title: Extensive prolongation of aPTT with argatroban in an elderly patient with improving renal function, normal hepatic enzymes, and metastatic lung cancer.
abstract: OBJECTIVE
  To report a case of an elderly male with improving renal function and normal hepatic function who sustained an elevated activated partial thromboplastin time (aPTT) after an infusion of argatroban was discontinued.
  
  
  METHODS
  A 77-year-old white male with a history of heparin-induced thrombocytopenia (HIT) and metastatic lung disease was started on argatroban for treatment of a right upper-extremity deep vein thrombosis (DVT). The infusion was initiated at 2.0 microg/kg/min and was titrated to a goal aPTT of 60-80 seconds. Argatroban was discontinued due to an aPTT elevated to >100 seconds; the aPTT remained elevated for 130 hours after discontinuation of the infusion.
  
  
  CONCLUSIONS
  Argatroban dose reductions in patients with impaired liver and renal function test values have been reported. Elderly subjects may have a prolonged clearance compared with young healthy subjects, although the duration of effect has not been established. As of April 18, 2005, the effect of liver metastasis on argatroban pharmacokinetics in the setting of normal liver function enzyme levels has not been reported. An objective causality assessment using the Naranjo probability scale showed that the prolonged aPTT was probably attributable to argatroban.
  
  
  CONCLUSIONS
  Clinicians should exercise caution when initiating argatroban at a dose of 2.0 microg/kg/min in elderly patients with underlying comorbidities, such as metastatic disease and renal impairment, since this may lead to excessive and prolonged anticoagulation and increased risk of bleeding.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA 02115-6110, USA. dwkubiak@partners.org
authors.forename: David W
authors.initials: DW
authors.lastname: Kubiak
authors.forename: Paul M
authors.initials: PM
authors.lastname: Szumita
authors.forename: John R
authors.initials: JR
authors.lastname: Fanikos
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests / Q000379:methods; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008111:Liver Function Tests / Q000379:methods; D008175:Lung Neoplasms / Q000503:physiopathology / Q000556:secondary*; D008297:Male; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D013997:Time Factors; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban