A Mathematical Model of Platelet Aggregation in an Extravascular Injury Under Flow
We present the first mathematical model of flow-mediated primary hemostasis in an extravascular injury, which can track the process from initial deposition to occlusion. The model consists of a system of ordinary differential equations (ODE) that describe platelet aggregation (adhesion and cohesion)...
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Main Authors | , , , , , |
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Format | Journal Article |
Language | English |
Published |
04.03.2020
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Subjects | |
Online Access | Get full text |
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Summary: | We present the first mathematical model of flow-mediated primary hemostasis
in an extravascular injury, which can track the process from initial deposition
to occlusion. The model consists of a system of ordinary differential equations
(ODE) that describe platelet aggregation (adhesion and cohesion),
soluble-agonist-dependent platelet activation, and the flow of blood through
the injury. The formation of platelet aggregates increases resistance to flow
through the injury, which is modeled using the Stokes-Brinkman equations. Data
from analogous experimental (microfluidic flow) and partial differential
equation models informed parameter values used in the ODE model description of
platelet adhesion, cohesion, and activation. This model predicts injury
occlusion under a range of flow and platelet activation conditions. Simulations
testing the effects of shear and activation rates resulted in delayed occlusion
and aggregate heterogeneity. These results validate our hypothesis that
flow-mediated dilution of activating chemical ADP hinders aggregate
development. This novel modeling framework can be extended to include more
mechanisms of platelet activation as well as the addition of the biochemical
reactions of coagulation, resulting in a computationally efficient high
throughput screening tool. |
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DOI: | 10.48550/arxiv.2003.02251 |