The role of anti-Factor-Xa monitoring in the dosing and administration of low molecular weight heparins in pregnancy: a systematic review and meta-analysis.

Background

Our aim was to determine the risk of thromboembolic complications (TECs) and major bleeding with weight-based, fixed- and anti-Xa-monitored dosing of low molecular weight heparins (LMWH) during pregnancy.

Methods

We conducted a systematic review wherein we searched seven databases for articles published before August 2024 that reported on dosing and monitoring of LMWH during pregnancy. We calculated event rates and 95% confidence intervals (95%CI) for maternal death, TECs and major bleeding using random effects meta-analysis. We assessed Risk-of-bias using Quality In Prognosis Studies tool and certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Findings

We identified 5007 studies, of which 94 studies (53 case series, 30 cohort and 11 randomized trials) were eligible. For thromboprophylaxis and treatment of venous thromboembolism (VTE), fixed-, weight-based, and anti-Xa-guided LMWH doses had broadly overlapping pooled event rates for TECs and major bleeding. For mechanical heart valves (MHVs), the risk of death, TECs and major bleeding was 2.7% (95%CI 0.3-6.5%), 7.9% (2.8- 14.6%) and 8.4% (2.0 -17.2%) respectively. The CoE for all estimates were low-to-very-low, mainly due to imprecision, risk-of-bias and publication bias.

Interpretation

The pooled single-arm event rates and confidence limits appeared broadly overlapping for the main outcomes across various LMWH dosing regimens currently used in pregnancy for thromboprophylaxis, treatment of VTE and anticoagulation in individuals with MHVs. These findings should be interpreted in the light of small sample sizes, wide 95%CIs and low CoE and not as evidence of comparable effectiveness or safety.