Dose–Response Analysis of Nafamostat Mesylate in Pediatric Critical Care: Implications for Anticoagulation Monitoring During Continuous Venovenous Hemodiafiltration

Nafamostat mesylate (NM) is increasingly used as an alternative anticoagulant during continuous venovenous hemodiafiltration (CVVHDF) in pediatric intensive care, especially when unfractionated heparin or regional citrate is contraindicated. However, evidence regarding optimal monitoring of its anticoagulant effects remains limited. This study aimed to investigate the association between NM infusion rate and coagulation parameters—specifically activated clotting time (ACT) and activated partial thromboplastin time (aPTT)—in critically ill pediatric patients receiving CVVHDF, and to examine how hepatic function and transfusion status may influence this relationship. In this retrospective study of 99 patients, we analyzed 340 matched data pairs of NM infusion orders and coagulation test results. Linear mixed-effects models revealed a significant positive correlation between NM infusion rate and aPTT (β = 8.54, P  < 0.001), while no significant association was found with ACT. Subgroup analyses stratified by liver function and transfusion status consistently supported the association between NM and aPTT. Non-linear regression further suggested a dose–response pattern for aPTT, but not for ACT. These findings indicate that aPTT may be a more sensitive and reliable parameter than ACT for monitoring NM’s anticoagulant effects in pediatric CVVHDF. The results challenge current ACT-based monitoring practices and highlight the need for prospective validation to refine anticoagulation strategies using NM in critically ill children.