title: Argatroban therapy for heparin-induced thrombocytopenia in ICU patients with multiple organ dysfunction syndrome: a retrospective study.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated adverse reaction triggered by heparin therapy. When HIT is diagnosed or suspected, heparins should be discontinued, and an alternative, fast-acting, parenteral, nonheparin anticoagulation such as argatroban should be initiated. Limited and inconsistent data exist about dosing of argatroban in intensive care unit (ICU) patients with critical illnesses.
  
  
  METHODS
  Retrospective analysis of 12 ICU patients with multiple organ dysfunction syndrome (MODS) treated with argatroban for suspected or diagnosed HIT.
  
  
  RESULTS
  The 12 ICU patients with a mean platelet count of 46,000 +/- 30,310 had a mean APACHE II score of 26.7 +/- 7.8 on ICU admission and a mean SAPS II score of 61.5 +/- 16.3 on the first day of argatroban administration. A mean argatroban starting dose of 0.32 +/- 0.25 microg/kg/min (min, 0.04; max, 0.83) was used to achieve activated partial thromboplastin times (aPTTs) >60 sec or aPTTs of 1.5 to 3 times the baseline aPTT. Adjustment to aPTT required dose reduction in six (50%) patients. Patients were treated for a mean of 5.5 +/- 3.3 days. The final mean dose in these critically ill patients was 0.24 +/- 0.16 microg/kg/min, which is about one eighth of the usually recommended dose and even markedly lower than the previously suggested dose for critically ill ICU patients. In all patients, desired levels of anticoagulation were achieved. The mean argatroban dose was significantly lower in patients with hepatic insufficiency compared with patients without hepatic impairment (0.10 +/- 0.06 microg/kg/min versus 0.31 +/- 0.14 microg/kg/min; P = 0.026). The mean argatroban dose was significantly correlated with serum bilirubin (r = -0.739; P = 0.006).
  
  
  CONCLUSIONS
  ICU Patients with MODS and HIT can be effectively treated with argatroban. A decrease in the initial dosage is mandatory in this patient population. Further studies are needed to investigate argatroban elimination and dosage adjustments for critically ill patients.
authors.affiliation: II Medizinische Klinik, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr 22, 81675 München, Germany. bernd.saugel@lrz.tu-muenchen.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Saugel
authors.forename: Veit
authors.initials: V
authors.lastname: Phillip
authors.forename: Georg
authors.initials: G
authors.lastname: Moessmer
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000378:metabolism; D000991:Antithrombins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D013449:Sulfonamides; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban