title: Argatroban anticoagulation in patients with heparin-induced thrombocytopenia requiring renal replacement therapy.
abstract: BACKGROUND
  Argatroban, a direct thrombin inhibitor, is used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). The recommended initial dose is 2 microg/kg/min (0.5 microg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) values 1.5-3.0 times baseline. However, few argatroban-treated patients with HIT and renal failure requiring renal replacement therapy (RRT) have been described.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of argatroban anticoagulation during RRT in patients with HIT.
  
  
  METHODS
  We retrospectively reviewed records from 47 patients with HIT and renal failure requiring RRT who underwent 50 treatment courses with argatroban. Patients with HIT had received argatroban during prospective, multicenter studies. Outcomes, safety, and dosing information were summarized.
  
  
  RESULTS
  In the multicenter experience, no patient died due to thrombosis and 2 (4%) patients developed new thrombosis while on argatroban. No adverse outcomes occurred during argatroban reexposure. Starting doses were typically 2 microg/kg/min in patients without hepatic impairment and <1.5 microg/kg/min in those with hepatic impairment. Median (range) infusion doses were 1.7 (0.2-2.8) and 0.7 (0.1-1.7) microg/kg/min, respectively, with associated median (range) aPTT ratios, relative to baseline, of 2.2 (1.6-3.6) and 2.0 (1.4-4.1), respectively. Major bleeding occurred in 3 (6%) of 50 treatment courses.
  
  
  CONCLUSIONS
  Argatroban provides effective anticoagulation upon initial and repeated administration in patients with HIT and renal impairment requiring RRT, with an acceptably low bleeding risk. Current dosing recommendations are adequate for these patients.
authors.affiliation: Section of Nephrology, University of Chicago, IL 60637, USA. breddy@medicine.bsd.uchicago.edu
authors.forename: Bharathi V
authors.initials: BV
authors.lastname: Reddy
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Grossman
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Trevino
authors.forename: Marcie J
authors.initials: MJ
authors.lastname: Hursting
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Murray
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000379:methods*; D012189:Retrospective Studies; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban