation

Pathways in blood coagulation

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 of Factor V Resistance to APC

  • Plasma coagulation assay

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

Treatment of Factor V Resistance to APC

  • Anticoagulation

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.

Drugs Mentioned In This Article

Drug Name Select Trade
rivaroxaban XARELTO
warfarin COUMADIN
apixaban ELIQUIS

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