1.
Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass
Kaminishi Y, Hiramatsu Y, Watanabe Y, Yoshimura Y, Sakakibara Y
The Annals of Thoracic Surgery. 2004;77((2):):644-50.
Abstract
BACKGROUND The pharmacological inhibition of blood-foreign surface interactions is an attractive strategy for reducing the morbidity associated with cardiopulmonary bypass. We compared the inhibitory effects of nafamostat mesilate (a broad-spectrum synthetic protease inhibitor) and minimal-dose aprotinin on blood-surface interactions in clinical cardiopulmonary bypass. METHODS Eighteen patients undergoing coronary surgery were divided into three groups: (1) the control group (heparin, 4 mg/kg; n = 6), (2) the nafamostat mesilate group (heparin plus nafamostat, 0. 2 mg/kg bolus followed by 2. 0 mg/kg/h during cardiopulmonary bypass; n = 6), and (3) the aprotinin group (heparin plus aprotinin, 2. 0 x 10(4) KIU/kg; n = 6). Platelet count, platelet aggregation, beta-thromboglobulin, prothrombin fragment F1. 2, thrombin-antithrombin complex, plasminogen activator inhibitor-1, alpha2-plasmin inhibitor-plasmin complex, D-dimer, neutrophil elastase, and interleukin-6 were measured before, during, and after bypass. Bleeding times and blood loss were recorded. RESULTS There were no significant differences between groups in platelet count, beta-thromboglobulin, plasminogen activator inhibitor-1, interleukin-6, bleeding times, or blood loss. Platelet aggregation was better preserved at 12 hours after surgery in the nafamostat and aprotinin groups than in the control group. Prothrombin fragment F1. 2, thrombin-antithrombin complex and neutrophil elastase levels were significantly reduced by aprotinin, but not by nafamostat as compared with the control group. The alpha2-plasmin inhibitor-plasmin complex and D-dimer were significantly lower with either of the drugs. Aprotinin showed better control of D-dimer than did nafamostat. CONCLUSIONS Nafamostat mesilate fails to reduce thrombin formation and neutrophil elastase release, whereas minimal-dose aprotinin inhibits both. Neither nafamostat nor aprotinin inhibits platelet activation. Nafamostat reduces fibrinolysis during cardiopulmonary bypass, although its effect is not as potent as aprotinin.
2.
Effect of low-dose aprotinin on coagulation and fibrinolysis in cardiopulmonary bypass
Kawasuji M, Ueyama K, Sakakibara N, Tedoriya T, Matsunaga Y, Misaki T, Watanabe Y
Annals of Thoracic Surgery. 1993;55((5):):1205-9.
Abstract
To study the effect of low-dose aprotinin on hemostasis in patients undergoing cardiopulmonary bypass (CPB) for coronary artery bypass operations and to elucidate the mechanism of aprotinin action, we randomized 14 of 27 patients to receive 30,000 KIU/kg aprotinin in the CPB priming volume and 7,500 KIU/kg aprotinin intravenously each hour during CPB (1 patient was excluded from the aprotinin group because of protamine shock). Intraoperative and postoperative blood loss was significantly reduced in the aprotinin group. Antithrombin III level was significantly decreased, and the levels of thrombin-antithrombin III complexes were significantly increased during CPB in both groups, indicating activation of the clotting system. The marked increase in fibrin(ogen) degradation products during CPB in the control group, indicating enhanced fibrinolytic activity, was significantly reduced in the aprotinin group. alpha 2-Plasmin inhibitor was significantly reduced during CPB in the control group. The marked increase in alpha 2-plasmin inhibitor-plasmin complexes in the control group, indicating plasmin activity, was significantly reduced in the aprotinin group. A marked decrease in the platelet count was observed during CPB similarly in both groups. These findings demonstrated that low-dose aprotinin administration was effective in reducing intraoperative and postoperative blood loss and that activation of the clotting system during CPB was not followed by hyperfibrinolysis in aprotinin-treated patients. The improved hemostasis is mainly attributable to the prevention of hyperfibrinolysis during CPB.