Article: article from journal or magazin.
Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients.
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
The recommended dose (bolus 0.4 mg/kg followed by 0.15 mg/kg per hour) of lepirudin, a direct thrombin inhibitor licensed for treatment of heparin-induced thrombocytopenia (HIT), is too high. Starting in 2001, we omitted the bolus and reduced maintenance dose by at least one-third. Analyzing 53 HIT patients treated between January 2001 and February 2007, we observed that therapeutic anticoagulation intensity already 4 hours after lepirudin start had been reached with the following initial lepirudin doses (median): 0.078 mg/kg per hour [creatinine clearance (CrCl) more than 60 mL/min], 0.040 mg/kg per hour (CrCl 30-60 mL/min), and 0.013 mg/kg per hour (CrCl < 30 mL/min). The efficacy of this treatment was documented by increasing platelets and decreasing D-dimers. Based on this experience, we derived a lepirudin dosing regimen, which was prospectively evaluated treating 15 HIT patients between March 2007 and February 2008. We show that omitting the initial lepirudin bolus and administering 0.08 mg/kg per hour in patients with CrCl more than 60 mL/min, 0.04 mg/kg per hour in patients with CrCl 30-60 mL/min, and 0.01 to 0.02 mg/kg per hour in those with CrCl less than 30 mL/min is efficacious and safe, as documented by increasing platelet counts, decreasing D-dimer levels, and rare thrombotic (1 of 46) and major bleeding (4 of 46) complications.
Adult, Aged, Aged, 80 and over, Anticoagulants/administration & dosage, Anticoagulants/adverse effects, Blood Cell Count, Blood Platelets/cytology, Creatine/metabolism, Dose-Response Relationship, Drug, Female, Heparin/adverse effects, Hirudins/administration & dosage, Hirudins/adverse effects, Humans, Kidney/physiopathology, Male, Metabolic Clearance Rate, Middle Aged, Recombinant Proteins/administration & dosage, Recombinant Proteins/adverse effects, Renal Insufficiency/complications, Renal Insufficiency/drug therapy, Retrospective Studies, Thrombocytopenia/chemically induced, Thrombocytopenia/complications, Treatment Outcome
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