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


Dr Ida Martinelli, Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital, Via Pace, 9, 20122 Milano, Italy. E-mail:


Factor V Leiden and the G20210A mutation in the prothrombin gene are the most frequent abnormalities associated with venous thromboembolism. It is unknown whether the risks due to the presence of either mutation are of the same magnitude. We compared the prevalence and incidence rate of venous thromboembolism in relatives with either mutation or both. The finding of different rates might influence the strategies for primary prevention of thrombosis in carriers of these mutations. The study population included 1076 relatives of probands with the prothrombin gene mutation, factor V Leiden or both 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 prothrombin 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 thrombosis 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 risk of thrombosis was two times higher in carriers of the prothrombin gene mutation, three times higher in those with factor V Leiden and six times higher in double carriers than in non-carriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation is slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it is two or three times higher. These findings suggest that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations.