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Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease
Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has dem...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448376/ https://www.ncbi.nlm.nih.gov/pubmed/34491991 http://dx.doi.org/10.1371/journal.pcbi.1009331 |
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author | Grande Gutiérrez, Noelia Alber, Mark Kahn, Andrew M. Burns, Jane C. Mathew, Mathew McCrindle, Brian W. Marsden, Alison L. |
author_facet | Grande Gutiérrez, Noelia Alber, Mark Kahn, Andrew M. Burns, Jane C. Mathew, Mathew McCrindle, Brian W. Marsden, Alison L. |
author_sort | Grande Gutiérrez, Noelia |
collection | PubMed |
description | Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case—mechanical or biochemical—could help define improved strategies for thrombosis prevention tailored for each patient. |
format | Online Article Text |
id | pubmed-8448376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84483762021-09-18 Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease Grande Gutiérrez, Noelia Alber, Mark Kahn, Andrew M. Burns, Jane C. Mathew, Mathew McCrindle, Brian W. Marsden, Alison L. PLoS Comput Biol Research Article Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case—mechanical or biochemical—could help define improved strategies for thrombosis prevention tailored for each patient. Public Library of Science 2021-09-07 /pmc/articles/PMC8448376/ /pubmed/34491991 http://dx.doi.org/10.1371/journal.pcbi.1009331 Text en © 2021 Grande Gutiérrez et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Grande Gutiérrez, Noelia Alber, Mark Kahn, Andrew M. Burns, Jane C. Mathew, Mathew McCrindle, Brian W. Marsden, Alison L. Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title | Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title_full | Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title_fullStr | Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title_full_unstemmed | Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title_short | Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease |
title_sort | computational modeling of blood component transport related to coronary artery thrombosis in kawasaki disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448376/ https://www.ncbi.nlm.nih.gov/pubmed/34491991 http://dx.doi.org/10.1371/journal.pcbi.1009331 |
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