title: Argatroban therapy for heparin-induced thrombocytopenia in acutely ill patients.
abstract: Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. To evaluate clinical outcomes and effects of argatroban therapy in acutely ill HIT patients. Retrospective analysis. Hospital in-patient. Acutely ill patients with clinically diagnosed HIT from previous multicenter, historically controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times 1.5 to 3 times baseline, or historical control therapy (ie, no direct thrombin inhibition). We identified 488 patients who received argatroban (N = 390; mean dose of 1.9 microg/kg/min for a mean 6 days) or historical control therapy (N = 98) for HIT. The primary all-cause composite endpoint of death, amputation, or new thrombosis within 37 days occurred in 133 (34.1%) argatroban-treated patients and 38 (38.8%) controls (P = .41). Argatroban, versus control, significantly reduced the primary thrombosis-related composite endpoint of death because of thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis (17.7% vs 30.6%, P = .007). Significant reductions also occurred in new thrombosis and death because of thrombosis. Major bleeding was similar between groups (7.7% vs 8.2%; P = .84). Adverse outcomes were more likely to occur in patients who were initially diagnosed with HIT and thrombosis, had undergone cardiac surgery, were not white, or had more severe thrombocytopenia. In acutely ill HIT patients, argatroban, versus historical control, provides effective antithrombotic therapy without increasing major bleeding. Patients with more severe thrombocytopenia or HIT-related thrombosis on HIT diagnosis have a poorer prognosis, emphasizing the importance of prompt recognition/ treatment of HIT in acutely ill patients.
authors.affiliation: Department of Pulmonary Medicine, Lahey Clinic, Burlington, Massachusetts 01805, USA. anthony.w.gray@lahey.org
authors.forename: Anthony
authors.initials: A
authors.lastname: Gray
authors.forename: Diane E
authors.initials: DE
authors.lastname: Wallis
authors.forename: Marcie J
authors.initials: MJ
authors.lastname: Hursting
authors.forename: Eliezer
authors.initials: E
authors.lastname: Katz
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Lewis
mesh_terms: D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects; D001120:Arginine / Q000031:analogs & derivatives; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010976:Platelet Count; D012189:Retrospective Studies; D012449:Safety; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban