Nafamostat Mesilate Reduces Blood Loss During Open Heart Surgery

BackgroundNafamostat mesilate (FUT-175) is a protease inhibitor inactivating coagulation, fibrinolysis, and platelet aggregation. A prospective, randomized trial was performed to assess the efficacy of FUT-175 in the reduction of postoperative bleeding tendency. Methods and ResultsFUT-175 was infused at a rate of 40 mg/h during cardiopulmonary bypass (CPB) along with 300 IU/kg of heparin in 20 patients undergoing aortocoronary bypass surgery (FUT group). This group was compared with another group of 20 patients undergoing aortocoronary bypass surgery, who were given only heparin (control group). Blood concentrations of FUT-175 and activated clotting time increased after cooling, peaking at 2050±1190 ng/mL and 2136±983 seconds at the lowest temperature and recovered after rewarming to values of 166± 118 ng/mL and 510± 148 seconds, respectively, at the end of CPB. In the FUT group, platelet counts were significantly higher at the end of CPB than those in the control group (168±10 versus 136+9x103/mm3, P<.05). In the FUT group, serum concentrations of, 8-thromboglobulin (307±102 versus 537±391 ng/mL, P<.05), PIC (3.6±1.7 versus 5.8±3.8μg/mL, P<.05) and FDP (20.2±7.0 versus 41.4±11.9 ng/mL, P<.01) were significantly lower than those in the control group at the end of CPB. However, serum concentrations of TAT, FPA, and FPB, B 15–42 showed no significant differences between groups. FUT-175 significantly reduced heparin dosage and 24-hour postoperative blood loss (19 200±3200 versus 29 100±7700 IU, P<.01, and 382±129 versus 576±375 mL, P<.05). ConclusionsFUT-175 inhibits fibrinolysis and preserves platelet counts and function during CPB and reduces blood loss during open heart surgery.

[1]  J. Umlas.  Fibrinolysis and Disseminated Intravascular Coagulation in Open Heart Surgery , 2003, Transfusion.

[2]  Y. Fujiyama,et al.  Amidinonaphthol derivatives directly inhibit the ligand binding on platelet glycoprotein IIb–IIIa , 1995 .

[3]  R. Weisel,et al.  Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass. , 1988, The Journal of thoracic and cardiovascular surgery.

[4]  W. van Oeveren,et al.  Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. , 1987, The Annals of thoracic surgery.

[5]  T. Bateman,et al.  Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: reduction in blood product usage with desmopressin. , 1987, Journal of the American College of Cardiology.

[6]  A. Schmaier,et al.  Fibrinogen receptors in platelet adhesion to surfaces of extracorporeal circuit. , 1987, The American journal of physiology.

[7]  R. Weintraub,et al.  Treatment with Desmopressin Acetate to Reduce Blood Loss after Cardiac Surgery , 1986 .

[8]  R. Bick.  Hemostasis Defects Associated with Cardiac Surgery, Prosthetic Devices, and Other Extracorporeal Circuits , 1985, Seminars in thrombosis and hemostasis.

[9]  S. Fujii,et al.  Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system. , 1985, Haemostasis.

[10]  R. Colman,et al.  Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation. , 1985, The Journal of laboratory and clinical medicine.

[11]  T. Sato,et al.  Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments. , 1984, Japanese journal of pharmacology.

[12]  S. Fujii,et al.  Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor. , 1982, International archives of allergy and applied immunology.

[13]  R. Colman,et al.  Platelet function during cardiac operation: comparison of membrane and bubble oxygenators. , 1982, The Journal of thoracic and cardiovascular surgery.

[14]  S. Fujii,et al.  New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. , 1981, Biochimica et biophysica acta.

[15]  E. Hessel,et al.  Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. , 1980, Blood.

[16]  E. Salzman,et al.  Elevated Plasma Fibrinopeptide A ana Thromboxane B2 Levels During Cardiopulmonary Bypass , 1980, Circulation.

[17]  G. Brecher,et al.  INCIDENCE OF BLEEDING IN CARDIAC SURGERY WITH EXTRACORPOREAL CIRCULATION , 1964, Annals of the New York Academy of Sciences.

[18]  R. Colman,et al.  Thromboxane synthesis and platelet secretion during cardiopulmonary bypass with bubble oxygenator. , 1980, The Journal of thoracic and cardiovascular surgery.

[19]  R. Colman,et al.  Effects of prostaglandin E1 on platelet loss during in vivo and in vitro extracorporeal circulation with a bubble oxygenator. , 1979, The Journal of thoracic and cardiovascular surgery.