Lepirudin dosing in dialysis-dependent renal failure

Lepirudin is a direct thrombin inhibitor indicated for parenteral anticoagu lation in patients with heparin-induced thrombocytopenia. In patients with normal renal function, a bolus dose of 0.4 mg/kg is injected over 15-20 sec onds, followed by a continuous infusion of 0.15 mg/kg/hour adjusted to prol ong the activated partial thromboplastin time (aPTT) to 1.5-2.5 times the p atient's baseline. Because renal function directly influences lepirudin eli mination, patients with renal impairment require significant adjustments in the initial infusion rate. Current recommendations suggest that patients w ith dialysis-dependent renal failure should receive an initial bolus of 0.2 mg/kg, followed by 0.1 mg/kg every other day if the aPTT falls below the l ower limit of the therapeutic range; however, this dosing may result in sig nificant and prolonged overanticoagulation. A review of available literatur e regarding pharmacokinetics of lepirudin in renal failure suggests conside rable variability in patient response over a narrow creatinine clearance ra nge. Because there is no antidote for lepirudin if significant bleeding occ urs, lower and less frequent dosing, guided by aPTT results, is recommended .