Novel stenotic microchannels to study thrombus formation in shear gradients: influence of shear forces and human platelet-related factors

Mathew Lui, Elizabeth E. Gardiner, Jane F. Arthur, Isaac Pinar, Woei Ming Lee, Kris Ryan, Josie Carberry, Robert K. Andrews

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50%, 70%, and 90% by area). Base wall shears between 1800 and 6600 s-1, and peak wall shears of 3700 to 29,000 s-1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.

Original languageEnglish
Article number2967
Number of pages10
JournalInternational Journal of Molecular Sciences
Volume20
Issue number12
DOIs
Publication statusPublished - 18 Jun 2019

Keywords

  • platelets
  • shear gradients
  • stenosis
  • thrombosis

Cite this

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title = "Novel stenotic microchannels to study thrombus formation in shear gradients: influence of shear forces and human platelet-related factors",
abstract = "Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50{\%}, 70{\%}, and 90{\%} by area). Base wall shears between 1800 and 6600 s-1, and peak wall shears of 3700 to 29,000 s-1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.",
keywords = "platelets, shear gradients, stenosis, thrombosis",
author = "Mathew Lui and Gardiner, {Elizabeth E.} and Arthur, {Jane F.} and Isaac Pinar and Lee, {Woei Ming} and Kris Ryan and Josie Carberry and Andrews, {Robert K.}",
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Novel stenotic microchannels to study thrombus formation in shear gradients : influence of shear forces and human platelet-related factors. / Lui, Mathew; Gardiner, Elizabeth E.; Arthur, Jane F.; Pinar, Isaac; Lee, Woei Ming; Ryan, Kris; Carberry, Josie; Andrews, Robert K.

In: International Journal of Molecular Sciences, Vol. 20, No. 12, 2967, 18.06.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Novel stenotic microchannels to study thrombus formation in shear gradients

T2 - influence of shear forces and human platelet-related factors

AU - Lui, Mathew

AU - Gardiner, Elizabeth E.

AU - Arthur, Jane F.

AU - Pinar, Isaac

AU - Lee, Woei Ming

AU - Ryan, Kris

AU - Carberry, Josie

AU - Andrews, Robert K.

PY - 2019/6/18

Y1 - 2019/6/18

N2 - Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50%, 70%, and 90% by area). Base wall shears between 1800 and 6600 s-1, and peak wall shears of 3700 to 29,000 s-1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.

AB - Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear. Human platelets in anticoagulated whole blood were exposed ex vivo to collagen type I-coated microchannels subjected to constant shear in straight channels or variable shear gradients using different stenosis geometries (50%, 70%, and 90% by area). Base wall shears between 1800 and 6600 s-1, and peak wall shears of 3700 to 29,000 s-1 within stenoses were investigated, representing arterial-pathological shear conditions. Computational flow-field simulations and stenosis platelet thrombi total volume, average volume, and surface coverage were analysed. Interestingly, shear gradients dramatically changed platelet thrombi formation compared to constant base shear alone. Such shear gradients extended the range of shear at which thrombi were formed, that is, platelets became hyperthrombotic within shear gradients. Furthermore, individual healthy donors displayed quantifiable differences in extent/formation of thrombi within shear gradients, with implications for future development and testing of antiplatelet agents. In conclusion, here, we demonstrate a specific contribution of blood flow shear gradients to thrombus formation, and provide a novel platform for platelet functional testing under shear conditions.

KW - platelets

KW - shear gradients

KW - stenosis

KW - thrombosis

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U2 - 10.3390/ijms20122967

DO - 10.3390/ijms20122967

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 12

M1 - 2967

ER -