In 81 women referred for diagnosis-therapy of atherothrombotic and endocrine disorders, and found to be heterozygous (n = 49) or homozygous (n = 3) for the G1691A Factor V Leiden mutation (FV), or heterozygous (n = 29) for the G20210A prothrombin gene mutation (PTG), and having ≥ 1 pregnancy, our specific aim was to assess relationships of familial thrombophilia to previous pregnancy outcomes. The 52 women with FV (1 black, 43 white, 8 other, 47 ± 13 years old) had 164 pregnancies with 114 live births (70%) and 50 miscarriages (30%). The 29 women with PTG (1 black, 28 white, 51 ± 15 years old) had 64 pregnancies with 50 live births (83%) and 10 miscarriages (17%). In 130 normal control women referred for diagnosis-therapy of atherosclerotic and endocrine disorders, having wild-type normal FV and PTG, there were 125 pregnancies with 110 live births and 13 miscarriages (10.4%). The miscarriage rate in women with FV (30%) was 3 times higher (p<.0001) than in the 130 normal controls (10.4%). The miscarriage rate in women with PTG (17%) was not significantly (p = .24) higher than in the 130 normal controls (10.4%). Of the 52 women with FV, 38 had concurrent measurement of the hypofibrinolytic 4G4G plasminogen activator inhibitor-1 (PAI-1) mutation. In 15 (of 38) women with 4G4G homozygosity and the FV mutation, there were 22 miscarriages (44%) in 50 pregnancies; in the 23 (of 38) women with 4G5G/5G5G genotypes and the FV mutation, there were 27 miscarriages (39%) in 70 pregnancies, p = 0.6. Of the 52 women with FV, 43 had measurement of the thrombophilic C677T methylenetetrahydrofolate reductase (MTHFR) mutation. In 8 women with MTHFR homozygosity and the FV mutation, the miscarriage rate was 33% (7 of 21 pregnancies); in 35 MTHFR heterozygous/wild-type normal genotypic women and the FV mutation, the miscarriage rate was 35% (42 of 120 pregnancies), p = 0.9.Heterozygosity for the Factor FV mutation is a major risk factor for miscarriage, reversible by low molecular weight heparin thromboprophylaxis throughout pregnancy.
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