Anticoagulation with Nafamostat Mesilate, a Synthetic Protease Inhibitor, in Hemodialysis Patients with a Bleeding Risk

Nafamostat mesilate (FUT) is a synthetic serine protease inhibitor with a short half-life that is used during hemodialysis (HD) in patients with a high risk of bleeding because it does not prolong the systemic coagulation time. To evaluate whether or not FUT is able to effectively prevent clot formation in the extra-corporeal circuit without increasing systemic bleeding, HD using FUT was carried out for 33 sessions in 12 patients with a high risk of bleeding. FUT was continuously infused during HD at 20-40 mg/h to maintain a 2-fold prolongation of activated partial thromboplastin time (APTT) at the dialyzer outlet on the venous side of the circuit. No APTT prolongation was observed on the arterial side of the circuit before FUT infusion, and none of the patients showed increased bleeding during or after HD. However, clots formed in the arterial chamber (30.3%), the dialyzer (36.6%), and the venous chamber (15.1 %). In 2 of the 12 patients, HD was discontinued due to clot formation despite sufficient prolongation of APTT. The mean levels of the thrombin-antithrombin III complex and prothrombin activation fragment 1+2 in the circuit gradually increased on both the arterial and venous sides during HD using FUT, and protein C activity decreased. No significant changes in these parameters occurred during heparin HD in the same patients after the bleeding episode had resolved. Despite sufficient prolongation of APTT in the circuit, FUT was less effective in suppressing thrombin generation when compared to heparin. Therefore, FUT cannot be recommended as an alternative drug to heparin for hemodialysis patients with a bleeding risk.