A comparison between the use of recombinant hirudin and heparin during hemodialysis

Abstract

The purpose of this study was to determine the anticoagulant and antithrombotic potential of hirudin during hemodialysis by comparing the efficacy of dialysis with heparin to that of dialysis with recombinant hirudin (r-hirudin). Eleven patients with chronic renal failure and on maintenance hemodialysis were included in this open cross-over study. Conventional doses of heparin were administered during the first dialysis of the study. Two days later r-hirudin, at a dose of 0.15 mg/kg, was given as a bolus at the start of the second dialysis. The mean decreases in plasma levels of urea, uric acid and creatinine were approximately 50% after dialysis with both anticoagulants. Dialysis was therefore equally effective. However, effective dialysis with r-hirudin was achieved with a shorter activated partial thromboplastin time (APTT; range 65 to 103 seconds) compared to that with heparin (> 120 seconds), thereby decreasing the risk of bleeding. Markedly less 111In-labeled platelets accumulated at the inlet of the artificial kidney when r-hirudin was used, suggesting a smaller loss of hollow fiber volume. The results indicate that hirudin may be a suitable alternative anticoagulant for use during hemodialysis and it thus warrants further investigation.

R-Hirudin as Anticoagulant in Regular Hemodialysis Therapy: Finding of Therapeutic R-Hirudin Blood/Plasma Concentrations and Respective Dosages

“…The first two successive hemodialyses using r-hirudin as an anticoagulant in humans were carried out in 1989 by Thieler et al (12). The results were confirmed by studies of Vanholder et al (13) and van Wyk et al (14) who used r-hirudin only for single hemodialysis sessions.…”

“…Vanholder et al (13) described a dose titration of r-hirudin to the occurence of clotting. With the found effective r-hirudin dose of 0.08 mg/kg bwt, 14 patients with a creatinine clearance <7 mL/min were treated to perform a single hemodialysis. The reached r-hirudin plasma concentrations at the end of this treatment varied between 327 and 1235 ng/mL (mean = 527.7 ng/mL).…”

A Case Series Describing the Use of Argatroban in Patients on Extracorporeal Circulation

“…In the presence of normal kidney function, their half-life is similar to argatroban, although some patients who require ECLS may have renal insufficiency thus extending the half-life. In renal dysfunction, the half-life of lepirudin and bivalirudin may be extended to days, 16 placing patients at risk of coagulopathic complications. 17 Both aPTT and ACT may be used to monitor anticoagulation while on ECLS.…”

Adequate Management of Heparin-Associated Thrombocytopenia

“…The usage of danaparoid is compromised by two disadvantages: (1) there exists a cross-reactivity of the HAT II antibodies towards this agent in approximately 10% of the cases, and (2) its anticoagulative half-life is quite prolonged, especially in end-stage renal disease. As therapeutic alternative recombinant hirudin (lepirudin; HBW 023, Refludan ® ) has proven its clinical usefulness as parenteral safe anticoagulant in different prospective studies [20, 21, 22]. Lepirudin is now approved in the European Community for the treatment of HAT type II.…”