Lack of uniform platelet activation in patients after ischemic stroke and choice of antiplatelet therapy

Victor L. Serebruany, Alex I. Malinin, Benjamin R. Oshrine, David C. Sane, Aviv Takserman, Dan Atar, Charles H. Hennekens

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Platelets play an important role in the natural history of ischemic stroke, and are known to be activated in the acute phase. Although aspirin reduces risks of myocardial infarction, stroke and cardiovascular death, the extent of platelet action and the effect of aspirin on platelet function in patients recovering from stroke remain unclear. Methods: We studied 120 individuals divided into three equal groups: aspirin-free patients after ischemic stroke, post-stroke patients receiving aspirin (81-650 mg/daily), and aspirin-free subjects with multiple risk factors for vascular disease. Conventional platelet aggregation induced by 5 μM ADP and 5 μM epinephrine, cartridge-based analyzers (Ultegra®, and PFA-100™) readings, and expression of CD31, CD41a, CD42b, GPIIb/IIIa activity, CD51/CD61, CD62p, CD63, CD107a, CD154, CD165, formation of platelet-monocyte aggregates, intact (SPAN12), and cleaved (WEDE15) PAR-1 thrombin receptors by flow cytometry were analyzed. Results: There were no differences between aspirin-free post-stroke patients and aspirin-free controls. Although aggregation was slightly higher, 12 out of the 14 receptor analyses, were surprisingly lower in the post-stroke cohort. Aspirin-treated patients exhibited highly significant inhibition of epinephrine-induced aggregation (p=0.0001), prolongation of the closure time (p=0.03), and reduction of the aspirin reactive units (p=0.02) measured by the Ultegra® device. In addition, surface platelet expression of thrombospondin (p=0.001), GPIIb/IIIa activity (p=0.04), P-selectin (p=0.03), CD40-ligand (p=0.04), CD165 (p=0.02), the formation of the platelet-monocyte aggregates (p=0.01), and intact epitope of PAR-1 thrombin receptor (p=0.03) were significantly lower in the aspirin-treated group. Conclusions: Platelets are not activated in aspirin-free patients after ischemic stroke. Platelet function is significantly inhibited in those treated with aspirin when compared with healthy subjects with risk factors for vascular disease. Bleeding complications and hemorrhagic transformations after aggressive antiplatelet regimens could be related to the decreased or normal baseline platelet characteristics in such patients. Further analysis of platelet heterogeneity and its clinical significance remains to be determined in randomized trials.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalThrombosis Research
Volume113
Issue number3-4
DOIs
StatePublished - 2004

Keywords

  • adenosine diphosphate
  • ADP
  • ARU
  • ASA
  • Aspirin
  • aspirin
  • aspirin response unit
  • CD
  • cluster of differentiations
  • GP
  • LAMP
  • lyzosome associated membrane protein
  • non-steroids anti-inflammatory drugs
  • NSAIDS
  • PECAM
  • platelet glycoprotein
  • Platelets
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

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