Anticoagulation with nafamostat mesilate during extracorporeal life support

Nafamostat mesylate (NM) affects coagulation and fibrinolysis and impedes obesity-associated protein demethylase activity, which regulates Na⁺/K⁺ transport properties and the NF-κB signaling pathway. NM significantly decreases macrophage, neutrophil, and T lymphocyte infiltration, thereby reducing inflammation and apoptosis after reperfusion and promoting recovery in patients with severe conditions such as near-fatal asthma and cardiac arrest. Extracorporeal life support (ECLS) devices are used for cardiac and/or pulmonary support as a bridge to recovery, decision, surgery, or transplant in patients with refractory cardio-circulatory or respiratory diseases and provide essential opportunities for organ support and patient survival. However, they can lead to some potential adverse events such as hemorrhage and thrombosis. NM provides a sustained innate immune response of coagulation and anti-inflammation in extracorporeal circuits, principally due to its activation of the contact and complement systems. Heparin is the main anticoagulant used in extracorporeal circuits; however, it may cause massive bleeding and heparin-induced thrombocytopenia. Although no antidote is available, NM has a very short half-life of approximately 8-10 min and might have positive effects on patients who require coagulation and anti-inflammation. NM has been used for anticoagulation in continuous renal replacement therapy, extracorporeal membrane oxygenation, hemodialysis, and left ventricular assist devices. In this review, we focused on the pharmacology, monitoring parameters, and considerations for the special use of NM in patients receiving ECLS. Our findings suggest that systemic anticoagulation with NM during ECLS might be a feasible and safe alternative with several advantages for critically ill patients with high-risk bleeding and might improve their prognosis.