Bleeding in women with venous thromboembolism during pregnancy: A systematic review of the literature

OBJECTIVES: Venous thromboembolism (VTE) represents an important cause of maternal morbidity and mortality. Estimates of bleeding associated with therapeutic‐dose anticoagulation are variable. We describe the frequency of bleeding in pregnant women receiving therapeutic anticoagulation for VTE by means of a systematic review of the literature. DATA SOURCES: Medical Literature Analysis and Retrieval System, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched. Databases were searched from inception to February 27, 2022. There was no language or geographic location restriction. METHODS OF STUDY SELECTION: The search yielded 2773 articles with 2212 unique citations. Studies were included if they described pregnant women treated for an acute VTE with therapeutic‐dose anticoagulation and a defined bleeding outcome was reported. TABULATION, INTEGRATION, AND RESULTS: Five studies met inclusion criteria. Included studies were judged to have a serious to critical risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention tool. The rate of bleeding, as defined by respective studies, ranged between 2.9% and 30.0%. Two studies included control groups, one of which found no significant difference in the risk of bleeding between groups, while the other found a significantly increased bleeding risk associated with therapeutic anticoagulation. CONCLUSION: Among pregnant women anticoagulated for VTE, the reported bleeding risk is variable. The ability to draw definite conclusions is limited by the scarcity and low quality of the studies, the small number of included patients, and the heterogeneity of bleeding definitions used. Large‐scale studies with standardized bleeding definitions are required to provide acute bleeding estimates and optimize the care of these patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021276771.