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.

Clinical Pharmacology & Therapeutics (2003) 73, 232–241; doi: 10.1067/mcp.2003.13