title: The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count.
abstract: OBJECTIVE
  This study aimed to assess the association of clinical factors with P2Y12-dependent platelet inhibition as monitored by the ratio of ADP- to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively.
  
  
  BACKGROUND
  Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivo platelet inhibition.
  
  
  METHODS
  In a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP- to TRAP- induced aggregation reflecting the individual degree of P2Y12-mediated platelet reactivity.
  
  
  RESULTS
  Platelet aggregation was assessed in 359 patients. Means (± SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794 ± 239 AU*min, 297 ± 153 AU*min and 37 ± 14%, respectively. While ADP- and TRAP-induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302; p<0.001; TRAP: r = 0.509 p<0.001), r-ADP-agg values did not (r = -0.003; p = 0.960). These findings were unaltered in multivariate analyses adjusting for a range of factors potentially influencing platelet aggregation. The presence of an acute coronary syndrome and body weight were found to correlate with both ADP-induced platelet aggregation and r-ADP-agg.
  
  
  CONCLUSIONS
  The ratio of ADP- to TRAP-induced platelet aggregation quantifies P2Y12-dependent platelet inhibition independently of the platelet count in contrast to conventional ADP-induced aggregation. Furthermore, r-ADP-agg was associated with the presence of an acute coronary syndrome and body weight as well as ADP-induced aggregation. Thus, the r-ADP-agg is a more valid reflecting platelet aggregation and potentially prognosis after coronary stent-implantation in P2Y12-mediated HPR than conventional ADP-induced platelet aggregation.
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Christoph B
authors.initials: CB
authors.lastname: Olivier
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Munich University Hospital, Institute and Outpatient Clinic for Occupational, Social, and Environmental Medicine, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Bauer
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schnabel
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weik
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.affiliation: Heart Center Freiburg University, Cardiology and Angiology I, Freiburg-Bad Krozingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Diehl
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D009842:Oligopeptides; D058925:Receptors, Purinergic P2Y12; C096900:thrombin receptor-activating peptide SFLLRNPNDKY; D000244:Adenosine Diphosphate