Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease

Clin Pharmacol Ther. 2003 Mar;73(3):232-41. doi: 10.1067/mcp.2003.13.


Formation of platelet-leukocyte aggregates via the CD62 ligand represents an important mechanism by which leukocytes contribute to thrombotic events. In a cross-sectional study, we investigated platelet-leukocyte aggregate formation and markers indicative for platelet, leukocyte, and endothelial activation (CD62, activated fibrinogin receptor glycoprotein IIb/IIIA [PAC-1], CD11b/CD18 [MAC-1], and soluble intercellular adhesion molecule 1) in 44 patients with atherosclerotic vascular disease and peripheral occlusions receiving clopidogrel (n = 12), aspirin (n = 17), their combination (n = 8), or no treatment (n = 7), as well as in a group of healthy subjects (n = 9). Whole-blood flow cytometry was performed before (baseline) and after stimulation with thrombin receptor-activating peptide or adenosine diphosphate. Both at baseline and after stimulation, untreated patients and those receiving aspirin monotherapy exhibited significantly higher levels of platelet CD62 expression (baseline CD62: untreated, 22% [median]; with aspirin, 16%) and had higher rates of platelet-leukocyte aggregate formation (monocyte-platelet-leukocyte aggregates at baseline: untreated, 27%; with aspirin, 16%) when compared with patients receiving clopidogrel alone (baseline CD62: 10% [P <.05]; monocyte-platelet-leukocyte aggregates: 13% [P <.05]) or combined with aspirin (baseline CD62: 5% [P <.05]; monocyte-platelet-leukocyte aggregates: 7% [P <.05]). Up-regulation of MAC-1 on monocytes after stimulation with thrombin receptor-activating peptide and adenosine diphosphate was significantly lower in patients treated with clopidogrel and aspirin. Plasma levels of soluble intercellular adhesion molecule 1 were significantly lower in the group of healthy subjects (median, 186 ng/mL) when compared with those in untreated patients (median, 352 ng/mL) (P <.05), whereas intercellular adhesion molecule 1 levels in treated patients were similar for any antiplatelet regimen (aspirin, 262 ng/mL; clopidogrel, 274 ng/mL; combination therapy, 273 ng/mL) but significantly lower than those in untreated patients. This is the first report showing that platelet-leukocyte aggregate formation is enhanced in atherosclerotic vascular disease but was found to be reduced in patients receiving clopidogrel.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Blood Platelets / metabolism*
  • Case-Control Studies
  • Clopidogrel
  • Coronary Artery Disease / drug therapy
  • Cross-Sectional Studies
  • Drug Therapy, Combination
  • Dual Specificity Phosphatase 2
  • Female
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocytes / metabolism*
  • Male
  • Middle Aged
  • P-Selectin / metabolism*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Protein Phosphatase 2
  • Protein Tyrosine Phosphatases / metabolism
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology*
  • Ticlopidine / therapeutic use


  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Intercellular Adhesion Molecule-1
  • Clopidogrel
  • Protein Phosphatase 2
  • DUSP2 protein, human
  • Dual Specificity Phosphatase 2
  • Protein Tyrosine Phosphatases
  • Ticlopidine
  • Aspirin