The maternal hemostatic shift: Understanding VTE risk in pregnancy and postpartum

Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality, with pregnancy increasing the risk of VTE four- to five-fold compared with the non-pregnant state and up to 60-fold in the postpartum period. The incidence of pregnancy-related VTE ranges from 0.5 to 2.0 per 1000 pregnancies, with deep vein thrombosis (DVT) and pulmonary embolism (PE) accounting for most cases. The heightened thrombotic risk during pregnancy and postpartum stems from physiological adaptations in hemostasis, creating a hypercoagulable state to mitigate hemorrhage risk at delivery. These changes involve increased coagulation activation, reduced fibrinolysis, and venous stasis, fulfilling Virchow's triad. The risk rises as pregnancy progresses, peaking in the third trimester and postpartum period, with both hormonal fluctuations and mechanical factors playing key roles. Estrogen and progesterone contribute to early pregnancy risk by enhancing clotting factor synthesis, while later stages involve uterine compression of venous structures, impairing venous return. The postpartum period presents the highest risk, driven by endothelial injury during delivery, inflammatory responses, and hemodynamic shifts. Evolving obstetric practices, such as early ambulation and compression therapy, may have influenced the temporal distribution of VTE events. This review aims to clarify how pregnancy-specific hemostatic adaptations influence thrombotic risk and to identify strategies for improved, individualized prevention. Despite updated international guidelines, major discrepancies persist in risk scoring and prophylaxis thresholds, underscoring the limitations of current empirical approaches. Functional biomarkers such as thrombin generation and the Endogenous thrombin potential (ETP)-based activated protein C (APC) resistance assay, could represent promising tools to bridge the gap between mechanistic understanding and clinical application.