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Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s

Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s
Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s.

METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s.

RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2 = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier.

CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

Acute Coronary Syndrome/blood, Adolescent, Adult, Aged, Area Under Curve, Case-Control Studies, Clopidogrel, Drug Monitoring/methods, Female, Humans, Male, Middle Aged, Platelet Activation/drug effects, Platelet Aggregation Inhibitors/adverse effects, Predictive Value of Tests, Prospective Studies, Purinergic P2Y Receptor Antagonists/adverse effects, ROC Curve, Reproducibility of Results, Thrombelastography, Ticlopidine/adverse effects, Time Factors, Whole Blood Coagulation Time, Young Adult
1755-5914
1-25
Olechowski, Bartosz
b025b40b-f9fa-4b8e-8f57-310d47e57700
Dalton, Richard T.
22502b2a-837e-44b0-ab88-17804a1cb995
Khanna, Vikram
17b557ad-b071-4d1a-84dd-3ba58470cee0
Ashby, Alexander
f403fd28-7991-4d70-96c5-9dccdf339e32
Vavyla, Maria
b6e562a5-a052-4a3c-950e-52d1b66c6a8b
Mariathas, Mark
e8dbbe0d-d303-41a4-a5a2-fa8900accfe6
Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Nicholas, Zoe
98403583-c418-45ad-836b-1831517dcc5f
Mahmoudi, Michael
f6a55246-399e-4f81-944e-a4b169786e8a
Curzen, Nick
70f3ea49-51b1-418f-8e56-8210aef1abf4
Olechowski, Bartosz
b025b40b-f9fa-4b8e-8f57-310d47e57700
Dalton, Richard T.
22502b2a-837e-44b0-ab88-17804a1cb995
Khanna, Vikram
17b557ad-b071-4d1a-84dd-3ba58470cee0
Ashby, Alexander
f403fd28-7991-4d70-96c5-9dccdf339e32
Vavyla, Maria
b6e562a5-a052-4a3c-950e-52d1b66c6a8b
Mariathas, Mark
e8dbbe0d-d303-41a4-a5a2-fa8900accfe6
Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Nicholas, Zoe
98403583-c418-45ad-836b-1831517dcc5f
Mahmoudi, Michael
f6a55246-399e-4f81-944e-a4b169786e8a
Curzen, Nick
70f3ea49-51b1-418f-8e56-8210aef1abf4

Olechowski, Bartosz, Dalton, Richard T., Khanna, Vikram, Ashby, Alexander, Vavyla, Maria, Mariathas, Mark, Harris, Scott, Nicholas, Zoe, Mahmoudi, Michael and Curzen, Nick (2018) Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s. Cardiovascular therapeutics, 36 (4), 1-25, [e12433]. (doi:10.1111/1755-5922.12433).

Record type: Article

Abstract

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s.

METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s.

RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2 = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier.

CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

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Olechowski_et_al-2018-Cardiovascular_Therapeutics - Accepted Manuscript
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Accepted/In Press date: 9 April 2018
e-pub ahead of print date: 22 April 2018
Published date: August 2018
Keywords: Acute Coronary Syndrome/blood, Adolescent, Adult, Aged, Area Under Curve, Case-Control Studies, Clopidogrel, Drug Monitoring/methods, Female, Humans, Male, Middle Aged, Platelet Activation/drug effects, Platelet Aggregation Inhibitors/adverse effects, Predictive Value of Tests, Prospective Studies, Purinergic P2Y Receptor Antagonists/adverse effects, ROC Curve, Reproducibility of Results, Thrombelastography, Ticlopidine/adverse effects, Time Factors, Whole Blood Coagulation Time, Young Adult

Identifiers

Local EPrints ID: 420945
URI: http://eprints.soton.ac.uk/id/eprint/420945
ISSN: 1755-5914
PURE UUID: ffd8ded3-9031-4de2-9a97-ed1a737d4c9c
ORCID for Michael Mahmoudi: ORCID iD orcid.org/0000-0003-1293-8461
ORCID for Nick Curzen: ORCID iD orcid.org/0000-0001-9651-7829

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Date deposited: 18 May 2018 16:30
Last modified: 16 Mar 2024 06:36

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Contributors

Author: Bartosz Olechowski
Author: Richard T. Dalton
Author: Vikram Khanna
Author: Alexander Ashby
Author: Maria Vavyla
Author: Mark Mariathas
Author: Scott Harris
Author: Zoe Nicholas
Author: Nick Curzen ORCID iD

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