Novel assay demonstrates that coronary artery disease patients have heightened procoagulant platelet response

Novel assay demonstrates that coronary artery disease patients have heightened procoagulant platelet response.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Journal of Thrombosis and Haemostasis
Volume: 16
Number: 6
Page Range: pp. 1198-1210
Date: 2018
Divisions: ACRF Centenary Cancer Research Centre
Depositing User: General Admin
Identification Number: 10.1111/jth.14008
ISSN: 1538-7933
Date Deposited: 03 Jan 2021 22:31

Essentials Procoagulant platelets can be detected using GSAO in human whole blood. Stable coronary artery disease is associated with a heightened procoagulant platelet response. Agonist-induced procoagulant platelet response is not inhibited by aspirin alone. Collagen plus thrombin induced procoagulant platelet response is partially resistant to clopidogrel.

Summary: Background Procoagulant platelets are a subset of highly activated platelets with a critical role in thrombin generation. Evaluation of their clinical utility in thrombotic disorders, such as coronary artery disease (CAD), has been thwarted by the lack of a sensitive and specific whole blood assay. Objectives We developed a novel assay, utilizing the cell death marker, GSAO [(4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation marker, P-selectin, to identify procoagulant platelets in whole blood by flow cytometry. Patients/Methods Using this assay, we characterized the procoagulant platelet population in healthy controls and a cohort of patients undergoing elective coronary angiography. Results In patients with CAD, compared with patients without CAD, there was a heightened procoagulant platelet response to thrombin (25.2% vs. 12.2%), adenosine diphosphate (ADP) (7.8% vs. 2.7%) and thrombin plus collagen (27.2% vs. 18.3%). The heightened procoagulant platelet potential in CAD patients was not associated with other markers of platelet function, including aggregation, dense granule release and activation of α2b β3 integrin. Although dual antiplatelet therapy (DAPT) was associated with partial suppression of procoagulant platelets, this inhibitory effect on a patient level could not be predicted by aggregation response to ADP and was not fully suppressed by clopidogrel. Conclusions We report for the first time that procoagulant platelets can be efficiently detected in a few microliters of whole blood using the cell death marker, GSAO, and the platelet activation marker, P-selectin. A heightened procoagulant platelet response may provide insight into the thrombotic risk of CAD and help identify a novel target for antiplatelet therapies in CAD.

Keywords: coronary artery disease; flow cytometry; platelet activation; platelet aggregation inhibitors; platelet function studies; procoagulant platelets.

© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Pasalic, L.
Wing‐Lun, E.
Lau, J. K.
Campbell, H.
Pennings, G. J.
Lau, E.
Connor, D.
Liang, H. P.
Muller, D.
Kritharides, L.
Hogg, P. J.
Chen, V. M.
Last Modified: 03 Jan 2021 22:31

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