Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.

Background: Venous thromboembolism is a leading cause of morbidity and mort ality during pregnancy and the puerperium. However, the role of mutations i n the prothrombin and factor V genes and other thrombophilic abnormalities as risk factors for thromboembolism in women during pregnancy and the puerp erium is not known. Methods: In a study of 119 women with a history of venous thromboembolism d uring pregnancy and the puerperium and 233 age-matched normal women, we mea sured the activity of antithrombin, protein C, protein S, and lupus anticoa gulant. We also performed genetic analyses to detect the G1691A mutation in the factor V gene (factor V Leiden), the G20210A mutation in the prothromb in gene, and the C677T mutation in the methylenetetrahydrofolate reductase gene. Blood samples were obtained at least three months post partum or afte r the cessation of lactation. Results: Among the women with a history of venous thromboembolism, the prev alence of factor V Leiden was 43.7 percent, as compared with 7.7 percent am ong the normal women (relative risk of venous thromboembolism, 9.3; 95 perc ent confidence interval, 5.1 to 16.9); that of the G20210A prothrombin-gene mutation, 16.9 percent as compared with 1.3 percent (relative risk, 15.2; 95 percent confidence interval, 4.2 to 52.6); and that of both factor V Lei den and the G20210A prothrombin-gene mutation, 9.3 percent as compared with 0 (estimated odds ratio, 107). Assuming an overall risk of 1 in 1500 pregn ancies, the risk of thrombosis among carriers of factor V Leiden was 0.2 pe rcent, among carriers of the G20210A prothrombin-gene mutation, 0.5 percent , and among carriers of both defects, 4.6 percent, as calculated in a multi variate analysis. Conclusions: The G20210A prothrombin-gene mutation and factor V Leiden indi vidually are associated with an increased risk of venous thromboembolism du ring pregnancy and the puerperium, and the risk among women with both mutat ions is disproportionately higher than that among women with only one mutat ion. (N Engl J Med 2000;342:374-80.) (C)2000, Massachusetts Medical Society .