Journal of Medical Toxicology

, Volume 9, Issue 2, pp 139–143

Reversal of Thienopyridine-Induced Platelet Dysfunction Following Desmopressin Administration

  • Michael Levine
  • Steve Swenson
  • Taylor McCormick
  • Sean O. Henderson
  • Stephen H. Thomas
  • Francis S. Markland
Toxicology Investigation

DOI: 10.1007/s13181-012-0275-6

Cite this article as:
Levine, M., Swenson, S., McCormick, T. et al. J. Med. Toxicol. (2013) 9: 139. doi:10.1007/s13181-012-0275-6
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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.

Keywords

Clopidogrel DDAVP Desmopressin Bleeding Overdose 

Copyright information

© American College of Medical Toxicology 2012

Authors and Affiliations

  • Michael Levine
    • 1
  • Steve Swenson
    • 2
  • Taylor McCormick
    • 3
  • Sean O. Henderson
    • 3
  • Stephen H. Thomas
    • 4
  • Francis S. Markland
    • 2
  1. 1.Department of Emergency Medicine, Section of Medical ToxicologyUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of Biochemistry and Molecular Biology and the Norris Comprehensive Cancer Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Emergency MedicineUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Department of Emergency MedicineUniversity of Oklahoma School of Community MedicineTulsaUSA