Grow with the flow: a spatial-temporal model of platelet deposition and blood coagulation under flow
Grow with the flow: a spatial-temporal model of platelet deposition and blood coagulation under flow
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DOI：
10.1093/imammb/dqq005
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发表时间：
2011-03-01
影响因子：
1.1
通讯作者：
Fogelson, Aaron L.
中科院分区：
文献类型：
--
作者：
Leiderman, Karin;Fogelson, Aaron L.
人体对血管损伤的反应涉及两个相互交织的过程：血小板聚集和凝结。血小板聚集是一个主要的物理过程，血小板将血小板凝结在一起，而凝结是一系列生化酶反应的级联。凝血蛋白是凝血的主要产物，通过激活血小板并将纤维蛋白原裂解为纤维蛋白单体，直接将生化系统与血小板聚集耦合，从而形成稳定血小板聚集物的网状。纤维蛋白网格和血小板聚集体共同包含一个可以生长至闭塞直径的血栓。凝血蛋白和血小板往返损伤的运输主要由血流的动力学控制。为了探索血流如何影响血栓的生长以及如何反过来，反馈和影响流动，我们开发了第一个空间 - 周期性数学模型的血小板聚集和血液凝结在流动下，包括凝结的详细描述血小板的生物化学，化学激活和沉积，以及流体动力学与增长的血小板质量之间的双向相互作用。我们提出了该模型，并使用它来解释凝血系统产生凝血酶的阈值行为的基础，并显示壁剪切速率和近壁增强的血小板浓度如何影响增长的血栓的发展。通过考虑血栓的多孔性质，我们还证明了对流和扩散的运输如何在血栓上以及在不同阶段和空间位置影响其生长。
The body's response to vascular injury involves two intertwined processes: platelet aggregation and coagulation. Platelet aggregation is a predominantly physical process, whereby platelets clump together, and coagulation is a cascade of biochemical enzyme reactions. Thrombin, the major product of coagulation, directly couples the biochemical system to platelet aggregation by activating platelets and by cleaving fibrinogen into fibrin monomers that polymerize to form a mesh that stabilizes platelet aggregates. Together, the fibrin mesh and the platelet aggregates comprise a thrombus that can grow to occlusive diameters. Transport of coagulation proteins and platelets to and from an injury is controlled largely by the dynamics of the blood flow. To explore how blood flow affects the growth of thrombi and how the growing masses, in turn, feed back and affect the flow, we have developed the first spatial-temporal mathematical model of platelet aggregation and blood coagulation under flow that includes detailed descriptions of coagulation biochemistry, chemical activation and deposition of blood platelets, as well as the two-way interaction between the fluid dynamics and the growing platelet mass. We present this model and use it to explain what underlies the threshold behaviour of the coagulation system's production of thrombin and to show how wall shear rate and near-wall enhanced platelet concentrations affect the development of growing thrombi. By accounting for the porous nature of the thrombus, we also demonstrate how advective and diffusive transport to and within the thrombus affects its growth at different stages and spatial locations.