title: 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.
abstract: OBJECTIVE
  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-mumol/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-mug/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.
authors: Department of Cardiology, Methodist DeBakey Heart and Vascular Center and Methodist Hospital Research Institute, Houston, Texas, USA.
authors: Sasidhar
authors: S
authors: Guthikonda
authors: Carlos L
authors: CL
authors: Alviar
authors: Muthiah
authors: M
authors: Vaduganathan
authors: Mehmet
authors: M
authors: Arikan
authors: Armando
authors: A
authors: Tellez
authors: Timothy
authors: T
authors: DeLao
authors: Juan F
authors: JF
authors: Granada
authors: Jing-Fei
authors: JF
authors: Dong
authors: Neal S
authors: NS
authors: Kleiman
authors: Eli I
authors: EI
authors: Lev
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D048429:Cell Size; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010976:Platelet Count; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin