The risk of venous thromboembolism in family members with mutations in thegenes of factor V or prothrombin or both

Factor V Leiden and the G20210A mutation in the prothrombin gene are the mo st frequent abnormalities associated with venous thromboembolism. It is unk nown whether the risks due to the presence of either mutation are of the sa me magnitude. We compared the prevalence and incidence rate of venous throm boembolism in relatives with either mutation or both. The finding of differ ent rates might influence the strategies for primary prevention of thrombos is in carriers of these mutations. The study population included 1076 relat ives of probands with the prothrombin gene mutation, factor V Leiden or bot h who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were non-carriers. The prevalence of venous thromboembolism was 5.7% in relatives with the pro thrombin gene mutation, 7.8% in those with factor V Leiden, 17.1% in those with both mutations and 2.5% in non-carriers. Annual incidences of thrombos is were 0.13% [95% confidence interval (CI) 0.06-0.24], 0.19% (0.13-0.25), 0.42% (0.15-0.83) and 0.066% (0.03-0.11), respectively, and the relative ri sk of thrombosis was two times higher in carriers of the prothrombin gene m utation, three times higher in those with factor V Leiden and six times hig her in double carriers than in non-carriers. The incidence of venous thromb oembolism in carriers of the prothrombin gene mutation is slightly lower th an that observed in carriers of factor V Leiden, whereas in carriers of bot h mutations it is two or three times higher. These findings suggest that li felong primary anticoagulant prophylaxis of venous thromboembolism is not n eeded in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thr ombosis coexist with mutations.