Prostaglandin E1 potentiates the effects of P2Y12 blockade on ADP-mediated platelet aggregation in vitro: Insights using short thromboelastography

Platelets
Vikram KhannaN Curzen

Abstract

In addition to adenosine diphosphate (ADP), a number of platelet function tests including the VerifyNow P2Y12 assay (VN-P2Y12) employ prostaglandin E1 (PGE1) to improve specificity for P2Y12 blockade by mitigating the contribution of the P2Y1 pathway on ADP-mediated platelet aggregation. Using short thromboelastography (s-TEG), we have previously shown that VN-P2Y12 overestimates the functional effect of clopidogrel in some individuals. We investigated whether PGE1 systematically increases the inhibitory effects of P2Y12 blockade on ADP-mediated platelet aggregation in an in vitro model. Using s-TEG, we measured ADP-induced platelet aggregation either in the presence or absence of PGE1 (11 or 22 nM) in blood samples taken from healthy volunteers pre-incubated with prasugrel active metabolite (PAM; 0, 1, 3 or 10 µM). Individually, both PGE1 (p < 0.02) and PAM (p < 0.0001) inhibited ADP-mediated platelet aggregation in a dose-dependent manner, as expected. Furthermore, inclusion of PGE1 augmented inhibition of ADP-mediated platelet aggregation in response to PAM (p < 0.02) in a dose-dependent manner such that a 10-fold higher dose of PAM was required to attain equivalent inhibition of ADP-mediated platelet aggregation to that ach...Continue Reading

References

Jan 18, 2005·Journal of the American College of Cardiology·Victor L SerebruanyEric J Topol
Aug 30, 2008·The Journal of Biological Chemistry·Gianni F GuidettiMauro Torti
Nov 26, 2010·Prostaglandins & Other Lipid Mediators·David IyúStan Heptinstall
Jul 28, 2011·Purinergic Signalling·Béatrice Hechler, Christian Gachet
Nov 3, 2012·JAMA : the Journal of the American Medical Association·Paul A GurbelUNKNOWN TRILOGY ACS Platelet Function Substudy Investigators
Nov 6, 2012·The New England Journal of Medicine·Jean-Philippe ColletUNKNOWN ARCTIC Investigators
Sep 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nicholas S KirkbyTimothy D Warner
Oct 1, 2013·Journal of the American College of Cardiology·Udaya S TantryUNKNOWN Working Group on On-Treatment Platelet Reactivity

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