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NEPHROLOGY

Argatroban and Renal Replacement Therapy in Patients with Heparin-Induced Thrombocytopenia

Fellow in Nephrology and Clinical Pharmacology, Section of Nephrology, Department of Medicine, University of Chicago Hospitals, Chicago, IL

Donna S Cox, PhD

Senior Clinical Pharmacokineticist, Clinical Pharmacokinetics/Modeling and Simulation, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, King of Prussia, PA

Kruti Patel, BA

Clinical Research Assistant, Section of Nephrology, Department of Medicine, University of Chicago Hospitals

Bharathi V Reddy, MD

Assistant Professor of Medicine, Section of Nephrology, Department of Medicine, University of Chicago Hospitals

Linda Nahlik, BS

Clinical Pharmacy Specialist, Director of Anticoagulation Services, Department of Pharmaceutical Services, University of Chicago Hospitals

Sharon Trevino, BS RN

Research Coordinator, Section of Nephrology, Department of Medicine, University of Chicago Hospitals

Patrick T Murray, MD

Associate Professor of Medicine, Section of Nephrology, Department of Medicine, University of Chicago Hospitals

Reprints: Dr. Tang, Section of Nephrology, Department of Medicine, University of Chicago Hospitals, 5841 S. Maryland Ave., MC5100, Chicago, IL 60637-1470, fax 773/702-5818, itang{at}medicine.bsd.uchicago.edu

BACKGROUND: Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT).

OBJECTIVE: To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT.

METHODS: Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5–2 µg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated.

RESULTS: Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean ± SD values of 74.3 ± 34.2 seconds, 198 ± 23 seconds, and 499 ± 353 ng/mL before RRT, and 70.6 ± 21.4 seconds, 181 ± 12 seconds, and 453 ± 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 ± 12.8 L/h before hemodialysis and 17.0 ± 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 ± 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred.

CONCLUSIONS: Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Key Words: argatroban, dialysis, heparin-induced platelet aggregation, renal replacement therapy, thrombocytopenia

Published Online, January 4, 2005. www.theannals.com, DOI 10.1345/aph.1E480

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