A retrospective Cohort study on the effect of the LOw-molecular weighT heparin (LMWH) nadroparin dose on anti-XA levels in a mixed medical-surgical ICU population: CLOT-Xa

Purpose: Low-molecular-weight heparins (LMWHs) are widely used for prevention and treatment of venous thromboembolism (VTE) in critically ill patients. The objective of this study was to assess the dose-response relationship between nadroparin dose and anti-Xa activity in ICU patients.

Materials and methods: Critically ill adult patients who were admitted to the ICU, and received at least three subcutaneous injections of nadroparin were included. The dose-effect relationship between nadroparin dose and anti-Xa level was analysed through a mixed-effects logistic regression model.

Results: In total, 327 ICU patients were included. Median anti-Xa levels ranged from <0.1 IU/mL after nadroparin 0-37 IU/kg/day to 0.6 IU/mL after nadroparin >85 IU/kg/day (p < 0.01). Among all 1520 anti-Xa measurements, 859 (57 %) measurements were in the desired anti-Xa range. The best adequacy of anti-Xa levels was observed in nadroparin doses of 38-85 IU/kg (73 %). No differences in the odds of bleeding events or VTE between different anti-Xa levels were found.

Conclusions: We found a clear dose-response relationship between nadroparin dose and anti-Xa levels. Increasing nadroparin doses led to more adequate anti-Xa levels without a change in the occurrence of VTE or major bleeding events, suggesting that LMWH therapy can be successfully and safely personalized using anti-Xa guided dosing.