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1 Assistant Professor of Medicine, Section of Nephrology, University of Chicago,
Chicago, IL
2 Medical Student, University of Chicago
3 Research Nurse, Section of Nephrology, University of Chicago
4 Director, Clinical Science Consulting, Potomac, MD
5 Associate Professor of Medicine, Anesthesia and Critical Care, and the
Committee on Clinical Pharmacology, University of Chicago
Reprints: Dr. Reddy, University of Chicago, 5841 S. Maryland Ave., S511, MC5100, Chicago, IL 60637-1447, fax 773/702-5818, breddy{at}medicine.bsd.uchicago.edu
BACKGROUND: Argatroban, a direct thrombin inhibitor, is used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). The recommended initial dose is 2 µg/kg/min (0.5 µg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) values 1.5-3.0 times baseline. However, few argatroban-treated patients with HIT and renal failure requiring renal replacement therapy (RRT) have been described.
OBJECTIVE: To evaluate the safety and efficacy of argatroban anticoagulation during RRT in patients with HIT.
METHODS: We retrospectively reviewed records from 47 patients with HIT and renal failure requiring RRT who underwent 50 treatment courses with argatroban. Patients with HIT had received argatroban during prospective, multicenter studies. Outcomes, safety, and dosing information were summarized.
RESULTS: In the multicenter experience, no patient died due to thrombosis and 2 (4%) patients developed new thrombosis while on argatroban. No adverse outcomes occurred during argatroban reexposure. Starting doses were typically 2 µg/kg/min in patients without hepatic impairment and <1.5 µg/kg/min in those with hepatic impairment. Median (range) infusion doses were 1.7 (0.2-2.8) and 0.7 (0.1-1.7) µg/kg/min, respectively, with associated median (range) aPTT ratios, relative to baseline, of 2.2 (1.6-3.6) and 2.0 (1.4-4.1), respectively. Major bleeding occurred in 3 (6%) of 50 treatment courses.
CONCLUSIONS: Argatroban provides effective anticoagulation upon initial and repeated administration in patients with HIT and renal impairment requiring RRT, with an acceptably low bleeding risk. Current dosing recommendations are adequate for these patients.
Key Words: anticoagulation, argatroban, dialysis, renal replacement therapy
Published Online, August 30, 2005. www.theannals.com, DOI 10.1345/aph.1G033
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