Inherited Thrombophilia due to Factor V Leiden Mutation

Inherited thrombophilia due to activated protein C resistance is now recognized as one of the major genetic risk factors in the development of venous thromboembolic disease. Activated protein C resistance is secondary to a point mutation in the factor V gene, factor V Leiden. The high prevalence of this mutation in the general population, mainly in Caucasians of European descent, is a major contributing factor to the high incidence of venous thromboembolic disease in the United States, affecting one in 1000 individuals annually. Heterozygosity and homozygosity for factor V Leiden increase the risk for thrombosis 5- to 10-fold and 50- to 100-fold, respectively, compared with genotypically normal individuals. Factor V Leiden is more common than all other known genetic risk factors for thrombosis, and its presence results in a compounded risk in patients with simultaneous inherited abnormalities such as protein C, protein S, antithrombin III deficiencies, hyperhomocysteinemia, and/or acquired risk factors. Therefore, detection of activated protein C resistance and genotyping for factor V Leiden are important for establishing risk for thrombosis and ultimately for patient management.