Genetic hypofibrinolysis in complicated pregnancies

Objective: To assess the hypofibrinolytic 4G/4G mutation of the plasminogen activator inhibitor (PAI-1) gene as a possible factor contributing to seve re preeclampsia, abruptio placentae, fetal growth restriction, and stillbir th. Methods: We compared 94 women from a previous report who had obstetric comp lications to 95 controls with normal pregnancies matched for ethnic backgro und and age. We collected blood and extracted DNA after delivery. All subje cts had been tested for thrombophilic mutations factor V Leiden, C677T muta tion in the methylenetetrahydrofolate reductase gene, and the G20210A mutat ion in the prothrombin gene. In the present study we tested for the hypofib rinolytic 4G/4G mutation in the PAI-1 gene. Results: Women who had obstetric complications were more likely than contro ls to be 4G/4G homozygotes, 32% (30 of 94) women versus 19% (18 of 95) cont rols, odds ratio (OR) and 95% confidence interirals (CI) 2.0 (1.02, 3.9). M utations in the PAI-1 gene were independently associated with obstetric com plications (OR 1.56, 95% CI 1.005, 2.43). Heterozygosity for the factor V L eiden mutation was more common in the 30 women who had PAI-14G/4G than in t he 18 4G/4G controls (33% versus 0%, Fisher P = .008). Seventy-six percent of women had some form of thrombophilia or hypofibrinolysis compared with 3 7% of controls (Fisher P < .001). Conclusions: Women with severe preeclampsia, abruptio placentae, fetal grow th restriction, and stillbirth had increased incidence of the hypofibrinoly tic 4G/4G mutation of the PAI-1 gene that is frequently associated with the thrombophilic factor V Leiden mutation, further predisposing them to throm bosis. (Obstet Gynecol 2001;97:44-8. (C) 2001 by The American College of Ob stetricians and Gynecologists.)