low-molecular-weight heparin + nafamostat mesilate

This is a combination therapy consisting of low-molecular-weight heparin (LMWH) and nafamostat mesilate. LMWH is an anticoagulant that acts by inhibiting factor Xa and, to a lesser extent, thrombin, thereby preventing the formation of blood clots. Nafamostat mesilate is a synthetic serine protease inhibitor with anticoagulant, antifibrinolytic, anti-inflammatory, and antiviral properties. It inhibits multiple enzymes in the coagulation cascade (including thrombin, factor Xa, and XIIa), as well as components of the fibrinolytic system and complement system. Nafamostat also blocks viral entry by inhibiting TMPRSS2-mediated membrane fusion—a mechanism relevant for SARS-CoV-2 infection[1][3][6]. The combination has been explored primarily in Japan for conditions such as disseminated intravascular coagulation (DIC), especially DIC with enhanced fibrinolysis or high bleeding risk scenarios like COVID-19-associated coagulopathy[1][7]. The rationale for combining these agents is to leverage LMWH’s strong anticoagulation effect with nafamostat’s potent antifibrinolytic action while minimizing bleeding risk[1].