Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis

J Neurol. 2020 Jan;267(1):168-184. doi: 10.1007/s00415-019-09550-3. Epub 2019 Oct 12.

Abstract

Background: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy.

Methods: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve.

Results: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup.

Discussion: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Keywords: Carotid stenosis; High on-treatment platelet reactivity; Micro-embolic signals; Platelet function; Transcranial Doppler ultrasound.

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Blood Platelets* / drug effects
  • Blood Platelets* / physiology
  • Brain Ischemia / drug therapy
  • Carotid Stenosis / diagnostic imaging
  • Carotid Stenosis / drug therapy*
  • Female
  • Humans
  • Intracranial Embolism / diagnostic imaging
  • Intracranial Embolism / drug therapy*
  • Male
  • Middle Aged
  • Middle Cerebral Artery / diagnostic imaging
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Prospective Studies
  • Stroke / drug therapy
  • Ultrasonography, Doppler, Transcranial

Substances

  • Platelet Aggregation Inhibitors
  • Aspirin