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Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk

Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and ar...

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Autores principales: Ting, Lucas H., Feghhi, Shirin, Taparia, Nikita, Smith, Annie O., Karchin, Ari, Lim, Esther, John, Alex St., Wang, Xu, Rue, Tessa, White, Nathan J., Sniadecki, Nathan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416331/
https://www.ncbi.nlm.nih.gov/pubmed/30867419
http://dx.doi.org/10.1038/s41467-019-09150-9
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author Ting, Lucas H.
Feghhi, Shirin
Taparia, Nikita
Smith, Annie O.
Karchin, Ari
Lim, Esther
John, Alex St.
Wang, Xu
Rue, Tessa
White, Nathan J.
Sniadecki, Nathan J.
author_facet Ting, Lucas H.
Feghhi, Shirin
Taparia, Nikita
Smith, Annie O.
Karchin, Ari
Lim, Esther
John, Alex St.
Wang, Xu
Rue, Tessa
White, Nathan J.
Sniadecki, Nathan J.
author_sort Ting, Lucas H.
collection PubMed
description Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin α(IIb)β(3,) P2Y(12), or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk.
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spelling pubmed-64163312019-03-15 Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk Ting, Lucas H. Feghhi, Shirin Taparia, Nikita Smith, Annie O. Karchin, Ari Lim, Esther John, Alex St. Wang, Xu Rue, Tessa White, Nathan J. Sniadecki, Nathan J. Nat Commun Article Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin α(IIb)β(3,) P2Y(12), or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk. Nature Publishing Group UK 2019-03-13 /pmc/articles/PMC6416331/ /pubmed/30867419 http://dx.doi.org/10.1038/s41467-019-09150-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ting, Lucas H.
Feghhi, Shirin
Taparia, Nikita
Smith, Annie O.
Karchin, Ari
Lim, Esther
John, Alex St.
Wang, Xu
Rue, Tessa
White, Nathan J.
Sniadecki, Nathan J.
Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title_full Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title_fullStr Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title_full_unstemmed Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title_short Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
title_sort contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416331/
https://www.ncbi.nlm.nih.gov/pubmed/30867419
http://dx.doi.org/10.1038/s41467-019-09150-9
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