The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists'-inducible platelet reactivity

Atherosclerosis. 2009 Dec;207(2):608-13. doi: 10.1016/j.atherosclerosis.2009.05.037. Epub 2009 Jun 18.

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.

Conclusion: 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.

MeSH terms

  • Adenosine Diphosphate
  • Adult
  • Aged
  • Aged, 80 and over
  • Angioplasty, Balloon* / instrumentation
  • Angioplasty, Balloon, Coronary* / instrumentation
  • Arachidonic Acid
  • Aspirin / therapeutic use*
  • Case-Control Studies
  • Cell Adhesion Molecules / blood
  • Clopidogrel
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • Humans
  • Lipopolysaccharide Receptors / blood
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / immunology
  • P-Selectin / blood
  • Phosphoproteins / blood
  • Phosphorylation
  • Platelet Adhesiveness / drug effects*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIb-IX Complex / metabolism
  • Stents
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Cell Adhesion Molecules
  • Lipopolysaccharide Receptors
  • Microfilament Proteins
  • P-Selectin
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIb-IX Complex
  • vasodilator-stimulated phosphoprotein
  • Arachidonic Acid
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine
  • Aspirin