title: Platelet function normalization after a prasugrel loading-dose: time-dependent effect of platelet supplementation.
abstract: BACKGROUND
  Hemostatic benefits of platelet transfusions in thienopyridine-treated acute coronary syndrome (ACS) patients may be compromised by residual metabolite in circulation.
  
  
  OBJECTIVE
  To estimate the earliest time after a prasugrel loading-dose when added platelets are no longer inhibited by prasugrel's active metabolite.
  
  
  METHODS
  Baseline platelet reactivity of healthy subjects (n=25, 30 ± 5 years, 68% male) on ASA 325 mg was tested using maximum platelet aggregation (MPA, ADP 20 μm) and VerifyNow(®) P2Y12 and was followed by a 60 mg prasugrel loading-dose. At 2, 6, 12 and 24 h post-dose, fresh concentrated platelets from untreated donors were added ex-vivo to subjects' blood, raising platelet counts by 0% (control), 40%, 60% and 80%. To estimate the earliest time when prasugrel's active metabolite's inhibitory effect on the added platelets ceases, platelet function in supplemented samples was compared across time-points to identify the time when effect of supplementation on platelet function stabilized (i.e. the increase in platelet reactivity was statistically similar to that at the next time-point).
  
  
  RESULTS
  Supplemented samples showed concentration-dependent increases in platelet reactivity vs. respective controls by both MPA and VerifyNow(®) at all assessment time-points. For each supplementation level, platelet reactivity showed a sharp increase from 2 to 6 h but was stable (P=NS) between 6 and 12 h.
  
  
  CONCLUSIONS
  The earliest measured time when supplemented platelets were not inhibited by circulating active metabolite of prasugrel was 6 h after a prasugrel loading-dose. These findings may have important implications for prasugrel-treated ACS patients requiring platelet transfusions during surgery.
authors.affiliation: Mount Sinai School of Medicine, New York, NY             Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: M U
authors.initials: MU
authors.lastname: Zafar
authors.forename: C
authors.initials: C
authors.lastname: Santos-Gallego
authors.forename: D A
authors.initials: DA
authors.lastname: Vorchheimer
authors.forename: J F
authors.initials: JF
authors.lastname: Viles-Gonzalez
authors.forename: S
authors.initials: S
authors.lastname: Elmariah
authors.forename: C
authors.initials: C
authors.lastname: Giannarelli
authors.forename: S
authors.initials: S
authors.lastname: Sartori
authors.forename: D S
authors.initials: DS
authors.lastname: Small
authors.forename: J A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010976:Platelet Count; D017713:Platelet Transfusion; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D013876:Thiophenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride; D001241:Aspirin