Anti-Xa Levels With Venous Thromboembolism Prophylaxis in Critical Care: A Systematic Review and Meta-Analysis.

Abstract

To determine the relationships between subprophylactic anti-Xa levels and low-molecular-weight heparin (LMWH) thromboprophylaxis regimens with venous thromboembolism (VTE) risk, and to identify predictors of subprophylactic anti-Xa levels in critically ill adults. Medline and Embase were searched from inception to May 7, 2025. We included studies enrolling critically ill adults receiving LMWH thromboprophylaxis and assessing the relationship between anti-Xa levels and risk of subprophylactic measurements associated with: 1) standard dosing strategies; 2) VTE risk; or 3) predisposing factors. We extracted or calculated mean, sd, median, interquartile range, mean difference (MD), unadjusted odds ratios (uORs), and adjusted odds ratios (aORs), when available. Risk of bias was evaluated using Cochrane tools. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We included 39 studies (7124 patients). The proportion of patients receiving LMWH prophylaxis achieving target anti-Xa levels was 47% (95% CI, 36-57%). Subprophylactic anti-Xa levels were associated with an increased risk of VTE (uOR, 2.87; 95% CI, 1.42-5.81; low certainty). Variables with a moderate certainty association with subprophylactic anti-Xa levels include male sex (aOR, 2.65; 95% CI, 1.07-6.56), increased weight (MD, 4.90 kg higher weight compared with those with target levels; 95% CI, 2.78-7.02), and elevated body mass index (MD, 1.36 per kg/m2 higher compared with those with target levels; 95% CI, 0.64-2.09). Less than half of critically ill patients achieved their prophylactic anti-Xa targets despite LMWH thromboprophylaxis. Subprophylactic anti-Xa levels may be associated with an increased risk of VTE. Male sex, increased weight, and elevated body mass index have a moderate certainty association with developing subprophylactic anti-Xa levels. This study highlights the clinical importance of anti-Xa level monitoring in critically ill adults and the need for a future randomized controlled trial to further evaluate this topic.