Excessive Argatroban Anticoagulation for Heparin-Induced Thrombocytopenia

Author:

Reichert Marc G1,MacGregorew A2,Kincaid Edward H3,Dolinski Sylvia Y4

Affiliation:

1. Marc G Reichert PharmD BCPS, Pharmacy Clinical Coordinator — Surgery, Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC

2. Drew A MacGregor MD, Associate Professor, Department of Anesthesiology and Internal Medicine, School of Medicine, Wake Forest University

3. Edward H Kincaid MD, Assistant Professor, Department of Cardiothoracic Surgery, School of Medicine, Wake Forest University

4. Sylvia Y Dolinski MD FCCP, Assistant Professor, Department of Anesthesiology, School of Medicine, Wake Forest University

Abstract

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.

Publisher

SAGE Publications

Subject

Pharmacology (medical)

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2. Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review;Journal of Intensive Care Medicine;2021-03-03

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4. Risk Factors and Outcomes Associated with Prolonged Subtherapeutic Anticoagulation with Bivalirudin: A Retrospective Cohort Study;Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy;2019-10-29

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