The risk of bleeding in pregnant women with acute venous thromboembolism treated with anticoagulants: an international multidatabase cohort study

Abstract

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, is a major cause of maternal mortality. Low-molecular-weight heparin (LMWH) is the mainstay of therapy for VTE during pregnancy. However, the effects of different LMWH types and dosing regimens on bleeding risk remain unclear.

Objectives: To compare the risk of major bleeding among pregnant women with acute VTE treated with the most used therapeutic dose LMWH, dalteparin in Québec and enoxaparin in Germany, vs other LMWHs. We also examined the impact of once-daily vs. twice-daily LMWH dosing on bleeding outcomes.

Methods: This multinational retrospective cohort study used population-level healthcare data from Québec, Canada, and Germany and included women with acute VTE during pregnancy who initiated therapeutic doses of LMWH within 15 days of an incident VTE. We used Cox proportional hazards models to compare the risk of major bleeding associated with different LMWHs.

Results: The study cohort included 567 pregnant women (Germany: n = 308; Québec: n = 259) with VTE treated with LMWH. Major bleeding occurred in 6.5% to 7.7% of patients in both cohorts. The hazard ratios (95% CIs) for the most prescribed LMWH vs other LMWHs were 0.9 (0.3-2.5) in Québec and 1.4 (0.5-4.1) in Germany. No significant differences in bleeding risk were found between once-daily and twice-daily dosing schedules.

Conclusion: Our multinational cohort study provided population-based incidence rates for bleeding related to LMWH use during VTE treatment in pregnancy. Moreover, while hypothesis-generating, our findings suggest that the LMWH type and dosing frequency may not influence bleeding risk in pregnant women with VTE. Further research is necessary to explore anticoagulation strategies to optimize outcomes and minimize bleeding complications.

Keywords: anticoagulants; hemorrhage; pregnancy; venous thromboembolism.