Abstract 5305: Intracoronary Upregulation of Platelet P-selectin and Platelet-monocyte Aggregation Correlate With Coronary Lesion Stenosis Severity Despite Aspirin and Clopidogrel Use

Abstract

Background: In vitro studies suggest that platelets are activated by shear stress as they travel through areas of significant coronary stenosis. However, it is unknown whether coronary stenoses cause platelet activation in the presence of dual anti-platelet therapy with aspirin and clopidogrel. We hypothesized that platelet P-selectin, a key regulator of platelet-leukocyte interactions and inflammation, is upregulated as platelets cross coronary plaques despite dual anti-platelet therapy, and this upregulation is directly associated with stenosis severity. Methods: Prior to PCI, blood was collected in sequence from the coronary sinus (CS, in left coronary target lesions), coronary artery distal (DA) and proximal (PA) to target lesion, and CS a second time immediately after intracoronary sampling. Quantitative coronary angiography was used to measure target lesion percentage area stenosis. Percentage platelet P-selectin (CD62P) expression, GPIIb/IIIa conformational change (PAC-1), and platelet-monocyte aggregate formation were quantified by flow cytometry. Results: In total, 15 consecutive patients pre-treated with dual anti-platelet therapy undergoing elective percutaneous coronary intervention (PCI) to a single target lesion were recruited. Mean age was 67.5y, and 88% were male. Mean percentage lesion area stenosis was 80.8±8.2%. Percentage area stenosis correlated with trans-lesion gradients (DA-PA) for CD62P (r=0.62, p=0.01) and platelet-monocyte aggregation (r=0.76, p<0.01), but not for PAC-1 (r=0.03, p=0.90). CS samples were significantly more activated than PA for CD62P (p=0.03) but CS samples and trans-cardiac gradients (CS-PA) did not correlate with lesion stenosis. There were no significant differences between first and second CS samples, indicating no artificial activation caused by sampling. Conclusions: We provide evidence of a direct relationship between coronary stenosis severity and intracoronary platelet P-selectin expression and platelet-monocyte aggregation despite dual anti-platelet therapy. Upregulation of P-selectin by shear stress and/or other mechanical factors under conditions where IIb/IIIa is not, appears to be resistant to current conventional anti-platelet therapy.