Ability of Nafamostat Mesilate to Prolong Filter Patency during Continuous Renal Replacement Therapy in Patients at High Risk of Bleeding: A Randomized Controlled Study

Abstract

Continuous renal replacement therapy (CRRT) is considered as an effective modality for renal replacement therapy in hemodynamically unstable patients within intensive care units (ICUs). However, the role of heparin anticoagulation, which is used to maintain circuit patency, is equivocal due to the risk of bleeding and morbidity. Among various alternative anticoagulants, nafamostat mesilate has been shown to be an effective anticoagulant in patients prone to bleeding. Hence, we conducted a prospective, randomized controlled study investigating the effect of nafamostat mesilate on mortality, CRRT filter life span and adverse events in patients with bleeding tendency. Seventy-three Patients were randomized into either the futhan or no-anticoagulation group. Thirty-six subjects in the futhan group received nafamostat mesilate, while thirty seven subjects in the no-anticoagulation group received no anticoagulants. Baseline characteristics and appropriate laboratory tests were taken from each group. The mortality between the two groups was not significantly different. Nevertheless, between the futhan group and the no-anticoagulation group, the overall number of filters used during CRRT (2.71±2.12 vs. 4.50±3.25; p = 0.042) and the number of filters changed due to clots per 24 hours (1.15±0.81 vs. 1.74±1.62; p = 0.040) were significantly different. When filter life span was subdivided into below and over 12 hours, the number of filters functioning over 12 hours was significantly higher in the futhan group than in the no-anticoagulation group (p = 0.037, odds ratio 1.84). There were no significant differences in transfusion, mortality, or survival between the two groups, and no adverse events related to nafamostat mesilate were noted. Hence, nafamostat mesilate may be used as an effective and safe anticoagulant, without increasing the risk of major bleeding complications, in patients prone to bleeding.Trial RegistrationClinicaltrials.gov NCT01761994

Continuous Renal Replacement Therapy and Anticoagulation:

“…47 Use of nafamostat can improve circuit life in some patients. [47][48][49] The inhibitor has not been approved for use in the United States for CRRT anticoagulation; it is predominantly used in Japan.…”

“…3,47,48,50 Platelet-Inhibiting Agents Prostacyclin (prostaglandin I 2 ) is a paracrine hormone of the prostaglandin family. It is secreted by the vascular tissue and has various effects related to the suffi ciency of blood fl ow.…”

Paroxysmal Nocturnal Hemoglobinuria: From Bench to Bed

“…-Nafamostat is a synthetic serine protease inhibitor of C1s and other proteases currently is only approved in a limited market (Japan and Korea).Other small molecule inhibitors of C1s have also been characterized; however, to our knowledge, the role of these inhibitors in transfusion-related indications has not been reported [27]. -C1 esterase inhibitor-C1 esterase inhibitor (C1INH) is a concentrate derived from human plasma that is used to treat C1 esterase deficiency, responsible for hereditary or acquired angioedema.…”

Application of Continuous Renal Replacement Therapy: What Should We Consider Based on Existing Evidence?

“…Therefore, this anticoagulant is not expected to exacerbate bleeding. Evidence from both observational [58] and interventional [59,60] studies have demonstrated its utility in CRRT.…”