Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.

Data on the agreement between aggregometry and platelet activation by flow cytometry regarding the measurement of on-treatment platelet reactivity to arachidonic acid (AA) and adenosine diphosphate (ADP) are scarce. We therefore sought to compare three platelet aggregation tests with flow cytometry...

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Main Authors: Thomas Gremmel, Renate Koppensteiner, Simon Panzer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4461164?pdf=render
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author Thomas Gremmel
Renate Koppensteiner
Simon Panzer
author_facet Thomas Gremmel
Renate Koppensteiner
Simon Panzer
author_sort Thomas Gremmel
collection DOAJ
description Data on the agreement between aggregometry and platelet activation by flow cytometry regarding the measurement of on-treatment platelet reactivity to arachidonic acid (AA) and adenosine diphosphate (ADP) are scarce. We therefore sought to compare three platelet aggregation tests with flow cytometry for the assessment of the response to antiplatelet therapy. Platelet aggregation in response to AA and ADP was determined by light transmission aggregometry (LTA), the VerifyNow assays, and multiple electrode aggregometry (MEA) in 316 patients receiving aspirin and clopidogrel therapy after angioplasty with stent implantation. AA- and ADP-induced P-selectin expression and activated glycoprotein (GP) IIb/IIIa were determined by flow cytometry. LTA, the VerifyNow P2Y12 assay and MEA in response to ADP correlated significantly (all p<0.001), and the best correlation was observed between LTA and the VerifyNow P2Y12 assay (r = 0.63). ADP-induced platelet reactivity by all aggregation tests correlated significantly with ADP-induced P-selectin expression and activated GPIIb/IIIa (all p<0.001). The best correlation was seen between the VerifyNow P2Y12 assay and activated GPIIb/IIIa (r = 0.68). The platelet surface expressions of P-selectin and activated GPIIb/IIIa in response to ADP were significantly higher in patients with high on-treatment residual platelet reactivity (HRPR) to ADP by all test systems (all p<0.001). A rather poor correlation was observed between AA-induced platelet reactivity by LTA and the VerifyNow aspirin assay (r = 0.15, p = 0.007), while both methods did not correlate with MEA. AA-induced platelet reactivity by all aggregation tests correlated significantly, but rather poorly with AA-induced P-selectin expression (all p<0.05), while only AA-induced platelet reactivity by LTA correlated significantly with AA-induced activated GPIIb/IIIa (r = 0.21, p<0.001). The platelet surface expression of P-selectin in response to AA was significantly higher in patients with HRPR by LTA AA and MEA AA (both p<0.02). In contrast, P-selectin expression in response to AA was similar in patients without and with HRPR by the VerifyNow aspirin assay (p = 0.5), and platelet surface activated GPIIb/IIIa in response to AA did not differ significantly between patients without and with HRPR to AA by all test systems (all p>0.1). In conclusion, ADP-induced platelet reactivity by aggregometry translates partly into flow cytometry. In contrast, AA-induced platelet reactivity correlates poorly between different platelet aggregation tests, and between aggregometry and flow cytometry. Overall, both approaches capture different aspects of platelet function and are therefore not interchangeable in the assessment of agonists´-induced platelet reactivity. Clinical outcome data are needed to determine which test systems and settings are associated with different in vivo consequences.
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spelling doaj.art-8445d9ab5ecb41b4a234a8fe5be201482022-12-22T01:34:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012966610.1371/journal.pone.0129666Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.Thomas GremmelRenate KoppensteinerSimon PanzerData on the agreement between aggregometry and platelet activation by flow cytometry regarding the measurement of on-treatment platelet reactivity to arachidonic acid (AA) and adenosine diphosphate (ADP) are scarce. We therefore sought to compare three platelet aggregation tests with flow cytometry for the assessment of the response to antiplatelet therapy. Platelet aggregation in response to AA and ADP was determined by light transmission aggregometry (LTA), the VerifyNow assays, and multiple electrode aggregometry (MEA) in 316 patients receiving aspirin and clopidogrel therapy after angioplasty with stent implantation. AA- and ADP-induced P-selectin expression and activated glycoprotein (GP) IIb/IIIa were determined by flow cytometry. LTA, the VerifyNow P2Y12 assay and MEA in response to ADP correlated significantly (all p<0.001), and the best correlation was observed between LTA and the VerifyNow P2Y12 assay (r = 0.63). ADP-induced platelet reactivity by all aggregation tests correlated significantly with ADP-induced P-selectin expression and activated GPIIb/IIIa (all p<0.001). The best correlation was seen between the VerifyNow P2Y12 assay and activated GPIIb/IIIa (r = 0.68). The platelet surface expressions of P-selectin and activated GPIIb/IIIa in response to ADP were significantly higher in patients with high on-treatment residual platelet reactivity (HRPR) to ADP by all test systems (all p<0.001). A rather poor correlation was observed between AA-induced platelet reactivity by LTA and the VerifyNow aspirin assay (r = 0.15, p = 0.007), while both methods did not correlate with MEA. AA-induced platelet reactivity by all aggregation tests correlated significantly, but rather poorly with AA-induced P-selectin expression (all p<0.05), while only AA-induced platelet reactivity by LTA correlated significantly with AA-induced activated GPIIb/IIIa (r = 0.21, p<0.001). The platelet surface expression of P-selectin in response to AA was significantly higher in patients with HRPR by LTA AA and MEA AA (both p<0.02). In contrast, P-selectin expression in response to AA was similar in patients without and with HRPR by the VerifyNow aspirin assay (p = 0.5), and platelet surface activated GPIIb/IIIa in response to AA did not differ significantly between patients without and with HRPR to AA by all test systems (all p>0.1). In conclusion, ADP-induced platelet reactivity by aggregometry translates partly into flow cytometry. In contrast, AA-induced platelet reactivity correlates poorly between different platelet aggregation tests, and between aggregometry and flow cytometry. Overall, both approaches capture different aspects of platelet function and are therefore not interchangeable in the assessment of agonists´-induced platelet reactivity. Clinical outcome data are needed to determine which test systems and settings are associated with different in vivo consequences.http://europepmc.org/articles/PMC4461164?pdf=render
spellingShingle Thomas Gremmel
Renate Koppensteiner
Simon Panzer
Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
PLoS ONE
title Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
title_full Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
title_fullStr Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
title_full_unstemmed Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
title_short Comparison of Aggregometry with Flow Cytometry for the Assessment of Agonists´-Induced Platelet Reactivity in Patients on Dual Antiplatelet Therapy.
title_sort comparison of aggregometry with flow cytometry for the assessment of agonists´ induced platelet reactivity in patients on dual antiplatelet therapy
url http://europepmc.org/articles/PMC4461164?pdf=render
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AT simonpanzer comparisonofaggregometrywithflowcytometryfortheassessmentofagonistsinducedplateletreactivityinpatientsondualantiplatelettherapy