title: Response to prasugrel and levels of circulating reticulated platelets in patients with ST-segment elevation myocardial infarction.
abstract: OBJECTIVE
  The aim of this study was to determine whether response to prasugrel is associated with the proportion of circulating reticulated platelets (RPs) in patients with ST-segment elevation myocardial infarction (STEMI).
  
  
  BACKGROUND
  Despite better pharmacodynamic properties and clinical efficacy of prasugrel compared with clopidogrel, antiplatelet responses to prasugrel are not uniform. The mechanism of this variability in response is not clear. RPs, young hyperactive forms, are increased during situations of enhanced platelet turnover.
  
  
  METHODS
  Patients with STEMI treated with primary percutaneous intervention (PCI) and prasugrel were tested for platelet reactivity using purinergic receptor P₂Y, G-protein coupled, 12 (P₂Y₁₂) assay and multiple electrode aggregometry (MEA). RP levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2 to 4 days and 30 days post-PCI. Platelet function was compared by varying levels of RPs, analyzed as continuous (regression analysis) and categorical (tertiles) variables.
  
  
  RESULTS
  Sixty-two patients were included (mean age: 57.5 ± 8 years; 21.2% women; 27.7% diabetes). At the early time point, RP levels were strongly correlated with platelet reactivity when evaluated by the P₂Y₁₂ assay (Spearman's correlation coefficient: 0.55 for P₂Y₁₂ reaction units, -0.49 for percent inhibition) and MEA (Spearman's: 0.50). The upper tertile of RPs displayed higher platelet reactivity compared with the middle and lower tertiles, according to P₂Y₁₂ assay and MEA. Similar results with strong correlations between RP and platelet reactivity were noted at 30 days post-PCI.
  
  
  CONCLUSIONS
  The proportion of circulating RPs strongly correlates with response to prasugrel in patients with STEMI treated with PCI. High levels of RPs are associated with increased platelet reactivity despite prasugrel treatment.
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Leor
authors.initials: L
authors.lastname: Perl
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Clinical Pharmacy Department, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Lerman-Shivek
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Eldad
authors.initials: E
authors.lastname: Rechavia
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: The Felsenstein Medical Research Institute, Rabin Medical Center, Petah-Tikva, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Leshem-Lev
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Zemer-Wassercug
authors.affiliation: The Felsenstein Medical Research Institute, Rabin Medical Center, Petah-Tikva, Israel.
authors.forename: Oshrat
authors.initials: O
authors.lastname: Dadush
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Pablo
authors.initials: P
authors.lastname: Codner
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Tamir
authors.initials: T
authors.lastname: Bental
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Battler
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
authors.affiliation: Cardiology Department, Rabin Medical Center, Petah-Tikva, Israel, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: elil@clalit.org.il.
authors.forename: Eli I
authors.initials: EI
authors.lastname: Lev
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride
keywords: ST-segment elevation myocardial infarction; antiplatelet therapy; pharmacology