title: Excessive argatroban anticoagulation for heparin-induced thrombocytopenia.
abstract: OBJECTIVE
  To report 4 patients who became excessively anticoagulated with the recommended or lower starting doses of argatroban during treatment for heparin-induced thrombocytopenia type II (HIT-II) in a cardiothoracic intensive care unit.
  
  
  METHODS
  Four patients were treated with argatroban after confirmation of HIT-II after cardiac surgery. In 3 patients, argatroban was initiated at the recommended starting dose of 2 micro g/kg/min; in 1 patient, therapy was initiated at 1 micro g/kg/min. All patients had relatively normal hepatic function. In all cases, the resulting activated partial thromboplastin time was supertherapeutic and exceeded 100 seconds in 3 patients. Additionally, argatroban clearance appeared to be prolonged upon discontinuation.
  
  
  CONCLUSIONS
  Argatroban pharmacokinetics in critically ill patients have not been investigated. Our case series demonstrates the potential over-anticoagulation that can occur in this patient population despite relatively normal hepatic function. An objective causality assessment revealed that the adverse drug event in these patients was probably caused by administration of argatroban.
  
  
  CONCLUSIONS
  Formal pharmacokinetic studies of argatroban are needed in critically ill patients in order to optimize therapy.
authors.affiliation: Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157-1163, USA. reichert@wfubmc.edu
authors.forename: Marc G
authors.initials: MG
authors.lastname: Reichert
authors.forename: Drew A
authors.initials: DA
authors.lastname: MacGregor
authors.forename: Edward H
authors.initials: EH
authors.lastname: Kincaid
authors.forename: Sylvia Y
authors.initials: SY
authors.lastname: Dolinski
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D001120:Arginine / Q000031:analogs & derivatives; D016638:Critical Illness; D062787:Drug Overdose; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban