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Reversal of Thienopyridine-Induced Platelet Dysfunction Following Desmopressin Administration

  • Toxicology Investigation
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An Erratum to this article was published on 04 June 2014

Abstract

Adenosine diphosphate (ADP)-receptor antagonists are widely used for thrombus prevention, although reversing their platelet dysfunction is difficult. This study evaluated the ability of desmopressin to reverse clopidogrel-induced platelet dysfunction. Sprague–Dawley rats received either clopidogrel (30 mg/kg) or placebo, followed 4 h later by saline or desmopressin (0.15, 0.3, or 0.6 μg/kg). Bleeding times and platelet aggregation studies were subsequently performed. A bleeding time >25 min was considered “prolonged.” The median bleeding time for clopidogrel-exposed rats was 21 min, vs. 6 min for controls (p < 0.01). Progressively higher doses of 1-deamino-8-d-arginine vasopressin (DDAVP) were associated with a reduced number of rats with prolonged bleeding time (p = 0.001). Higher doses of DDAVP were also associated with a reduction in the median (IQR) bleeding time; 29 (13.5–30) min in rats receiving clopidogrel without DDAVP vs. 19 (12–28) min in rats receiving clopidogrel and 0.6 μg/kg DDAVP. The step-wise dosing of DDAVP resulted in a 54 % reduction in meeting the endpoint of prolonged bleeding time (OR 0.46; p = 0.025; 95 % CI 0.23–0.91). Platelet aggregation was observed in all control rats, but only some of those clopidogrel-treated rats who received 0.6 μg/kg DDAVP. In this model of an ADP-receptor antagonist, DDAVP results in partial reversal of clopidogrel-induced platelet dysfunction.

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Conflicts of Interest

There are no financial, litigious, or other conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Emergency Medicine, Section of Medical Toxicology, University of Southern California, 1200 North State Street, Room 1011, Los Angeles, CA, 90033, USA

    Michael Levine

  2. Department of Biochemistry and Molecular Biology and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Steve Swenson & Francis S. Markland

  3. Department of Emergency Medicine, University of Southern California, Los Angeles, CA, USA

    Taylor McCormick & Sean O. Henderson

  4. Department of Emergency Medicine, University of Oklahoma School of Community Medicine, Tulsa, OK, USA

    Stephen H. Thomas

Authors
  1. Michael Levine
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  2. Steve Swenson
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  3. Taylor McCormick
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  4. Sean O. Henderson
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  5. Stephen H. Thomas
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  6. Francis S. Markland
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Correspondence to Michael Levine.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s13181-013-0308-9.

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Levine, M., Swenson, S., McCormick, T. et al. Reversal of Thienopyridine-Induced Platelet Dysfunction Following Desmopressin Administration. J. Med. Toxicol. 9, 139–143 (2013). https://doi.org/10.1007/s13181-012-0275-6

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  • DOI: https://doi.org/10.1007/s13181-012-0275-6

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