Patients with acute coronary syndromes (ACS) are treated with dual antiplatelet therapy (DAPT), which includes aspirin, an inhibitor of thromboxane A2 (TxA2) production, and an antagonist of the P2Y12 receptor for ADP. Based on the recent observation that P2Y12 antagonists also inhibit the platelet production of TxA2, it has been suggested that patients with ACS might be safely treated with P2Y12 antagonists only. However, the observation that platelets congenitally deficient of P2Y12 synthesize normal amounts of TxA2 contrasts the results obtained with P2Y12 antagonists. To test whether the reported inhibitory effect of P2Y12 antagonists on TxA2 production is due to off-target effects, or secondary to inhibition of platelet aggregation (PA). Serum TxB2 was measured in 2 patients with inherited P2Y12 deficiency and 7 healthy subjects in presence/absence of increasing concentrations of P2Y12 antagonists added in vitro, and in 20 patients treated with 10 mg/d prasugrel (P2Y12 antagonist) or placebo for 14 days in a randomized, double-blind, cross-over study. TxB2 levels were also measured after stimulation of citrate-PRP by collagen (0,5µg/mL) or arachidonic acid (1mM) in an aggregometer in presence/absence of P2Y12 antagonists, under stirring and non-stirring conditions (PA does not occur without stirring). P2Y12 antagonists did not decrease serum TxB2 levels both in vitro and ex vivo (prasugrel-treated patients). They partially inhibited TxB2 production under stirring, but not under non-stirring conditions. In conclusion, P2Y12 antagonists do not inhibit the platelet TxA2 production; therefore, there is no pharmacological evidence that aspirin should be withheld in patients with ACS.
DOES THE INHIBITION OF P2Y12 INHIBIT THE PRODUCTION OF THROMBOXANE A2 BY PLATELETS? / M. Scavone ; tutor: M.N. Cattaneo ; coordinatore: M.N. Cattaneo. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE DELLA SALUTE, 2014 Mar 25. ((26. ciclo, Anno Accademico 2013.
|Titolo:||DOES THE INHIBITION OF P2Y12 INHIBIT THE PRODUCTION OF THROMBOXANE A2 BY PLATELETS?|
|Supervisori e coordinatori interni:||CATTANEO, MARCO NATALE|
|Data di pubblicazione:||25-mar-2014|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Citazione:||DOES THE INHIBITION OF P2Y12 INHIBIT THE PRODUCTION OF THROMBOXANE A2 BY PLATELETS? / M. Scavone ; tutor: M.N. Cattaneo ; coordinatore: M.N. Cattaneo. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE DELLA SALUTE, 2014 Mar 25. ((26. ciclo, Anno Accademico 2013.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/scavone-mariangela_phd2014-03-25|
|Appare nelle tipologie:||Tesi di dottorato|