title: Argatroban anticoagulation in intensive care patients: effects of heart failure and multiple organ system failure.
abstract: We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n=56) or history of heparin-induced thrombocytopenia (n=9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14+/-0.62 microg/kg/min (mean+/-SD) and administered for 11.4+/-9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58+/-0.28 vs 0.97+/-0.6 microg/kg/min, P= .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10+/-0.67 vs 0.87+/-0.47 vs 0.58+/-0.47 microg/kg/min, P= .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 micro/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.
authors.affiliation: Cleveland Clinic, Cleveland, Ohio, USA. begelman.susan@gene.com
authors.forename: Susan M
authors.initials: SM
authors.lastname: Begelman
authors.forename: Sarkis B
authors.initials: SB
authors.lastname: Baghdasarian
authors.forename: Inder M
authors.initials: IM
authors.lastname: Singh
authors.forename: Michael A
authors.initials: MA
authors.lastname: Militello
authors.forename: Marcie J
authors.initials: MJ
authors.lastname: Hursting
authors.forename: John R
authors.initials: JR
authors.lastname: Bartholomew
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D015331:Cohort Studies; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications* / Q000628:therapy; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications* / Q000628:therapy; D010875:Pipecolic Acids / Q000008:administration & dosage*; D012189:Retrospective Studies; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban