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Thromb Haemost 2013; 110(04): 777-784
DOI: 10.1160/TH13-05-0400
Platelets and Blood Cells
Schattauer GmbH

Impact of aspirin dose on adenosine diphosphate-mediated platelet activities

Results of an in vitro pilot investigation
Antonio Tello-Montoliu
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Estela Thano
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Fabiana Rollini
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Ronakkumar Patel
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Ryan E. Wilson
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Ana Muñiz-Lozano
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Francesco Franchi
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Andrew Darlington
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Bhaloo Desai
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Luis A. Guzman
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Theodore A. Bass
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Dominick J. Angiolillo
1   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
› Author Affiliations
Further Information

Publication History

Received: 18 May 2013

Accepted after major revision: 02 July 2013

Publication Date:
01 December 2017 (online)

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Summary

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 ïM: p=0.888; 3 ïM: p=0.524; 10 ïM: 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.

Keywords

Aspirin - platelet function - purinergic pathway
 

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