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Excessive Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia

Pharmacy Clinical Coordinator — Surgery, Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC

Drew A MacGregor, MD

Associate Professor, Department of Anesthesiology and Internal Medicine, School of Medicine, Wake Forest University

Edward H Kincaid, MD

Assistant Professor, Department of Cardiothoracic Surgery, School of Medicine, Wake Forest University

Sylvia Y Dolinski, MD FCCP

Assistant Professor, Department of Anesthesiology, School of Medicine, Wake Forest University

Reprints: Marc G Reichert PharmD BCPS, Department of Pharmacy, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1163, FAX 336/713-3401, E-mail reichert{at}wfubmc.edu

OBJECTIVE: To report 4 patients who became excessively anticoagulated with the recommended or lower starting doses of argatroban during treatment for heparin-induced thrombocytopenia type II (HIT-II) in a cardiothoracic intensive care unit.

CASE SUMMARY: Four patients were treated with argatroban after confirmation of HIT-II after cardiac surgery. In 3 patients, argatroban was initiated at the recommended starting dose of 2 µg/kg/min; in 1 patient, therapy was initiated at 1 µg/kg/min. All patients had relatively normal hepatic function. In all cases, the resulting activated partial thromboplastin time was supertherapeutic and exceeded 100 seconds in 3 patients. Additionally, argatroban clearance appeared to be prolonged upon discontinuation.

DISCUSSION: Argatroban pharmacokinetics in critically ill patients have not been investigated. Our case series demonstrates the potential over-anticoagulation that can occur in this patient population despite relatively normal hepatic function. An objective causality assessment revealed that the adverse drug event in these patients was probably caused by administration of argatroban.

CONCLUSIONS: Formal pharmacokinetic studies of argatroban are needed in critically ill patients in order to optimize therapy.

Key Words: argatroban, cardiac surgery, heparin-induced thrombocytopenia

Published Online, March 25, 2003. www.theannals.com, DOI 10.1345/aph.1C187

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