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effect of nafamostat on the coagulation pathway is weak compared with that on the fibrinolytic pathway. Therefore, Yamada et al. recommended combination therapy with nafamostat and heparin, because the latter inhibits the coagulation pathway. Recently, Yamamoto et al. reported that nafamostat has a direct viral effect against SARS-CoV-2, mediated by the inhibition of viral entry into host cells. Nafamostat might be effective against COVID-19 owing to both its antiviral and anti-DIC activity. However, the dose of nafamostat in DIC treatment is 10 times higher than that in pancreatitis treatment. The optimal dose of nafamostat for treating COVID-19 in combination with heparin remains unclear. Although nafamostat does not exhibit severe hemorrhagic side effects, its optimal dosage and the screening method for its efficacy should be established for clinical use. Further analysis is required to confirm the efficacy and safety of combination therapy with heparin and nafamostat in patients with COVID-19 who are undergoing ECMO. Bleeding has often been observed in COVID-19 patients during ECMO. Management of these patients with treatments such as cryoprecipitate and the combination of nafamostat and heparin should be analyzed in large-scale studies.

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