High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke

Results from the Trinity Antiplatelet Responsiveness (TRAP) study

William Tobin, J. A. Kinsella, T. Coughlan, D. R. Collins, D. O'Neill, R. P. Murphy, B. Egan, S. Tierney, T. M. Feeley, D. J H Mccabe

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background and purpose: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. Methods: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. Results: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. Conclusions: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.

Original languageEnglish (US)
Pages (from-to)344-352
Number of pages9
JournalEuropean Journal of Neurology
Volume20
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

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Platelet Aggregation Inhibitors
Transient Ischemic Attack
clopidogrel
Blood Platelets
Stroke
Aspirin
Cerebrovascular Disorders
Collagen
Therapeutics
Platelet Activation
Adenosine Diphosphate
Epinephrine
Platelet Function Tests
Blood Vessels
Flow Cytometry
Neutrophils
Leukocytes
Prospective Studies

Keywords

  • Aspirin
  • Clopidogrel
  • Flow cytometry
  • High on-treatment platelet reactivity
  • Platelet function analyser-100
  • Stroke
  • Transient ischaemic attack

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke : Results from the Trinity Antiplatelet Responsiveness (TRAP) study. / Tobin, William; Kinsella, J. A.; Coughlan, T.; Collins, D. R.; O'Neill, D.; Murphy, R. P.; Egan, B.; Tierney, S.; Feeley, T. M.; Mccabe, D. J H.

In: European Journal of Neurology, Vol. 20, No. 2, 02.2013, p. 344-352.

Research output: Contribution to journalArticle

Tobin, William ; Kinsella, J. A. ; Coughlan, T. ; Collins, D. R. ; O'Neill, D. ; Murphy, R. P. ; Egan, B. ; Tierney, S. ; Feeley, T. M. ; Mccabe, D. J H. / High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke : Results from the Trinity Antiplatelet Responsiveness (TRAP) study. In: European Journal of Neurology. 2013 ; Vol. 20, No. 2. pp. 344-352.
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abstract = "Background and purpose: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. Methods: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. Results: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24{\%} at 14 days and 18{\%} at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41{\%} at 14 days, and 35{\%} at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. Conclusions: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.",
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author = "William Tobin and Kinsella, {J. A.} and T. Coughlan and Collins, {D. R.} and D. O'Neill and Murphy, {R. P.} and B. Egan and S. Tierney and Feeley, {T. M.} and Mccabe, {D. J H}",
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T1 - High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke

T2 - Results from the Trinity Antiplatelet Responsiveness (TRAP) study

AU - Tobin, William

AU - Kinsella, J. A.

AU - Coughlan, T.

AU - Collins, D. R.

AU - O'Neill, D.

AU - Murphy, R. P.

AU - Egan, B.

AU - Tierney, S.

AU - Feeley, T. M.

AU - Mccabe, D. J H

PY - 2013/2

Y1 - 2013/2

N2 - Background and purpose: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. Methods: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. Results: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. Conclusions: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.

AB - Background and purpose: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. Methods: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. Results: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. Conclusions: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.

KW - Aspirin

KW - Clopidogrel

KW - Flow cytometry

KW - High on-treatment platelet reactivity

KW - Platelet function analyser-100

KW - Stroke

KW - Transient ischaemic attack

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