title: Inhibition of the platelet P2Y12 receptor for adenosine diphosphate does not impair the capacity of platelet to synthesize thromboxane A2.
abstract: Patients with acute coronary syndromes (ACSs) are treated with acetylsalicylic acid (ASA) and antagonists of the P2Y12receptor (P2Y12R) for adenosine diphosphate (ADP). Based on the demonstration that P2Y12R antagonists inhibit thromboxane A2(TxA2) production (target of ASA), it was surmised that ACS patients might be treated with P2Y12R antagonists only. However, this demonstration contrasts with the results of previous studies. The aim of this study was to test whether P2Y12R antagonists have off-target/indirect inhibitory effects on platelet TxA2production.
  
  
  
  We studied 3 patients with inherited P2Y12R deficiency and 33 healthy subjects. Serum TxB2(TxA2metabolite) levels were similar in P2Y12R-deficient patients and healthy subjects and were not decreased by P2Y12R antagonists in vitro. Serum TxB2levels did not decrease in 20 patients treated with prasugrel (10 mg q.i.d.) or placebo for 14 days. Arachidonic acid- and collagen-induced platelet aggregation (PA) and TxB2production in platelet-rich plasma (PRP) of healthy subjects were inhibited in vitro by P2Y12R antagonists. However, P2Y12R antagonists did not inhibit TxB2production when PA was prevented by avoiding the stirring of PRP in the aggregometer. The P2Y1ADP-receptor antagonist MRS2500 had similar effects on PA and TxB2production as P2Y12R antagonists. Acetylsalicylic acid inhibited TxB2production more effectively than a P2Y12R antagonist; only the combination of ASA and a P2Y12R antagonist inhibited PA induced by high concentration of collagen.
  
  
  
  Inherited deficiency or pharmacological inhibition of P2Y12R does not affect the platelet capacity to synthesize TxA2. There is no pharmacological evidence that ACS patients may be safely treated with P2Y12R antagonists without ASA.
authors.affiliation: Dipartimento di Scienze Della Salute, Università Degli Studi di Milano, Milano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Scavone
authors.affiliation: Dipartimento di Scienze Della Salute, Università Degli Studi di Milano, Milano, Italy.
authors.forename: Eti Alessandra
authors.initials: EA
authors.lastname: Femia
authors.affiliation: Dipartimento di Scienze Della Salute, Università Degli Studi di Milano, Milano, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Caroppo
authors.affiliation: Dipartimento di Scienze Della Salute, Università Degli Studi di Milano, Milano, Italy marco.cattaneo@unimi.it.|Unità di Medicina 3, Azienda Ospedaliera San Paolo, Via di Rudinì, 8, 20142 Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
mesh_terms: D000244:Adenosine Diphosphate; D001241:Aspirin; D001792:Blood Platelets; D006801:Humans; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013928:Thromboxane A2
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D001241:Aspirin
keywords: Antiplatelet drugs; Aspirin; Myocardial infarction; P2Y12 receptor; Platelet aggregation; Thromboxane A2