R-hirudin as anticoagulant in regular hemodialysis therapy: Finding of therapeutic r-hirudin blood plasma concentrations and respective dosages

Recently heparin-induced thrombocytopenia type II has been diagnosed more f requently and does not exclude hemodialysis patients, Up to now, recombinan t hirudin is the only available anticoagulant showing no immunologic cross reactions with heparin. However, the use of r-hirudin in hemodialysis patie nts with different degrees of residual renal functions is impossible using standard dosages because elimination of r-hirudin varies depending on the d egree of residual renal function. Therefore the first study was carried out using consecutive r-hirudin anticoagulated hemodialyses to determine the a ppropriate dose of r-hirudin. Ten hemodialysis patients with creatinine cle arance values ranging between 0 and 13 ml/min/1.73m(2) were anticoagulated with r-hirudin. An initial bolus of 0.1 mg/kg bwt before the first hemodial ysis, resulted in an average r-hirudin blood concentration of 305 ng/mL at the end of treatment. The dose for each of the following four hemodialyses was adjusted individually to reach the minimum therapeutic r-hirudin blood concentration. At the end of these treatments the mean blood r-hirudin conc entration was 422 ng/mL, The necessary mean doses ranged between 0.008 and 0.125 mg/kg bwt correlating to the creatinine clearance values of the patie nts. All hemodialyses of the study were effective and safe. Bleeding times determined during r-hirudin anticoagulation were significantly lower than c ontrol values measured ? days after a heparin administration, The study pro ved that r-hirudin may he an efficient and safe heparin alternative as a he modialysis anticoagulant when the individual's residual renal function is n oted for dosage and dose adjustment and is controlled by drug monitoring us ing the ecarin clotting time.