(See also Overview of Thrombotic Disorders Overview of Thrombotic Disorders In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more .)
Activated protein C (APC), in complex with protein S, degrades coagulation factors Va and VIIIa, thus inhibiting coagulation (see figure ). 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
Factor V Leiden as a single gene defect is present in about 5% of White Americans, but it rarely occurs in native Asian or African populations (1 General references Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. (See also Overview of Thrombotic Disorders... read more ). It is present in 20 to 60% (depending on patient selection) of patients with "spontaneous" venous thrombosis (2 General references Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. (See also Overview of Thrombotic Disorders... read more ).
1. Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997;277(16):1305-1307.
2. Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med 2002;162(20):2357-2360. doi:10.1001/archinte.162.20.2357
Diagnosis of Factor V Resistance to APC
Plasma coagulation assay
Diagnosis is based on
The activated protein C resistance assay
Genetic mutation analysis of the factor V gene using DNA-based assays
The activated protein C resistance assay is a screening test for the presence of factor V Leiden. Activated protein C is added to a 5-fold dilution of patient plasma, and the coagulation time is measured. In patients with homozygous or heterozygous factor V Leiden resistance , the prolongation of the clotting time is significantly reduced because their factor V is resistant to cleavage by activated protein C.
Confirmation of factor V Leiden is then done by DNA-based testing for the mutation.
Treatment of Factor V Resistance to APC
Direct oral anticoagulants are at least as effective as warfarin for the treatment of venous thromboembolism in patients with thrombophilia including factor V Leiden (1 Treatment reference Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. (See also Overview of Thrombotic Disorders... read more ).
1. Campello E, Spiezia L, Simion C, et al. Direct Oral Anticoagulants in Patients With Inherited Thrombophilia and Venous Thromboembolism: A Prospective Cohort Study. J Am Heart Assoc 2020;9(23):e018917. doi:10.1161/JAHA.120.018917
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