Role of Reticulated Platelets and Platelet Size Heterogeneity on Platelet Activity After Dual Antiplatelet Therapy With Aspirin and Clopidogrel in Patients With Stable Coronary Artery Disease

Sasidhar Guthikonda, Carlos L. Alviar, Muthiah Vaduganathan, Mehmet Arikan, Armando Tellez, Timothy DeLao, Juan F. Granada, Jing Fei Dong, Neal Kleiman, Eli I. Lev

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

Objectives: The aim of this study was to evaluate the relationship between reticulated platelets (RPs), platelet size, and platelet function in patients with stable coronary artery disease (CAD) taking aspirin and clopidogrel. Background: Reticulated platelets are young platelets that are larger and possibly more active than non-RPs. Methods: Flow cytometry was used to measure RPs after staining with thiazole orange and to define the upper 20% and lower 20% of platelets by size. Platelet aggregation was measured with light transmission aggregometry (LTA); platelet activation was assessed by measuring activated platelet surface expression of P-selectin and glycoprotein (GP) IIb/IIIa. Results: Ninety patients were recruited and stratified into tertiles of %RPs. Patients in the upper tertile displayed greater platelet aggregation to 5-μmol/l adenosine diphosphate (ADP) (50.7 ± 16.4% vs. 34.2 ± 17.3%, p < 0.001), 1.5-mmol/l arachidonic acid (AA) (27.3 ± 16.9% vs. 11.7 ± 9.3%, p < 0.001), and 1-μg/ml collagen (18 ± 11.6% vs. 12.1 ± 8.7%, p < 0.05) and greater expression of GP IIb/IIIa (4.7 ± 1.8% vs. 3.1 ± 2.2%, p < 0.001). Frequency of low response to aspirin (AA LTA >20%) was higher in the upper tertile (53% vs. 17%, p < 0.001) compared with the lower tertile; low response to clopidogrel (ADP LTA >50%) was also elevated in the upper tertile (50% vs. 13%, p = 0.003). The larger platelet gate had a higher % of RPs compared with the smaller gate (15.4 ± 16.7% vs. 1.7 ± 2.3%, p < 0.001) and greater GP IIb/IIIa (5.7 ± 3.1 vs. 2.1 ± 1.2, p < 0.001) and P-selectin expression (7.8 ± 4.9 vs. 4.6 ± 2.7, p < 0.001). Conclusions: The proportion of circulating RPs strongly correlates with response to antiplatelet therapy in patients with stable CAD. Large platelets exhibit increased reactivity despite dual antiplatelet therapy, compared with smaller platelets.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalJournal of the American College of Cardiology
Volume52
Issue number9
DOIs
StatePublished - Aug 26 2008

Keywords

  • aspirin
  • coronary artery disease
  • platelets

ASJC Scopus subject areas

  • Nursing(all)

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