Thromboprophylaxis in pregnancy and the puerperium

N Engl J Med. 2000 Feb 10;342(6):374-80.

Background:

Venous thromboembolism is a leading cause of morbidity and mortality during pregnancy and the puerperium. However, the role of mutations in the prothrombin and factor V genes and other thrombophilic abnormalities as risk factors for thromboembolism in women during pregnancy and the pueperium is not known.

Methods:

In a study of 119 women with a history of venous thromboembolism during pregnancy and the puerperium and 233 age-matched normal women, we measured the activity of antithrombin, protein C, protein S, and lupus anticoagulant. We also performed genetic analyses to detect the G1691A mutation in the factor V gene (factor V Leiden), the G20210A mutation in the prothrombin gene, and the C677T mutation in the methylenetetrahydrofolate reductase gene. Blood samples were obtained at least three months post partum or after the cessation of lactation.

Results:

Among the women with a history of venous thromboembolism, the prevalence of factor V Leiden was 43.7 percent, as compared with 7.7 percent among the normal women (relative risk of venous thromboembolism, 9.3; 95 percent 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 Leiden 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 pregnancies, the risk of thrombosis among carriers of factor V Leiden was 0.2 percent, among carriers of the G20210A prothrombin-gene mutation, 0.5 percent, and among carriers of both defects, 4.6 percent, as calculated in a multivariate analysis.

Conclusions:

The G20210A prothrombin-gene mutation and factor V Leiden individually are associated with an increased risk of venous thromboembolism during pregnancy and the puerperium, and the risk among women with both mutations is disproportionately higher than that among women with only one mutation.

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