Lepirudin dosing in dialysis-dependent renal failure

Lepirudin is a direct thrombin inhibitor indicated for parenteral anticoagulation 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 seconds, followed by a continuous infusion of 0.15 mg/kg/hour adjusted to prolong the activated partial thromboplastin time (aPTT) to 1.5-2.5 times the patient's baseline. Because renal function directly influences lepirudin elimination, patients with renal impairment require significant adjustments in the initial infusion rate. Current recommendations suggest that patients with 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 lower limit of the therapeutic range; however, this dosing may result in significant and prolonged overanticoagulation. A review of available literature regarding pharmacokinetics of lepirudin in renal failure suggests considerable variability in patient response over a narrow creatinine clearance range. Because there is no antidote for lepirudin if significant bleeding occurs, lower and less frequent dosing, guided by aPTT results, is recommended.