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20 April 1999 | Volume 130 Issue 8 | Pages 643-650
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.
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 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.
Author and Article Information
From S. Bortolo Hospital, Vicenza, Italy.
Acknowledgments: The authors thank Dr. M. Frezzato and Dr. S. Dal Santo for clinical work; Drs. E. Missiaglia, A. Cocco, E. Gatto for laboratory and molecular biology investigations; Drs. E. Boscaro, R. Trombini, and D. Zenere for clinical data collection; and the secretaries, nurses, and laboratory technicians. They also thank all of the family doctors of Vicenza for their enthusiastic collaboration.
Grant Support: By Associazione per la Lotta alla Trombosi, Milan, Italy, and Associazione Vicentina per l'Emofilia e le Coagulopatie and Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno ed Ancona, Italy.
Requests for Reprints: Francesco Rodeghiero, MD, Hematology Department, S. Bortolo Hospital, 36100 Vicenza, Italy.
Current Author Addresses: Drs. Rodeghiero and Tosetto: Hematology Department, S. Bortolo Hospital, 36100 Vicenza, Italy. ARTICLE
Activated Protein C Resistance and Factor V Leiden Mutation Are Independent Risk Factors for Venous Thromboembolism
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