Mesoscale Simulations of Blood Coagulation in Flow and Quiescent Domains Using SDPD

IF 2.1 4区 医学 Q3 ENGINEERING, BIOMEDICAL
Marina Echeverría Ferrero, Nicolas Moreno, Marco Ellero
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Abstract

Blood coagulation is governed by tightly regulated reaction networks whose activation and early evolution are influenced by transport processes. While reduced kinetic models of the intrinsic and extrinsic pathways have been validated in well-mixed experimental settings, their behavior in spatially resolved domains remains insufficiently characterized. In this work, two established reduced coagulation networks are embedded within a thermodynamically consistent mesoscale particle-based framework that resolves fluid momentum transport together with multispecies advection–diffusion–reaction dynamics. Unlike conventional continuum coagulation solvers, the proposed formulation captures coupled transport and biochemical interactions through interacting particles within a unified hydrodynamic description. The framework is used to investigate the initiation phase of coagulation under controlled microvascular-like flow conditions in simplified channel geometries. The simulations reproduce characteristic thrombin generation curves (TGCs) across physiologically relevant parameter ranges while additionally revealing spatial transport effects that are not captured by outlet-averaged measures alone. In particular, the results show that transport–reaction coupling induces pronounced spatial heterogeneities in thrombin concentration, with transitions between localized activation, wall-aligned accumulation, and advective washout depending on Reynolds and Péclet regimes. Injury geometry is further shown to modulate coagulation amplification, with capped configurations producing enhanced thrombin accumulation due to localized surface-mediated activation. Complementary quiescent-domain simulations additionally reproduce qualitative trends observed in thrombodynamics assays, including fibrinogen-dependent variations in fibrin formation. Overall, the study introduces a unified mesoscale computational framework for analyzing how flow, transport, and biochemical kinetics jointly regulate early coagulation dynamics in spatially resolved domains.

血液凝固在流动和静止区域的中尺度模拟。
血液凝固受严密调控的反应网络控制,反应网络的激活和早期演化受运输过程的影响。虽然内源性和外源性途径的简化动力学模型已经在混合良好的实验环境中得到验证,但它们在空间分辨域中的行为仍然没有充分表征。在这项工作中,两个已建立的还原混凝网络嵌入在一个热力学一致的基于中尺度粒子的框架中,该框架解决了流体动量输运以及多物种平流-扩散-反应动力学。与传统的连续介质混凝溶液不同,所提出的配方通过在统一的流体动力学描述中相互作用的粒子捕获耦合输运和生化相互作用。该框架用于研究在简化通道几何形状的受控微血管样流动条件下凝血的起始阶段。模拟再现了生理相关参数范围内凝血酶生成曲线(TGCs)的特征,同时还揭示了仅通过出口平均测量无法捕获的空间传输效应。特别是,研究结果表明,转运-反应耦合导致凝血酶浓度的明显空间异质性,在局部激活、壁面积聚和顺流冲刷之间发生转变,这取决于Reynolds和psamclet制度。损伤几何进一步显示调节凝血放大,帽状结构产生增强凝血酶积累由于局部表面介导的激活。互补的静态域模拟还再现了在血栓动力学分析中观察到的定性趋势,包括纤维蛋白形成中纤维蛋白原依赖的变化。总体而言,该研究引入了一个统一的中尺度计算框架,用于分析流动、输运和生化动力学如何在空间分辨域中共同调节早期凝血动力学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International Journal for Numerical Methods in Biomedical Engineering
International Journal for Numerical Methods in Biomedical Engineering ENGINEERING, BIOMEDICAL-MATHEMATICAL & COMPUTATIONAL BIOLOGY
CiteScore
4.50
自引率
9.50%
发文量
103
审稿时长
3 months
期刊介绍: All differential equation based models for biomedical applications and their novel solutions (using either established numerical methods such as finite difference, finite element and finite volume methods or new numerical methods) are within the scope of this journal. Manuscripts with experimental and analytical themes are also welcome if a component of the paper deals with numerical methods. Special cases that may not involve differential equations such as image processing, meshing and artificial intelligence are within the scope. Any research that is broadly linked to the wellbeing of the human body, either directly or indirectly, is also within the scope of this journal.
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