Application of a new anticoagulant (nafamostat mesilate) to control hemorrhagic complications during extracorporeal membrane oxygenation—A preliminary report

Abstract

Bleeding related to systemic heparinization has been considered one of the major complications associated with extracorporeal membrane oxygenation (ECMO). Development of the heparin-bonded system will be essential in reducing hemorrhagic complications, but has not yet been clinically proven. The authors chose an alternative approach of making a difference in the activated clotting time (ACT) values between the patient and the ECMO circuit, and decreased only the patient's ACT value, while keeping the value of the ECMO circuit at an ideal level. For this purpose, we have used a very short-life anticoagulant, Nafamostat Mesilate (FUT), while decreasing the dose of heparin. FUT is a synthetic protease inhibitor that has been found to inhibit various kinds of enzyme activities for coagulation. Twelve newborns who had some hemorrhagic complications at various sites before or during ECMO, were selected to receive FUT. The heparin dose was decreased after FUT administration into the drainage route. FUT and heparin doses were regulated to maintain the ACT value at the reinfusion route at 190 to 220 seconds. ACT values at the drainage and the reinfusion routes were simultaneously measured. The average time on FUT was 100.3 ± 86.3 (SD) hours. The average dose of FUT was 0.48 ± 0.22 mg/kg/h, and that of heparin was 21.0 ± 7.5 U/kg/h. The average ACT value at the reinfusion route was 205.7 ± 14.0 seconds compared with that at the drainage route of 178.5 ± 11.8. The difference was statistically significant (P < .001). The average difference in ACT values between both routes was 27.1 ± 7.9 seconds. The bleeding was well controlled by FUT administration in 8 of 12 cases. This report may represent the first clinical use of FUT in neonatal ECMO, and serve as a preliminary study.