Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism

Background: Resistance to activated protein C due to the factor V R506Q (Le iden) mutation is the most common clotting abnormality in patients with ven ous thromboembolism. Objective: To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in t he general population. Design: Cross-sectional survey. Setting: General community of Vicenza, Italy. Patients: A population-based sample of 15 109 white persons 18 to 65 years of age who were randomly selected from the census list. Measurements: Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investig ated in all participants; 2134 participants with resistance to activated pr otein C were screened for the factor V Leiden mutation. Results: Carriers of the factor V Leiden mutation had a relative risk of 3. 3 (95% CI, 1.7 to 6.1) for venous thromboembolism before 65 years of age. T he fraction of cases attributable to the factor V Leiden mutation was 6.6%. By 65 years of age, 5.7% of carriers of the mutation had had venous thromb oembolism, mostly after surgery. Participants with a reduced response to ac tivated protein C were at higher risk even if they did not carry the mutati on (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thr omboembolism was 5.1%. Conclusions: The factor V Leiden mutation and resistance to activated prote in C are important, independent risk factors for venous thromboembolism. Sc reening strategies for the factor V Leiden mutation in patients undergoing surgery or experiencing major trauma cannot be recommended, but phenotypic evaluation of resistance to activated protein C should be encouraged in pat ients with venous thromboembolism.