Platelet Transport Rates and Binding Kinetics at High Shear over a Thrombus

Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used...

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Bibliographic Details
Published in:Biophysical journal 2013-07, Vol.105 (2), p.502-511
Main Authors: Bark, David L., Ku, David N.
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis
Biophysics
Blood platelets
Blood Platelets - physiology
Cell Movement
Coronary Thrombosis - pathology
Erythrocytes - physiology
Hemodynamics
Humans
Kinetics
Models, Biological
Platelet Adhesiveness
Platelet Aggregation
Systems Biophysics
Thrombosis
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Summary:Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s−1. Above 7000 s−1, the thrombus growth rate is likely limited by binding kinetics (10−4 m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2013.05.049