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 (30mg/kg) or placebo, followed 4h later by saline or desmopressin (0.15, 0.3, or 0.6μg/kg). Bleeding times and platelet aggregation studies were subsequently performed. A bleeding time >25min was considered "prolonged." The median bleeding time for clopidogrel-exposed rats was 21min, vs. 6min 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 0.6μg/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 0.6μg/kg DDAVP. In this model of an ADP-receptor antagonist, DDAVP results in partial reversal of clopidogrel-induced platelet dysfunction.