The Significance of Vasodilator-Stimulated Phosphoprotein for Risk Stratification of Stent Thrombosis

Thromb Haemost. 2007 Dec;98(6):1329-34.

Abstract

Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis (ST). This prospective observational study assessed the capability of two platelet function assays, e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet aggregation for definition of the individual risk to develop ST. Ninety-nine patients with an elevated high risk to develop ST were enrolled. All patients received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel during an observation period of six months. Flow cytometry of VASP phosphorylation and densitometrically-determined measurement of ADP-induced platelet aggregation was performed 72-96 hours after stent implantation. These data were related to angiographically confirmed ST. Nine patients suffered from angiographically confirmed ST (9.1%). The meanVASP-platelet reactivity indices (VASP-PRI) and values for ADP-induced platelet aggregation in the ST group were significantly higher (60.8 +/- 13.0 and 60.9 +/- 13.1, respectively) compared to patients without ST (41.3 +/- 14.0 and 50.8 +/- 14.4, P < 0.001 vs. 0.048, respectively). There was a fair correlation between both methods using non-linear regression analysis (r = 0.332). In a multivariate analysis, VASP was the only independent predictor of ST and was superior to previously identified angiographic parameters. Receiver- operator characteristic (ROC) curve analysis revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of ST. In conclusion, determination of VASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased risk.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adenosine Diphosphate
  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects*
  • Angioplasty, Balloon, Coronary / instrumentation
  • Aspirin / therapeutic use
  • Cell Adhesion Molecules / blood*
  • Clopidogrel
  • Coronary Angiography
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Microfilament Proteins / blood*
  • Middle Aged
  • Phosphoproteins / blood*
  • Phosphorylation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Aggregation*
  • Platelet Function Tests* / methods
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Reproducibility of Results
  • Research Design
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Stents*
  • Thrombosis / blood
  • Thrombosis / diagnosis*
  • Thrombosis / diagnostic imaging
  • Thrombosis / etiology
  • Thrombosis / prevention & control
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • vasodilator-stimulated phosphoprotein
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine
  • Aspirin