Nafamostat mesilate reduces blood-foreign surface reactions similar to biocompatible materials.
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.
Usui
A
A
Division of Cardiac Surgery, Owari Prefectural Hospital, Aichi, Japan.
Hiroura
M
M
Kawamura
M
M
Hibi
M
M
Yoshida
K
K
Murakami
F
F
Tomita
Y
Y
Ooshima
H
H
Murase
M
M
D001550:Benzamidines; D001672:Biocompatible Materials / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000295:instrumentation*; D001026:Coronary Artery Bypass; D004353:Drug Evaluation, Preclinical; D005260:Female; D005549:Foreign-Body Reaction / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D001550:Benzamidines; D001672:Biocompatible Materials; D001779:Blood Coagulation Factors; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D001920:Bradykinin; C032855:nafamostat