title: Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients.
abstract: 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.
authors.affiliation: Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Tschudi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alberio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001772:Blood Cell Count; D001792:Blood Platelets / Q000166:cytology; D003401:Creatine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D051437:Renal Insufficiency / Q000150:complications* / Q000188:drug therapy; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; D003401:Creatine; C083544:lepirudin