Thrombin activity confinement and dense granule release drive the dynamics of arterial thrombus
Efim S. Bershadsky, Dmitry Y. Nechipurenko
TL;DR
A new computational model explains how thrombin activity and platelet granule release control the structure and growth of arterial blood clots.
Contribution
A 3D computational model reveals how thrombin confinement and dense granule depletion regulate thrombus dynamics and structure.
Findings
Thrombus core size is regulated by thrombin transport and platelet activation thresholds.
ADP concentration dynamics and granule pool depletion explain three-stage thrombus growth.
The model explains reduced thrombus core size in Hermansky-Pudlak syndrome and hemostasis in penetrating injuries.
Abstract
The mechanisms driving spatial heterogeneity of arterial thrombus and its three-stage dynamics are poorly understood. To investigate the potential principles regulating the size of the thrombus core and shell we developed a 3D continuum computational model that describes thrombus heterogeneity, thrombin-induced platelet dense granule secretion and clot propagation through thrombin and ADP-induced platelet activation. The continuum model predicted that spatial confinement of the thrombus core was a result of thrombin transport and a threshold-like dependence of platelet activation on thrombin concentration. This new model recapitulated three-stage dynamics observed in vivo and explained it with a burst-like ADP concentration dynamics due to the confinement of thrombus core propagation and rapid dense granule pool depletion within the core. The maximal shell size in silico was regulated…
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Taxonomy
TopicsPlatelet Disorders and Treatments · Cerebrovascular and Carotid Artery Diseases · Cell Adhesion Molecules Research