title: The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists'-inducible platelet reactivity.
abstract: BACKGROUND
  Circulating monocyte-platelet aggregates (MPA) are a sensitive marker of in vivo platelet activation and patients with atherosclerotic vascular disease exhibit higher levels of MPA. Clopidogrel has been shown to reduce MPA formation in these patients to a greater extent than aspirin. However, response to clopidogrel and aspirin shows a wide variability, and patients with high on-treatment residual platelet reactivity are at an increased risk for adverse events after coronary stenting. We therefore investigated the association of MPA with on-treatment residual agonists'-inducible platelet aggregation in 125 patients on dual antiplatelet therapy after peripheral, coronary or carotid artery stenting.
  
  
  METHODS
  MPA were characterized by co-expression of monocyte marker CD14 and platelet-specific markers (CD42b and CD62P) by whole blood flow cytometry. Platelet reactivity was determined by light transmission aggregometry, the VerifyNow P2Y12 and aspirin assays, and the vasodilator-stimulated phosphoprotein phosphorylation assay. Cut-off values for residual platelet reactivity were defined according to quartiles of each assay.
  
  
  RESULTS
  The extent of MPA formation showed no significant differences between patients without and with residual ADP-inducible platelet reactivity, and between individuals without and with residual arachidonic acid (AA)-inducible platelet reactivity. Even patients with combined on-treatment residual ADP- and AA-inducible platelet reactivity did not exhibit significantly higher levels of MPA than patients without any on-treatment residual platelet reactivity.
  
  
  CONCLUSIONS
  High on-treatment residual agonists'-inducible platelet reactivity results in less than a 25% increase in circulating MPA, suggesting that MPA formation is largely dependent on other factors.
authors.affiliation: Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Georgiana-Aura
authors.initials: GA
authors.lastname: Giurgea
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000244:Adenosine Diphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000800:Angioplasty, Balloon / Q000295:instrumentation; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation; D016718:Arachidonic Acid; D001241:Aspirin / Q000627:therapeutic use*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D019007:P-Selectin / Q000097:blood; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D018950:Lipopolysaccharide Receptors; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D000098662:Vasodilator-Stimulated Phosphoprotein; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin