Genetic thrombophilia has pleiotropic effects in pregnancy

Genetic thrombophilia has been established as a risk factor for pregnancy-associated disorders, such as thrombosis, early and late miscarriage, and pre-eclampsia. Associations between the factor V (F5) Leiden G1691A and the prothrombin/factor II (F2) G20210A SNPs and pre-eclampsia have been evaluated in over 50 association studies. A pooled analysis of 23 and 11 studies demonstrates that carriage of the F5 Leiden G1691A (p < 0.001; odds ratio [OR] 2.0; 95% confidence interval [CI] 1.6-2.5) and the F2 G20210A (p < 0.001; OR 1.8; 95% CI 1.1-2.9) SNPs is significantly associated with pre-eclampsia. Besides pre-eclampsia, genotyping for the F5 Leiden G1691A and the F2 G20210A SNPs is also useful for individual risk assessment regarding pregnancy-associated thrombosis. Carriers of the F5 Leiden G1691A SNP will develop this condition in 6.4% of heterozygotes and in 8.9-16.7% of homozygotes. A total of 6.2% of women with the F2 G20210A SNP and 17.8% of women with simultaneous carriage of the F5 Leiden G1691A and F2 G20210A SNPs will develop pregnancy-associated thrombosis. Both the F5 Leiden G1691A and F2 G20210A SNPs are also risk factors of early recurrent, late recurrent and late spontaneous miscarriage based on a published meta-analysis of 31 studies. These women may benefit from prophylactic heparinization. Six case-control and cohort studies of 687 women with genetic thrombophilia document live birth rates of 82% (181/221) using low-molecular-weight heparin or fractionated heparin compared with 20% (95/466) without therapy (p < 0.001, OR 17.7; 95% CI 12.2-25.5). Based on the data in the literature, including association studies and meta-analyses of these association studies, it can be concluded that genetic thrombophilia due to carriage of the F5 Leiden G1691A and F2 G20210A SNPs is a significant and clinically relevant risk factor for pre-eclampsia, pregnancy-associated thrombosis, and early and late miscarriages.