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

Abstract

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.

Standardizing definitions for bleeding events in studies including pregnant women: A call to action

“…Anticoagulation may therefore be hypothesized to influence PPH risk by affecting the fourth “T.” As the authors point out, further challenges arise from the fact that variability in peripartum clinical practices also likely influence bleeding risks and obstetric intervention can differ widely by center, in particular the routine use of active management of the third stage of labor and the time interval between the last dose of LMWH and delivery. Further challenges arise from the way that PPH is measured and defined 10 …”

“…In this issue of RPTH, Simard and colleagues tackled this important knowledge gap. They conducted a systematic review according to a prespecified protocol registered on PROSPERO (CRD42021276771) and conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, the aim of which was to evaluate the risk of antepartum and postpartum bleeding in women receiving therapeutic anticoagulation for VTE during pregnancy 10 . Studies were included if they involved use of therapeutic anticoagulation for treatment of acute pregnancy‐associated VTE with weight‐adjusted LMWH and if they reported a defined bleeding outcome.…”

“…Further challenges arise from the way that PPH is measured and defined. 10 There has indeed been a shameful lack of a clear bleeding definition as a safety outcome in past studies evaluating LMWH during and after pregnancy. In a 2019 systematic review of RCTs addressing this issue, and including a range of LMWH doses and indications, only 34% of the 2690 women included in a trial evaluating the effect of LMWH had bleeding events prospectively recorded using a standardized definition.…”