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J Am Coll Cardiol, 2005; 46:1820-1826, doi:10.1016/j.jacc.2005.07.041 (Published online 19 October 2005).
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: PLATELETS AND STENT THROMBOSIS

Platelet Reactivity in Patients and Recurrent Events Post-Stenting

Results of the PREPARE POST-STENTING Study

Paul A. Gurbel, MD*,*, Kevin P. Bliden, BS*, Kirk Guyer, BS{dagger}, Peter W. Cho, MD{ddagger}, Kazi A. Zaman, MD*, Rolf P. Kreutz, MD*, Ashwani K. Bassi, MD* and Udaya S. Tantry, PhD*

* Sinai Center for Thrombosis Research, Baltimore, Maryland
{dagger} Indiana University, Department of Chemistry, South Bend, Indiana
{ddagger} Department of Surgery, Sinai Hospital, Baltimore, Maryland

Manuscript received April 14, 2005; revised manuscript received July 8, 2005, accepted July 11, 2005.

* Reprint requests and correspondence: Dr. Paul A. Gurbel, Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 West Belvedere Avenue, Baltimore, Maryland 21215. (Email: pgurbel{at}lifebridgehealth.org).

OBJECTIVES: We investigated the relation of high ex vivo platelet reactivity, rapid fibrin generation, and high thrombin-induced clot strength to postdischarge ischemic events in patients undergoing percutaneous coronary intervention (PCI).

BACKGROUND: High platelet reactivity and rapid fibrin generation may affect the incidence of ischemic events after PCI. However, limited data is available to link these ex vivo markers to the occurrence of events.

METHODS: We measured platelet reactivity to adenosine diphosphate (ADP) by light transmittance aggregometry (LTA) in patients undergoing PCI (n = 192). Clot strength, a measure of thrombin-induced fibrin and platelet interactions, and the time to initial fibrin generation, a marker of thrombin activity, were measured by thrombelastography. The relation of these measurements to ischemic event occurrence was prospectively examined over six months.

RESULTS: A total of 100% and 84% of patients were on aspirin and clopidogrel therapy, respectively, at the time of the initial event. Posttreatment ADP-induced aggregation by LTA (63 ± 12% vs. 56 ± 15%, p = 0.02) and clot strength (MA) were higher (74 ± 5 mm vs. 65 ± 4 mm, p < 0.001) and time to initial fibrin generation was shorter (4.3 ± 1.3 min vs. 5.9 ± 1.5 min, p < 0.001) in patients with events (n = 38). The event rates in the highest quartiles of LTA and MA were 32% and 58%, respectively.

CONCLUSIONS: High platelet reactivity and clot strength, and rapid fibrin formation are novel risk factors for ischemic events after PCI. Clot strength is more predictive than ADP-induced platelet aggregation and may explain the occurrence of events despite treatment with cyclooxygenase-1 and P2Y12 inhibitors.

Abbreviations and Acronyms
  ADP = adenosine diphosphate
  GP = glycoprotein
  LTA = light transmittance aggregometry
  MA = clot strength
  PCI = percutaneous coronary intervention
  PPP = platelet-poor plasma
  PRP = platelet-rich plasma
  R = reaction time
  ROC = receiver operator curve
  TEG = thrombelastograph
  TVR = target vessel revascularization




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