Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis

Justin A. Kinsella, William Tobin, Sean Tierney, Timothy M. Feeley, Bridget Egan, Tara Coughlan, D. Ronan Collins, Desmond O'Neill, Joseph A. Harbison, Colin P. Doherty, Prakash Madhavan, Dermot J. Moore, Sean M. O'Neill, Mary Paula Colgan, Maher Saqqur, Raymond P. Murphy, Niamh Moran, George Hamilton, Dominick J.H. McCabe

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. Methods Consecutive eligible patients with ≥ 50% asymptomatic or recently symptomatic carotid stenosis (≤ 4 weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥ 3 months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES + ve or MES − ve. Results 31 patients with ≥ 50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p = 0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p = 0.017), including those on aspirin monotherapy (p = 0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES + ve or MES − ve patients. Discussion Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalJournal of the Neurological Sciences
Volume376
DOIs
StatePublished - May 15 2017
Externally publishedYes

Fingerprint

Carotid Stenosis
Blood Platelets
Therapeutics
Aspirin
Collagen
Epinephrine
Doppler Ultrasonography
Acute-Phase Reaction
Middle Cerebral Artery
Citric Acid
Adenosine Diphosphate
Longitudinal Studies

Keywords

  • Carotid stenosis
  • Cerebral microembolic signals
  • Ischaemic stroke
  • On-treatment platelet reactivity
  • TIA

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis. / Kinsella, Justin A.; Tobin, William; Tierney, Sean; Feeley, Timothy M.; Egan, Bridget; Coughlan, Tara; Ronan Collins, D.; O'Neill, Desmond; Harbison, Joseph A.; Doherty, Colin P.; Madhavan, Prakash; Moore, Dermot J.; O'Neill, Sean M.; Colgan, Mary Paula; Saqqur, Maher; Murphy, Raymond P.; Moran, Niamh; Hamilton, George; McCabe, Dominick J.H.

In: Journal of the Neurological Sciences, Vol. 376, 15.05.2017, p. 133-139.

Research output: Contribution to journalArticle

Kinsella, JA, Tobin, W, Tierney, S, Feeley, TM, Egan, B, Coughlan, T, Ronan Collins, D, O'Neill, D, Harbison, JA, Doherty, CP, Madhavan, P, Moore, DJ, O'Neill, SM, Colgan, MP, Saqqur, M, Murphy, RP, Moran, N, Hamilton, G & McCabe, DJH 2017, 'Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis', Journal of the Neurological Sciences, vol. 376, pp. 133-139. https://doi.org/10.1016/j.jns.2017.03.015
Kinsella, Justin A. ; Tobin, William ; Tierney, Sean ; Feeley, Timothy M. ; Egan, Bridget ; Coughlan, Tara ; Ronan Collins, D. ; O'Neill, Desmond ; Harbison, Joseph A. ; Doherty, Colin P. ; Madhavan, Prakash ; Moore, Dermot J. ; O'Neill, Sean M. ; Colgan, Mary Paula ; Saqqur, Maher ; Murphy, Raymond P. ; Moran, Niamh ; Hamilton, George ; McCabe, Dominick J.H. / Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis. In: Journal of the Neurological Sciences. 2017 ; Vol. 376. pp. 133-139.
@article{a7b9baeef912413696b10c20e4547292,
title = "Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis",
abstract = "Introduction The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. Methods Consecutive eligible patients with ≥ 50{\%} asymptomatic or recently symptomatic carotid stenosis (≤ 4 weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥ 3 months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100{\circledR} to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES + ve or MES − ve. Results 31 patients with ≥ 50{\%} asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10{\%} vs. 50{\%}; p = 0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63{\%} vs. 34{\%}; p = 0.017), including those on aspirin monotherapy (p = 0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES + ve or MES − ve patients. Discussion Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.",
keywords = "Carotid stenosis, Cerebral microembolic signals, Ischaemic stroke, On-treatment platelet reactivity, TIA",
author = "Kinsella, {Justin A.} and William Tobin and Sean Tierney and Feeley, {Timothy M.} and Bridget Egan and Tara Coughlan and {Ronan Collins}, D. and Desmond O'Neill and Harbison, {Joseph A.} and Doherty, {Colin P.} and Prakash Madhavan and Moore, {Dermot J.} and O'Neill, {Sean M.} and Colgan, {Mary Paula} and Maher Saqqur and Murphy, {Raymond P.} and Niamh Moran and George Hamilton and McCabe, {Dominick J.H.}",
year = "2017",
month = "5",
day = "15",
doi = "10.1016/j.jns.2017.03.015",
language = "English (US)",
volume = "376",
pages = "133--139",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
publisher = "Elsevier",

}

TY - JOUR

T1 - Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis

AU - Kinsella, Justin A.

AU - Tobin, William

AU - Tierney, Sean

AU - Feeley, Timothy M.

AU - Egan, Bridget

AU - Coughlan, Tara

AU - Ronan Collins, D.

AU - O'Neill, Desmond

AU - Harbison, Joseph A.

AU - Doherty, Colin P.

AU - Madhavan, Prakash

AU - Moore, Dermot J.

AU - O'Neill, Sean M.

AU - Colgan, Mary Paula

AU - Saqqur, Maher

AU - Murphy, Raymond P.

AU - Moran, Niamh

AU - Hamilton, George

AU - McCabe, Dominick J.H.

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Introduction The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. Methods Consecutive eligible patients with ≥ 50% asymptomatic or recently symptomatic carotid stenosis (≤ 4 weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥ 3 months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES + ve or MES − ve. Results 31 patients with ≥ 50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p = 0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p = 0.017), including those on aspirin monotherapy (p = 0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES + ve or MES − ve patients. Discussion Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

AB - Introduction The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. Methods Consecutive eligible patients with ≥ 50% asymptomatic or recently symptomatic carotid stenosis (≤ 4 weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥ 3 months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES + ve or MES − ve. Results 31 patients with ≥ 50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p = 0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p = 0.017), including those on aspirin monotherapy (p = 0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES + ve or MES − ve patients. Discussion Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

KW - Carotid stenosis

KW - Cerebral microembolic signals

KW - Ischaemic stroke

KW - On-treatment platelet reactivity

KW - TIA

UR - http://www.scopus.com/inward/record.url?scp=85015682706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015682706&partnerID=8YFLogxK

U2 - 10.1016/j.jns.2017.03.015

DO - 10.1016/j.jns.2017.03.015

M3 - Article

C2 - 28431600

AN - SCOPUS:85015682706

VL - 376

SP - 133

EP - 139

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

ER -