A MATHEMATICAL MODEL OF PLATELET AGGREGATION IN AN EXTRAVASCULAR INJURY UNDER FLOW.
A MATHEMATICAL MODEL OF PLATELET AGGREGATION IN AN EXTRAVASCULAR INJURY UNDER FLOW.
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DOI：
10.1137/20m1317785
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fogelson AL
中科院分区：
文献类型：
--
作者：
Link KG;Sorrells MG;Danes NA;Neeves KB;Leiderman K;Fogelson AL
我们提出了第一个血管外损伤中血流介导的原发性止血的数学模型，该模型可以跟踪从初始沉积到闭塞的过程。该模型由一个常微分方程（ode）系统组成，该系统描述了血小板聚集（粘附和内聚），可溶性激动剂依赖性血小板激活以及通过损伤的血流。血小板聚集体的形成增加了流过损伤的阻力，这是用Stokes-Brinkman方程建模的。来自类似实验（微流体流动）和偏微分方程模型的数据为ODE模型描述血小板粘附、内聚和活化中使用的参数值提供了信息。该模型预测了一系列血流和血小板活化条件下的损伤闭塞。模拟测试剪切和激活率的影响导致延迟闭塞和聚集体异质性。这些结果验证了我们的假设，即流动介导的激活化学二磷酸腺苷的稀释阻碍了聚集体的发育。这种新颖的建模框架可以扩展到包括更多的血小板活化机制以及凝血的生化反应，从而产生一种计算效率高的原发性和继发性止血的高通量筛选工具。
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 (ODEs) 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 adenosine diphosphate 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 of primary and secondary hemostasis.
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影响因子：
20.1
作者：
Bledzka K;Smyth SS;Plow EF
通讯作者：
Plow EF
影响因子：
5
作者：
Baurand, A;Raboisson, P;Gachet, C
通讯作者：
Gachet, C
影响因子：
10.4
作者：
Jackson, SP;Nesbitt, WS;Kulkarni, S
通讯作者：
Kulkarni, S
影响因子：
2.1
作者：
GEAR, ARL
通讯作者：
GEAR, ARL
DOI：
10.1093/imammb/dqq005
发表时间：
2011-03-01
影响因子：
1.1
作者：
Leiderman, Karin;Fogelson, Aaron L.
通讯作者：
Fogelson, Aaron L.