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.