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 (Leiden) mutation is the most common clotting abnormality in patients with venous thromboembolism.


OBJECTIVE
To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in the general population.


METHODS
Cross-sectional survey.


METHODS
General community of Vicenza, Italy.


METHODS
A population-based sample of 15,109 white persons 18 to 65 years of age who were randomly selected from the census list.


METHODS
Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investigated in all participants; 2134 participants with resistance to activated protein 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. The 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 thromboembolism, mostly after surgery. Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%.


CONCLUSIONS
The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism. Screening 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 patients with venous thromboembolism.
Rodeghiero
F
F
Hematology Department, S. Bortolo Hospital, Vicenza, Italy.
Tosetto
A
A
D020016:Activated Protein C Resistance / Q000150:complications*; D000293:Adolescent; D000328:Adult; D000368:Aged; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology* / Q000235:genetics; D020246:Venous Thrombosis / Q000209:etiology* / Q000235:genetics
D005165:Factor V