Factor V (Leiden) Mutation Analysis

Laboratory assay overview

This profile examines the most common hereditary and acquired thrombophilia risk factors associated with recurrent miscarriage or stillbirth.

Laboratory assay overview

This test detects the factor V Leiden and prothrombin (factor II c.*97G>A) gene variants, the most common causes of inherited thrombophilia; it may be used to evaluate individuals with a strong personal or family history of venous thromboembolism (VTE) and inform treatment or preventive decisions [1]. Factor V Leiden refers to the c.1691G>A variant in the FV gene, which encodes coagulation factor V. This variant results in resistance to factor V protein degradation by activated protein C and increases the risk of VTE 6 to 8 fold in heterozygous carriers and 80 fold in homozygous carriers [1]. The mean age of symptom onset is 31 to 44 years, but some heterozygous carriers can be asymptomatic [2]. In the United States, Factor V Leiden is most prevalent in White individuals, with an estimated frequency of 5% [1]. The prothrombin gene variant (factor II c.*97G>A) is a variant in the F2 gene, which encodes coagulation factor II. This variant increases the risk of venous thrombosis 2 to 4 fold in heterozygous carriers [1] and 20 fold in coinherence of factor V Leiden and factor II c.*97G>A [2]. Factor II c.*97G>A is most prevalent in White Americans with an estimated frequency of 1% to 3% [1]. Factor V Leiden and factor II c.*97G>A testing may be indicated in clinical scenarios where results can help guide clinical decisions for the patient and family members. These clinical scenarios include first VTE developed under 50 years of age, VTE at an unusual site (eg, cerebral veins), recurrent VTE, a strong family history of VTE, and low activated protein C resistance activity [1]. Routine testing for factor V Leiden and factor II c.*97G>A is not recommended for prenatal carrier screening, newborn screening, or individuals taking oral contraceptive [2]. Approximately 50% to 60% of familial thrombophilia is associated with variants in the FV or F2 gene; variants in the genes that encode protein C, protein S, and antithrombin can also cause inherited thrombophilia. The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings. References 1. Zhang S, et al. Genet Med. 2018;20(12):1489-1498. 2. Vnencak-Jones CL, et al. Genetics. In: Rifai R, et al, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier Inc; 2022.