Abstract
Obstetrical complications such as severe preeclampsia and HELLP syndrome are associated with abnormal placental vasculature and inadequate placental maternal-fetal circulation. Hereditary risk determinants of venous thrombosis have been reported to be associated with these obstetrical complications.The magnitude of the association between thrombophilia and the obstetrical complications varies in the published studies, according to type of obstetrical complication and type of thrombophilia. No data exist so far whether these risk determinants are related to premature onset of severe preeclampsia.
We used a case-control design in 99 women with severe preeclampsia (blood pressure higher than 160/100 mm Hg; urinary protein excretion greater than 5 g per day, platelet count of less than 100.000/μl; combination of hemolysis, high serum aminotransferase concentration, and platelet count below 100.000/μl; or eclampsia) in previous pregnancies and 277 normal women to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. Moreover, a case-only design was used to assess these risk factors as risk determinants for premature severe preeclampsia. We determined the genetic risk markers factor V Leiden G1691A (FVL), the G20210A prothrombin gene mutation, the methylenetetrahydrofolate reductase polymorphism (MTHFR C677T), and the PAI A844G polymorphism. None of the women had a combined or homozygous defect of the FVL or the G20210A prothrombin gene mutation. Women with antiphospholipid syndrome were excluded. None of the women had a deficiency of antithrombin, protein C, or protein S.
Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia (FVL p=0.680, prothrombin mutation p=0.479, MTHFR 677TT genotype p=0.565, PAI 844GG genotype p=0.641). In the case-only design, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.5 weeks, p=0.04) and in women with the PAI 844GG genotype (27.2 weeks vs. 30.7, p=0.025). No such significant difference was observed in carriers of the FVL or the MTHFR 677TT genotype. Hereditary risk factors for venous thrombosis are not risk determinants for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI 844GG genotype are at risk for premature onset of severe preeclampsia. Based on our results it appears that these risk factors do not induce the pathomechanism but modulate the course of preeclampsia.
Spontaneous venous thrombosis in inflammatory bowel disease: relevance of factor V Leiden and the prothrombin gene mutation
