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 frequently and does not exclude hemodialysis patients. Up to now, recombinant hirudin is the only available anticoagulant showing no immunologic cross reactions with heparin. However, the use of r-hirudin in hemodialysis patients with different degrees of residual renal functions is impossible using standard dosages because elimination of r-hirudin varies depending on the degree of residual renal function. Therefore the first study was carried out using consecutive r-hirudin anticoagulated hemodialyses to determine the appropriate dose of r-hirudin. Ten hemodialysis patients with creatinine clearance values ranging between 0 and 13 mL/min/1.73m2 were anticoagulated with r-hirudin. An initial bolus of 0.1 mg/kg bwt before the first hemodialysis, 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 concentration 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 patients. All hemodialyses of the study were effective and safe. Bleeding times determined during r-hirudin anticoagulation were significantly lower than control values measured 2 days after a heparin administration. The study proved that r-hirudin may be an efficient and safe heparin alternative as a hemodialysis anticoagulant when the individual's residual renal function is noted for dosage and dose adjustment and is controlled by drug monitoring using the ecarin clotting time.
Bucha
E
E
Max-Planck-Gesellschaft eV, Research Unit Pharmacological Haemostaseology at the Friedrich Schiller University, Jena, Federal Republic of Germany.
Nowak
G
G
Czerwinski
R
R
Thieler
H
H
D000328:Adult; D001760:Bleeding Time; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D006435:Renal Dialysis / Q000379:methods; D051437:Renal Insufficiency / Q000628:therapy
D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins