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Anti-Xa Levels With Venous Thromboembolism Prophylaxis in Critical Care: A Systematic Review and Meta-Analysis
Kevin M Durr1,2, Alexa Ehlebracht3, Bram Rochwerg4,5,6
1Department of Critical Care, University of Ottawa, The Ottawa Hospital, Ottawa, ON, Canada.
Critical Care Medicine
|March 11, 2026
Summary
Less than half of critically ill patients achieve therapeutic anti-factor Xa levels with low-molecular-weight heparin prophylaxis, increasing venous thromboembolism risk. Male sex, higher weight, and BMI predict subprophylactic levels.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Thrombosis Research
Background:
- Low-molecular-weight heparin (LMWH) is standard for venous thromboembolism (VTE) prophylaxis in critically ill adults.
- Therapeutic anti-factor Xa (anti-Xa) levels are crucial for effective LMWH prophylaxis.
- Subprophylactic anti-Xa levels may compromise VTE prevention in this vulnerable population.
Purpose of the Study:
- To investigate the association between subprophylactic anti-Xa levels and VTE risk in critically ill patients receiving LMWH.
- To identify predictors of subprophylactic anti-Xa levels in this patient group.
Main Methods:
- Systematic review and meta-analysis of Medline and Embase databases.
- Inclusion of 39 studies with 7124 critically ill adults receiving LMWH.
- Extraction of data on anti-Xa levels, VTE events, and patient characteristics; assessment of evidence certainty using GRADE.
Main Results:
- Only 47% of patients achieved target anti-Xa levels.
- Subprophylactic anti-Xa levels were linked to a 2.87-fold increased VTE risk (low certainty).
- Male sex, increased weight, and elevated BMI were associated with subprophylactic anti-Xa levels (moderate certainty).
Conclusions:
- Suboptimal anti-Xa levels are common in critically ill patients on LMWH, potentially increasing VTE risk.
- Monitoring anti-Xa levels and considering patient factors like sex, weight, and BMI is clinically important.
- Further randomized controlled trials are needed to optimize LMWH dosing and monitoring strategies.
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