Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients

J Thromb Haemost. 2007 Sep;5(9):1839-47. doi: 10.1111/j.1538-7836.2007.02656.x.


Background: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (RPR) in coronary artery disease (CAD) patients.

Objectives and methods: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5'-diphosphate (ADP) (C/ADP CT) cartridge and the VerifyNow P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 micromol L(-1) ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients.

Results: Cut-off values for identifying RPR were: > or = 54% and > or = 66% for LTA induced by 2 and 10 micromol L(-1) ADP respectively, and > or = 264 P2Y12 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was > or = 68 s. RPR was detected in 25.1% of patients by 2 mumol L(-1) ADP-induced LTA (ADP-LTA), in 23.2% by 10 micromol L(-1) ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 micromol L(-1) ADP. The correlation was similar but the agreement was better between VerifyNow and 10 micromol L(-1) ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays.

Conclusions: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.

MeSH terms

  • Aged
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / pathology
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine