Based on the assumption that middle molecules that induce hepatic coma occur in the plasma of patients with fulminant hepatic failure (FHF), the authors have developed a hemodiafiltration (HDF) method using a large-pore poly(methylmethacrylate) (PMMA) membrane that allows proteins to pass through. PMMA HDF resulted in complete recovery of deep coma and long-term survival in a patient with severe FHF. Although a large-scale controlled trial is needed, PMMA HDF is believed to be promising as a future artificial liver support.
Nafamostat mesilate (FUT-175) is a strong protease inhibitor and is used as an anticoagulant in extracorporeal circulation. In the present study, we administered FUT and dipyridamole as anticoagulants during donor plasmapheresis, and the additional effect of dipyridamole was examined. In dogs weighing about 15 Kg, donor plasmapheresis was performed using a cellulose triacetate membrane plasmaseparator (PEX-15, Nipro), and 300 ml of filtrated plasma was obtained within 30 minutes. These dogs were divided into two groups, 50 mg/h of FUT alone was infused (group A, n = 10), and the same dose of FUT and 25 mg/h of dipyridamole were infused (group B, n = 5) during plasmapheresis. Changes of the coagulation system, blood cell counts and complement system were investigated. In clinical cases, an artificial liver support therapy using FUT as an anticoagulant was performed on 8 patients with acute liver failure, and blood compatibility was examined. In dogs, RBC counts and hematocrits were almost stable, but WBC counts were decreased to about 70% of the previous value. Platelets counts were about 60% and 80% of the previous value, in group A and group B, respectively, at the end of the plasmapheresis (P less than 0.01). Clotting factor VII was diminished to about 20% and 35% of the previous value in group A and B, respectively. In clinical cases, all patients received the plasma exchange combined with hemodialysis using FUT as an anticoagulant, and no distinct side effect was observed during plasma exchange.
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