Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy

Objective To investigate coagulation inhibitors and abnormalities of the ho mocysteine metabolism, which are related to an increased thrombotic risk, a s risk factors for placental vasculopathy. Design A case-control study comparing nonpregnant women with an obstetric h istory of placental vasculopathy (study group) with nonpregnant women (cont rol group) matched for age and occupation. Setting Obstetric outpatient clinic in the University Hospital Nijmegen. Sample One hundred and one women in the study group and 92 women in a contr ol group. Methods Determinations in blood samples of homocysteine concentrations; the occurrence of 677 C-->T mutation in the methylenetetrahydrofolate reductas e (MTHFR) gene; protein C activities; activated protein C resistance ratios ; concentrations of free protein S antigen; antithrombin III activities; an d the occurrence of factor V Leiden mutation. Results Increased risk for placental vasculopathy was found in the study gr oup with elevated homocysteine (odds ratio 2.28, 95% CI 1.18-4.39), MTHFR m utation (odds ratio 3.29, 95% CI 1.03-10.5), decreased activated protein C resistance ratio (odds ratio 2.46, 95% CI 1.06-5.72) and protein C (odds ra tio 2.01, 95% CI 1.11-3.65). Any combination of two risk factors in the sam e individual resulted in a 3.40 (95% CI 1.80-6.42) higher relative risk for placental vasculopathy; combinations of three risk factors in a 6.83 (95% CI 1.52-30.7) higher risk. Conclusions The thrombotic risk factors decreased levels of activated prote in C resistance ratios and protein C, elevated homocysteine and the MTHFR 6 77 C-->T mutation are likely risk factors for placental vasculopathy. Combi nations of these risk factors in one individual resulted in synergistic inc rease of risk.