Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy.

OBJECTIVE: To investigate coagulation inhibitors and abnormalities of the homocysteine metabolism, which are related to an increased thrombotic risk, as risk factors for placental vasculopathy.
DESIGN: A case-control study comparing nonpregnant women with an obstetric history of placental vasculopathy (study group) with nonpregnant women (control 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 control group.
METHODS: Determinations in blood samples of homocysteine concentrations; the occurrence of 677 C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene; protein C activities; activated protein C resistance ratios; concentrations of free protein S antigen; antithrombin III activities; and the occurrence of factor V Leiden mutation.
RESULTS: Increased risk for placental vasculopathy was found in the study group with elevated homocysteine (odds ratio 2.28, 95% CI 1.18-4.39), MTHFR mutation (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 ratio 2.01, 95% CI 1.11-3.65). Any combination of two risk factors in the same 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 protein C resistance ratios and protein C, elevated homocysteine and the MTHFR 677 C-->T mutation are likely risk factors for placental vasculopathy. Combinations of these risk factors in one individual resulted in synergistic increase of risk.