Prior preterm preeclampsia and hemostatic balance in the non-pregnant state

Objective

To evaluate whether a history of preterm preeclampsia (PreP) is associated with abnormal hemostatic features during the non-pregnant state, relative to people without a history of preeclampsia.

Study design

We conducted a retrospective sub-analysis of three prospective IRB approved studies in which individuals were evaluated outside of pregnancy during the follicular phase of their menstrual cycles. We compared parameters between subjects with prior PreP (n = 21) with a combined cohort (NL, n = 74) of healthy nulliparous subjects (n = 57) and subjects with a prior normotensive pregnancy (n = 17). T-tests were employed with P < 0.05 accepted for significance.

Main outcome measures

Levels of eight coagulation factors, protein C (PC), and thrombin generation (TG) were assessed in the presence or absence of thrombomodulin (TM) to evaluate the activation of the anticoagulant PC pathway. Results: There were no differences in TG or factor composition between healthy nulliparous and healthy primiparous people. In contrast, the PreP cohort had increased levels of factors II, V, VII, IX, X, XI, and PC compared to the NL cohort without this history. In dynamic assays examining TG in the presence of TM, the PreP group had reduced rates (nM/min) of formation and diminished peak levels when compared to the NL group.

Conclusions

Increased procoagulant factor levels are typically associated with increased TG, suggesting here that individuals with prior PreP would have a procoagulant shift in the non-pregnant state. However, the observed concurrent increase in anticoagulant PC linked with a decrease in dynamic TG suggests a possible compensatory mechanism to maintain hemostatic balance.