Key result
Different LMWH dosing regimens show similar thromboembolic and bleeding risks during pregnancy.
Why the study?
The risk of thromboembolic complications and major bleeding with weight-based, fixed, and anti-Xa-monitored dosing of LMWHs during pregnancy was uncertain.
Does anti-Xa-monitored dosing of LMWHs compared to weight-based or fixed dosing reduce thromboembolic complications and major bleeding in pregnant individuals?
Meta-Analysis
Does anti-Xa-monitored dosing of LMWHs compared to weight-based or fixed dosing reduce thromboembolic complications and major bleeding in pregnant individuals?
Current evidence shows overlapping event rates for thromboembolic complications and major bleeding across different LMWH dosing regimens in pregnancy, though the certainty of evidence is low.
Overlapping event rates across LMWH regimens do not favor any strategy in pregnancy; low-certainty meta-analysis leaves optimal dosing unresolved for trials.
BACKGROUND: Low-molecular-weight heparins (LMWHs) are widely used in pregnancy for prevention and treatment of venous thromboembolism (VTE) and in individuals with mechanical heart valves (MHVs). OBJECTIVES: Our aim was to determine the risk of thromboembolic complications (TECs) and major bleeding with weight-based, fixed, and anti-Xa-monitored dosing of LMWHs during pregnancy. METHODS: We conducted a systematic review and searched 6 databases for articles published before August 2024 that reported on LMWH dosing and monitoring during pregnancy. We calculated event rates and 95% confidence intervals (95% CIs) for maternal death, TECs, and major bleeding using a random-effects meta-analysis. We assessed risk of bias using the Quality In Prognosis Studies tool and evaluated the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We identified 5007 studies, of which 94 (53 case series, 30 cohort studies, and 11 randomized trials) were eligible. For thromboprophylaxis and VTE treatment, fixed, weight-based, and anti-Xa-monitored LMWH doses had overlapping pooled event rates and 95% CIs for TECs and major bleeding. For MHVs, the risk of maternal death, TECs, and major bleeding was 2.7% (95% CI, 0.3%-6.5%), 7.9% (95% CI, 2.8%-14.6%), and 8.4% (95% CI, 2.0%-17.2%), respectively with overlapping pooled single-arm event rates and 95% CIs across different anti-Xa-monitored LMWH dosing regimens. The CoE for all estimates was low to very low, mainly due to imprecision, risk of bias, and publication bias. CONCLUSION: Pooled single-arm event rates and 95% CIs for the main outcomes overlapped across LMWH dosing regimens currently used in pregnancy for thromboprophylaxis, VTE treatment, and anticoagulation in individuals with MHVs. These findings should be interpreted in light of small sample sizes, wide 95% CIs, and low CoE; and not as evidence of comparable effectiveness or safety.
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Ashraf et al. (2026) conducted a meta-analysis in Pregnancy requiring prevention and treatment of venous thromboembolism or in individuals with mechanical heart valves. Low-molecular-weight heparins (LMWHs) vs. Different dosing regimens was evaluated on Maternal death, thromboembolic complications (TECs), and major bleeding. Pooled event rates for thromboembolic complications and major bleeding overlapped across fixed, weight-based, and anti-Xa-monitored LMWH dosing regimens during pregnancy.
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