Nafamostat Mesilate Reduces Blood Cell Adhesion to Cardiopulmonary Bypass Circuits: An In-Vitro Study

Abstract

Nafamostat mesilate (FUT-175) is a protease inhibitor, working as an inactivator of coagulation, fibrinolysis and platelet aggregation. Although FUT-175 directly blocks contact factors in coagulation, it also may decrease activation of humoral cascade systems when used in cardiopulmonary bypass circuits. We performed an in vitro study using fresh human blood in the following cardiopulmonary bypass circuits: standard circuit (C), biosurfaced circuit (B) and standard circuit containing FUT-175 (F). Each circuit was primed with 500 ml of electrolyte solution and 500 ml of fresh blood. Cardiopulmonary bypass was performed using a roller pump for four hours in two sets of each circuit configuration. Platelet factors (platelet count and beta-thromboglobulin), coagulation factors (thrombin-antithrombin III complex and fibrinopeptide A), fibrinolysis factors (alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor), complement factors (C3a, C4a), free hemoglobin, and granulocyte elastase were measured at the beginning and end of the study. Hemocytograms were measured concurrently. The FUT-175 group showed significantly lower levels ofthe measured indices than the biosurfaced group in thrombin-antithrombin III complex (7.4±2.1 vs. 54.9±38.1 ng/ml), fibrinopeptide A (7.2±2.0 vs. 20.2±14.6 ng/ml), beta-thromboglobulin ( 1940±250 vs. 2438±314 ng/ml) and free hemoglobin (25.2±14.3 vs. 73.8±18.4 mg/dl). There were no significant differences between Group F and Group B in platelet count, C3a, C4a and granulocyte elastase, although these indices were significantly lower in Groups F and B when compared to Group C. Therefore, FUT-17 5 appears to reduce blood-foreign surface reaction and diminishes cellular adhesion to the inner surface of the cardiopulmonary bypass circuit.