title: Impact of immature platelets on platelet response to ticagrelor and prasugrel in patients with acute coronary syndrome.
abstract: OBJECTIVE
  The influence of reticulated platelets (RPs) on platelet inhibition by ticagrelor when compared with prasugrel is unknown. We aimed to determine the influence of RPs on adenosine diphosphate- (ADP-) induced platelet aggregation in patients with acute coronary syndrome who were randomly assigned to receive either ticagrelor or prasugrel for P2Y12 receptor inhibition.
  
  
  RESULTS
  One hundred and twenty-four patients were prospectively enrolled. The immature platelet fraction (IPF) was measured by an automated haematoanalyzer and platelet aggregation was assessed by multiple electrode aggregometry. In a subgroup of patients (n = 28) ADP-induced P-selectin expression was measured in dependence of the time point of study drug intake in RPs that were discriminated from mature platelets by thiazole-orange (TO) staining. The primary endpoint was the correlation of platelet aggregation and IPF in ticagrelor- vs. prasugrel-treated patients. Platelet aggregation significantly correlated with IPF in patients who received prasugrel (r = 0.41, P < 0.001). In contrast, no correlation between IPF and platelet aggregation was observed in ticagrelor-treated patients (r = 0.08, P = 0.51, P for difference of correlation coefficients P = 0.05). Within the TO-positive RP fraction, P-selectin expression was significantly higher in prasugrel when compared with ticagrelor-treated individuals (prasugrel 18.6 ± 16.0% vs. ticagrelor 11.5 ± 6.0%, P = 0.047). A time-dependent P-selectin expression was observed in prasugrel but not in ticagrelor-treated patients (prasugrel early 11.9 ± 9.4% vs. late 26.3 ± 19.0%, P = 0.031, ticagrelor early 9.6 ± 4.9% vs. late 13.5 ± 6.6%, P = 0.127).
  
  
  CONCLUSIONS
  Reticulated platelets show a greater impact on platelet reactivity in response to prasugrel when compared with ticagrelor.
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany isabell.bernlochner@tum.de.
authors.forename: Isabell
authors.initials: I
authors.lastname: Bernlochner
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goedel
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Conny
authors.initials: C
authors.lastname: Plischke
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schüpke
authors.affiliation: Institute for Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Institute for Clinical Chemistry, Technische Universität München, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Morath
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.affiliation: Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Siess
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D000077486:Ticagrelor; D016896:Treatment Outcome
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine
keywords: Acute coronary syndrome; Platelet aggregation; Prasugrel; Reticulated platelets; Ticagrelor