Computational model of device-induced thrombosis and thromboembolism

Computational model of device-induced thrombosis and thromboembolism
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DOI:
10.1007/s10439-005-2951-z
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发表时间:
2005-06-01
影响因子:
3.8
通讯作者:
Solen, KA
Solen, KA
中科院分区:
工程技术2区
文献类型:
--
作者:
Goodman, PD;Barlow, ET;Solen, KA

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提出了一个血栓形成/血栓栓塞(T/TE)的数值模型,该模型预测了低剪切装置(血液透析器、氧合器等)中血栓生长和血栓栓塞的进展。通过求解耦合的对流-扩散-反应方程来预测流速、血小板激动剂(ADP、血栓素A2和凝血酶)浓度、激动剂诱导和剪切诱导的血小板活化、血小板运输和粘附到生物材料表面和粘附血小板(因此,血栓生长)。单血小板和血栓栓塞预测剪切力和表面粘附强度。血小板-生物材料反应常数和血小板粘附强度的值是在特定实验中测量的,但所有其他参数值均来自已发表的资料。该模型生成连续时间步骤的解决方案,同时调整速度模式以适应不断增长的表面血栓。将肝素化的人血以0.75 ml/min的速度灌注580 μ m-ID的聚乙烯流细胞(280 μ m-ID)。通过视频显微镜观察血栓的形成、生长和栓塞,光散射证实栓塞,扫描电镜观察血小板粘附。数值预测和实验观察结果在以下方面是相似的:1)流动细胞中相同的三个血栓形成位置以及这些位置血栓形成的相对顺序;2)在聚乙烯和硅橡胶上相同的血栓生长速度(尽管总体T/TE不同);3)流速(1.5 ml/min vs 0.75 ml/min)对血小板粘附和血栓形成模式的影响相似。
A numerical model of thrombosis/thromboembolism (T/TE) is presented that predicts the progression of thrombus growth and thromboembolization in low-shear devices (hemodialyzers, oxygenators, etc.). Coupled convection-diffusion-reaction equations were solved to predict velocities, platelet agonist (ADP, thromboxane A2, and thrombin) concentrations, agonist-induced and shear-induced platelet activation, and platelet transport and adhesion to biomaterial surfaces and adherent platelets (hence, thrombus growth). Single-platelet and thrombus embolization were predicted from shear forces and surface adhesion strengths. Values for the platelet-biomaterial reaction constant and the platelet adhesion strength were measured in specific experiments, but all other parameter values were obtained from published sources. The model generated solutions for sequential time steps, while adjusting velocity patterns to accommodate growing surface thrombi.Heparinized human blood was perfused (0.75 ml/min) through 580 mu m-ID polyethylene flow cells with flow contractions (280 mu m-ID). Thrombus initiation, growth, and embolization were observed with videomicroscopy, while embolization was confirmed by light scattering, and platelet adhesion was determined by scanning electron microscopy.Numerical predictions and experimental observations were similar in indicating: 1) the same three thrombotic locations in the flow cell and the relative order of thrombus development in those locations, 2) equal thrombus growth rates on polyethylene and silicon rubber (in spite of differing overall T/TE), and 3) similar effects of flow rate (1.5 ml/min versus 0.75 ml/min) on platelet adhesion and thrombosis patterns.