title: Reversal of thienopyridine-induced platelet dysfunction following desmopressin administration.
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.
authors.affiliation: Department of Emergency Medicine, Section of Medical Toxicology, University of Southern California, Los Angeles, CA, 90033, USA. Michael.Levine@bannerhealth.com
authors.forename: Michael
authors.initials: M
authors.lastname: Levine
authors.forename: Steve
authors.initials: S
authors.lastname: Swenson
authors.forename: Taylor
authors.initials: T
authors.lastname: McCormick
authors.forename: Sean O
authors.initials: SO
authors.lastname: Henderson
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Thomas
authors.forename: Francis S
authors.initials: FS
authors.lastname: Markland
mesh_terms: D000818:Animals; D050034:Antidiuretic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001760:Bleeding Time; D000077144:Clopidogrel; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000097:blood / Q000188:drug therapy*; D006490:Hemostatics / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000506:poisoning; D011355:Prodrugs / Q000506:poisoning*; D058921:Purinergic P2Y Receptor Antagonists / Q000506:poisoning*; D011725:Pyridines / Q000737:chemistry / Q000506:poisoning; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000506:poisoning
chemical_list: D050034:Antidiuretic Agents; D006490:Hemostatics; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D058921:Purinergic P2Y Receptor Antagonists; D011725:Pyridines; C446540:thienopyridine; D000077144:Clopidogrel; D003894:Deamino Arginine Vasopressin; D013988:Ticlopidine