Platelet transfusion reverses bleeding evoked by triple anti-platelet therapy including vorapaxar, a novel platelet thrombin receptor antagonist

Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antip...

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Bibliographic Details
Published in:European journal of pharmacology 2015-07, Vol.758, p.107-114
Main Authors: Cai, Tian-Quan, Wickham, L. Alexandra, Sitko, Gary, Michener, Maria Strainer, Raubertas, Richard, Handt, Larry, Chintala, Madhu, Seiffert, Dietmar, Forrest, Michael
Format: Article
Language:English
Subjects:
Animals
Aspirin
Aspirin - administration & dosage
Aspirin - adverse effects
Bleeding Time
Blood platelets
Clopidogrel
Drug Therapy, Combination - adverse effects
Hemorrhage
Hemorrhage - chemically induced
Hemorrhage - therapy
Humans
Lactones - administration & dosage
Lactones - adverse effects
Macaca fascicularis
Platelet Aggregation Inhibitors - administration & dosage
Platelet Aggregation Inhibitors - adverse effects
Platelet Transfusion
Pyridines - administration & dosage
Pyridines - adverse effects
Receptors, Thrombin - antagonists & inhibitors
Ticlopidine - administration & dosage
Ticlopidine - adverse effects
Ticlopidine - analogs & derivatives
Vorapaxar
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Summary:Vorapaxar is a novel protease-activated receptor-1 (PAR-1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Patients who received vorapaxar in addition to standard of care antiplatelet therapy had an increased incidence of major bleeding events compared with placebo. To assess whether platelet transfusion can restore hemostasis in primates on triple antiplatelet therapy, template bleeding times were assessed concurrently in the buccal mucosa, finger pad, and distolateral tail of anesthetized cynomolgus macaques to evaluate bleeding with vorapaxar as either monotherapy or in combination with aspirin or aspirin and clopidogrel. Aspirin (5mg/kg, IV) or vorapaxar (1mg/kg, PO) alone had no significant effect on bleeding times in the three vascular beds examined. A modest (
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2015.03.073