Validation of Nafamostat Mesilate as an Anticoagulant in Extracorporeal Membrane Oxygenation: A Large-Animal Experiment

Abstract

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxy-genation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical out-comes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thrombo-plastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin (IL)-1β levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anti-coagulation in ECMO.

Keywords

• Extracorporeal membrane oxygenation
• Anticoagulants
• Nafamostat mesilate