Effects of Nafamostat Mesilate on ADP-Induced Platelet Aggregation and Disaggregation in Hemodialysis Patients

Abstract

Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECC) in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 microM ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) microg/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 microg/mln or higher. Moreover, NM almost completely disaggregated at 100 microg/ml. This NM concentration of 1.0 microg/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10 M(-5)). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.

Hemodialysis effect on platelet count and function and hemodialysis-associated thrombocytopenia

“…Similarly, nafamostat mesilate, a protease inhibitor that can be used as an alternative anticoagulant for dialysis, has been shown to markedly attenuate the platelet aggregation normally seen during dialysis. 65 The effects of other alternative anticoagulants and of various anti-platelet drugs on dialysis-associated platelet activation is a topic that has not been well studied and merits further investigation.…”

Acute non‐heparin‐induced thrombocytopenia during hemodiafiltration in a patient with multiple myeloma

“…21 Furthermore, NM inhibits platelet aggregation and disaggregates already aggregated platelets. 21 Fuse et al 22 have suggested that NM suppresses activated glycoprotein IIb-IIIa expression. The reason that platelet reduction was not observed during NM use may be attributed to its potent inhibitory effect on coagulation and platelet aggregation.…”

“…Nafamostat mesilate, a serine protease inhibitor, has potent inhibitory effects on thrombin, coagulation factor XIIa, factor Xa, factor VIIa, kallikrein, plasmin, compliment factors, and trypsin . Furthermore, NM inhibits platelet aggregation and disaggregates already aggregated platelets . Fuse et al have suggested that NM suppresses activated glycoprotein IIb‐IIIa expression.…”

Nafamostat prevents hypothermia and improves survival time after administration of lipopolysaccharide in a mouse surgical model

“…Nafamostat is a trypsin-like serine protease inhibitor, which has an anticoagulant effect [13]. In Japan, nafamostat is used as an alternative to heparin as an anticoagulant during continuous hemodialysis and fi ltration [14]. It is possible that nafamostat, like heparin, may have a protective effect against LPS-induced DIC and subsequent septic shock.…”

“…It is widely used during continuous hemodialysis and fi ltration [14], and may show effects against sepsis similar to those shown by other anticoagulants [10]. In murine models, low-molecular-weight heparin attenuates multiple organ failure following LPS-induced DIC and septic shock [10].…”