title: Impact of aspirin dose on adenosine diphosphate-mediated platelet activities. Results of an in vitro pilot investigation.
abstract: Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (p<0.001). However, there were no differences according to aspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 μM: p=0.888; 3 μM: p=0.524; 10 μM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators.
authors.affiliation: Dominick J. Angiolillo, MD, PhD, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA, Tel: +1 904 244 3933, Fax: +1 904 244 3102, E-mail: dominick.angiolillo@jax.ufl.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Estela
authors.initials: E
authors.lastname: Thano
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Ronakkumar
authors.initials: R
authors.lastname: Patel
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wilson
authors.forename: Ana
authors.initials: A
authors.lastname: Muñiz-Lozano
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010865:Pilot Projects; D010879:Piperazines / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000068799:Prasugrel Hydrochloride; D001241:Aspirin
keywords: Aspirin; platelet function; purinergic pathway