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Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients

INTRODUCTION: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to...

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Autores principales: Lakshmanan, Hari Hara Sudhan, Pore, Adity A., Kohs, Tia C. L., Yazar, Feyza, Thompson, Rachel M., Jurney, Patrick L., Maddala, Jeevan, Olson, Sven R., Shatzel, Joseph J., Vanapalli, Siva A., McCarty, Owen J. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408976/
https://www.ncbi.nlm.nih.gov/pubmed/32837586
http://dx.doi.org/10.1007/s12195-020-00644-x
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author Lakshmanan, Hari Hara Sudhan
Pore, Adity A.
Kohs, Tia C. L.
Yazar, Feyza
Thompson, Rachel M.
Jurney, Patrick L.
Maddala, Jeevan
Olson, Sven R.
Shatzel, Joseph J.
Vanapalli, Siva A.
McCarty, Owen J. T.
author_facet Lakshmanan, Hari Hara Sudhan
Pore, Adity A.
Kohs, Tia C. L.
Yazar, Feyza
Thompson, Rachel M.
Jurney, Patrick L.
Maddala, Jeevan
Olson, Sven R.
Shatzel, Joseph J.
Vanapalli, Siva A.
McCarty, Owen J. T.
author_sort Lakshmanan, Hari Hara Sudhan
collection PubMed
description INTRODUCTION: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited in vitro methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials. Herein we present the design of a microfluidic “bleeding chip” to evaluate the effects of antithrombotic therapies on hemostatic plug formation in vitro. METHODS: The design of the microfluidic device consists of two orthogonal channels: an inlet that serves as a model blood vessel, and a bleeding channel to model hemostatic plug formation at sites of compromised endothelial barrier function. This is achieved by placing a series of 3 pillars spaced 10 μm apart at the intersection of the two channels. The pillars and bleeding channel are coated with the extracellular matrix protein collagen. RESULTS: Perfusion of human whole blood through the microfluidic bleeding chip led to initial platelet adhesion and aggregation at the pillars followed by hemostatic plug formation and occlusion of the bleeding channel. CONCLUSIONS: Safe and effective mitigating agents are needed for treatment and prevention of thrombotic complications in COVID-19 patients. This simple microfluidic device holds potential to be developed into a tool for assessing the effects of anticoagulant therapy on hemostasis.
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spelling pubmed-74089762020-08-07 Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients Lakshmanan, Hari Hara Sudhan Pore, Adity A. Kohs, Tia C. L. Yazar, Feyza Thompson, Rachel M. Jurney, Patrick L. Maddala, Jeevan Olson, Sven R. Shatzel, Joseph J. Vanapalli, Siva A. McCarty, Owen J. T. Cell Mol Bioeng Covid-19 INTRODUCTION: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited in vitro methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials. Herein we present the design of a microfluidic “bleeding chip” to evaluate the effects of antithrombotic therapies on hemostatic plug formation in vitro. METHODS: The design of the microfluidic device consists of two orthogonal channels: an inlet that serves as a model blood vessel, and a bleeding channel to model hemostatic plug formation at sites of compromised endothelial barrier function. This is achieved by placing a series of 3 pillars spaced 10 μm apart at the intersection of the two channels. The pillars and bleeding channel are coated with the extracellular matrix protein collagen. RESULTS: Perfusion of human whole blood through the microfluidic bleeding chip led to initial platelet adhesion and aggregation at the pillars followed by hemostatic plug formation and occlusion of the bleeding channel. CONCLUSIONS: Safe and effective mitigating agents are needed for treatment and prevention of thrombotic complications in COVID-19 patients. This simple microfluidic device holds potential to be developed into a tool for assessing the effects of anticoagulant therapy on hemostasis. Springer International Publishing 2020-08-06 /pmc/articles/PMC7408976/ /pubmed/32837586 http://dx.doi.org/10.1007/s12195-020-00644-x Text en © Biomedical Engineering Society 2020
spellingShingle Covid-19
Lakshmanan, Hari Hara Sudhan
Pore, Adity A.
Kohs, Tia C. L.
Yazar, Feyza
Thompson, Rachel M.
Jurney, Patrick L.
Maddala, Jeevan
Olson, Sven R.
Shatzel, Joseph J.
Vanapalli, Siva A.
McCarty, Owen J. T.
Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title_full Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title_fullStr Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title_full_unstemmed Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title_short Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients
title_sort design of a microfluidic bleeding chip to evaluate antithrombotic agents for use in covid-19 patients
topic Covid-19
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408976/
https://www.ncbi.nlm.nih.gov/pubmed/32837586
http://dx.doi.org/10.1007/s12195-020-00644-x
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