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J Am Coll Cardiol, 2005; 46:1705-1709, doi:10.1016/j.jacc.2005.05.090 (Published online 7 October 2005).
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: ASPIRIN RESISTANCE

Overestimation of Platelet Aspirin Resistance Detection by Thrombelastograph Platelet Mapping and Validation by Conventional Aggregometry Using Arachidonic Acid Stimulation

Udaya S. Tantry, PhD, Kevin P. Bliden, BS and Paul A. Gurbel, MD, FACC*

Sinai Center for Thrombosis Research, Baltimore, Maryland

Manuscript received March 21, 2005; revised manuscript received May 13, 2005, accepted May 22, 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: This study sought to determine the prevalence of platelet aspirin resistance using methods that directly indicate the degree of platelet cyclooxygenase inhibition.

BACKGROUND: Aspirin resistance in platelets may be overestimated by nonspecific laboratory measurements that do not isolate cyclooxygenase activity.

METHODS: Arachidonic acid (AA)-induced light-transmittance platelet aggregation (LTA) and thrombelastography (TEG) platelet mapping were performed on the blood of healthy subjects (n = 6) before and 24 h after receiving 325 mg aspirin, and on 223 patients reporting compliance with long-term daily aspirin treatment (n = 203 undergoing percutaneous intervention [PCI] and n = 20 with a history of stent thrombosis). Aspirin resistance was defined as >20% aggregation by LTA or >50% aggregation by TEG.

RESULTS: In healthy subjects, AA-induced aggregation by LTA was 82 ± 10% before and 2 ± 1% at 24 h after aspirin (p < 0.001), and aggregation by TEG was 86 ± 14% before and 5 ± 7% at 24 h after aspirin (p < 0.001). In compliant patients, AA-induced aggregation by LTA was 3 ± 2% before PCI and 3 ± 2% after PCI (p = NS), and aggregation by TEG was 5 ± 9% before PCI and 6 ± 14% after PCI (p = NS). Seven PCI patients were noncompliant, and all were aspirin sensitive after in-hospital aspirin treatment. Among 223 patients, only one patient (~0.4%) was resistant to aspirin treatment.

CONCLUSIONS: Platelet aspirin resistance assessed by methods that directly indicate inhibition of cyclooxygenase is rare in compliant patients with coronary artery disease.

Abbreviations and Acronyms
  AA = arachidonic acid
  ADP = adenosine diphosphate
  COX-1 = cyclooxygenase-1
  GP = glycoprotein
  LTA = light-transmittance aggregometry
  MAAA = arachidonic acid-induced clot strength (measurement of aspirin effect)
  MAfibrin = activator-induced clot strength (measurement of fibrin contribution)
  MAthrombin = thrombin-induced clot strength (maximum clot strength)
  PCI = percutaneous coronary intervention
  PPP = platelet-poor plasma
  PRP = platelet-rich plasma
  SAT = stent thrombosis
  TEG = thrombelastography




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