title: Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.
abstract: OBJECTIVE
  Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo.
  
  
  RESULTS
  We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function.
  
  
  CONCLUSIONS
  Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.
authors.affiliation: Thrombosis Center, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy. loredana.mendolicchio@humanitas.it
authors.forename: G L
authors.initials: GL
authors.lastname: Mendolicchio
authors.forename: D
authors.initials: D
authors.lastname: Zavalloni
authors.forename: M
authors.initials: M
authors.lastname: Bacci
authors.forename: E
authors.initials: E
authors.lastname: Corrada
authors.forename: M
authors.initials: M
authors.lastname: Marconi
authors.forename: C
authors.initials: C
authors.lastname: Lodigiani
authors.forename: P
authors.initials: P
authors.lastname: Presbitero
authors.forename: L
authors.initials: L
authors.lastname: Rota
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ruggeri
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000166:cytology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects*; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12