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Medical Director, Cardiac Surgical Intensive Care Unit, Division of Cardiac Surgery, Massachusetts General Hospital, Boston, MA
at time of study, Pharmacy Resident, Department of Pharmacy, Massachusetts General Hospital; now, Clinical Pharmacist, Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD
Assistant Director of Biostatistics, CTI Clinical Trial and Consulting Services, Cincinnati, OH
Clinical Scientist, Clinical Science Consulting, Austin, TX
Reprints: Dr. Hursting, Clinical Science Consulting, 3001 Loveland Cove, Austin, TX 78746, fax 512/329-9661, mhursting{at}sprintmail.com
BACKGROUND: The Food and Drug Administration-approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 µg/kg/min (0.5 µg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5-3 times baseline. Recent data suggest that reduced doses are required after cardiovascular surgery.
OBJECTIVE: To characterize dosing requirements, aPTTs, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft (CABG) surgery.
METHODS: Charts of 39 patients who underwent CABG surgery and were administered argatroban postoperatively for laboratory-confirmed HIT (n = 25), antibody-negative suspected HIT (n = 10), or previous HIT requiring anticoagulation (n = 4) were retrospectively reviewed. Patient characteristics, argatroban dosing information, aPTTs (target range 45-90 sec), and outcomes were summarized. Regression analyses explored potential effectors of dosage.
RESULTS: Patient features, argatroban dosing patterns, and aPTTs were similar among groups. Many patients had laboratory evidence of some hepatic and/or renal dysfunction (median [range] bilirubin 1.0 [0.3-8.0] mg/dL, creatinine clearance 47 [18-287] mL/min). Overall, median argatroban doses were 0.5 µg/kg/min initially and 0.6 µg/kg/min during therapy (median duration 5.3 days). After argatroban initiation, aPTTs were greater than 90 seconds at first assessment in 4 patients (3 with abnormal hepatic function test results) initially administered 0.5, 1, 2, and 2 µg/kg/min, respectively. Within approximately 16 hours of therapy, 33 (85%) patients achieved consecutive therapeutic aPTTs. No association was detected between mean dose during therapy and preoperative ejection fraction, routine hepatic or renal function test results (other than blood urea nitrogen [BUN]), or surgery type. A clinically insignificant association existed between dose and BUN: there was an approximately 0.15 µg/kg/min dose decrease for each 10 mg/dL BUN increase. One patient developed thrombosis, 1 underwent finger amputation, 7 died (5 after argatroban cessation), and 4 had significant bleeding.
CONCLUSIONS: These findings suggest that reduced initial argatroban doses (eg, 0.5 µg/kg/min), adjusted to achieve therapeutic aPTTs, provide rapid, adequate anticoagulation in postoperative CABG patients with presumed or previous HIT. Prospective study of reduced initial dosing in this setting is warranted.
Key Words: argatroban, coronary artery bypass graft, heparin-induced thrombocytopenia
Published Online, February 26, 2008. www.theannals.com, DOI 10.1345/aph.1K434
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