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.)
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
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). It is present in 20 to 60% (depending on patient selection) of patients with "spontaneous" venous thrombosis (2).
General references
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
Anticoagulation
1).
Treatment reference
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
