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

Abstract

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.

Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

“…The primary elimination route of lepirudin is renal, accounting for approximately 90% of its systemic clearance [5]. The systemic clearance of lepirudin is proportional to the glomerular filtration rate and there is a relevant cumulation of this drug in patients with renal impairment [6]. Furthermore bleeding is the most important and clinically relevant complication of treatment with lepirudin when compared to oral or parenteral Xa inhibitors, with an incidence rate of 4%–19% [7].…”

Lepirudin in the management of patients with heparin-induced thrombocytopenia

“…About 35% of lepirudin is excreted in the urine unchanged (Meyer et al 1990; Nowak et al 1992). The systemic clearance of lepirudin is proportional to the glomerular filtration rate (Bucha et al 1999b). Therefore, the half-life of the drug increases with deterioration of renal function (Nowak et al 1992, 1997; Vanholder et al 1997).…”

“…However, case reports and observational studies have shown that the drug can be safely used in this patient group (Nowak et al 1997; Bucha et al 1999b; Fischer et al 1999; Saner et al 2001; Gajra et al 2007). …”

Hirudin In Renal Insufficiency

“…3,4 Renal r-hirudin clearance is proportional to creatinine clearance. 10,11 However, it should subjects with moderate renal insufficiency (Cl Cr 36 to 59 mL/min) both total and renal r-hirudin clearance were already reduced to less than one third. In participants with severe renal insufficiency (Cl Cr 12 to 27 mL/ min), total and renal r-hirudin clearance were decreased by a factor 8 and a factor 10, respectively, compared with healthy controls.…”