By interfacing a polyacrylonitrile (PAN)-polyethyleneoxide (PEO) membrane with an ionically heparin-bound catheter, tubing, and module header, a totally antithrombogenic continuous ultrafiltration system (ACUS) was developed and its performance, persistent antithrombogenicity, and well-maintained ultrafiltration level were confirmed through animal experiments. Although the amount of heparin released and accumulated in vitro from those heparinized parts was very low and stable (on the order of 1 x 10(-2) U/cm2/min), partial thromboplastin time evaluated in vivo was not elongated during passage through the ACUS. Extracorporeal circulation time with the ACUS in unheparinized dog model was 458 +/- 302 min (n = 24), whereas those of partially modified (antithrombogenic) system did not exceed 100 min. As compared with that in a conventional continuous arteriovenous hemofiltration system, an extracorporeal circulation with the ACUS in an unheparinized dog model revealed significantly less fluctuation of platelet count, and no adherent platelets were observed on the surface of the PAN-PEO membrane. An ACUS consisting of a PAN-PEO membrane and heparinized parts was thus demonstrated to have good platelet compatibility. An ACUS with a surface area of 0.25 m2 was applied to two patients with acute renal failure. Hemofiltration without systemic heparinization lasted for 44 h per hemofilter, and a stable level of ultrafiltration was maintained. This system seems to be applicable for the clinical management of volume overload, especially in patients with bleeding tendencies or postoperative bleeding.
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