BACKGROUND:Nafamostat mesilate (FUT-175) is a synthetic serine protease inhibitor that inactivates coagulation, fibrinolysis, and platelet aggregation. Nafamostat mesilate may suppress the blood-foreign surface reaction similar to biocompatible materials by blocking factor XIIa. METHODS: We performed an in vitro study of cardiopulmonary bypass (CPB) with fresh human blood among the following three groups: standard CPB sets (C), biocompatible CPB sets (B), and standard CPB sets with FUT-175 (10 mg/L) (F). A clinical study using these same CPB groups also was performed in 45 patients undergoing aortocoronary bypass operations (15 patients each). We injected FUT-175 at 40 mg/h during CPB. RESULTS: In the in vitro study, both groups B and F showed significantly lower levels of coagulation factors, thrombin-antithrombin III complex, fibrinopeptide A, beta-thromboglobulin, complement C3a, granulocyte elastase, and free hemoglobin than group C at the conclusion of the study. Thrombin-antithrombin III complex and free hemoglobin in group F also were lower than in group B. The platelet count remained at a higher level in group F than in the other groups. Separation of bradykinin was suppressed most significantly in group F. In the clinical study, group F also showed significantly lower levels of alpha 2-plasmin inhibitor plasmin complex and C3a than both groups C and B. There were minimal levels of free hemoglobin in group F. CONCLUSIONS:Nafamostat mesilate may contribute major beneficial effects toward conservation of blood during CPB and prevention of coagulopathy after CPB.
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BACKGROUND:Nafamostat mesilate (FUT-175) is a synthetic serine protease inhibitor that inactivates coagulation, fibrinolysis, and platelet aggregation. Nafamostat mesilate may suppress the blood-foreign surface reaction similar to biocompatible materials by blocking factor XIIa. METHODS: We performed an in vitro study of cardiopulmonary bypass (CPB) with fresh human blood among the following three groups: standard CPB sets (C), biocompatible CPB sets (B), and standard CPB sets with FUT-175 (10 mg/L) (F). A clinical study using these same CPB groups also was performed in 45 patients undergoing aortocoronary bypass operations (15 patients each). We injected FUT-175 at 40 mg/h during CPB. RESULTS: In the in vitro study, both groups B and F showed significantly lower levels of coagulation factors, thrombin-antithrombin III complex, fibrinopeptide A, beta-thromboglobulin, complement C3a, granulocyte elastase, and free hemoglobin than group C at the conclusion of the study. Thrombin-antithrombin III complex and free hemoglobin in group F also were lower than in group B. The platelet count remained at a higher level in group F than in the other groups. Separation of bradykinin was suppressed most significantly in group F. In the clinical study, group F also showed significantly lower levels of alpha 2-plasmin inhibitor plasmin complex and C3a than both groups C and B. There were minimal levels of free hemoglobin in group F. CONCLUSIONS:Nafamostat mesilate may contribute major beneficial effects toward conservation of blood during CPB and prevention of coagulopathy after CPB.