Li Yuan, Wang Hongyu, Xi Yifeng, Sun Anqiang, Deng Xiaoyan, Chen Zengsheng, Fan Yubo
Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
Bioengineering (Basel). 2022 May 27;9(6):235. doi: 10.3390/bioengineering9060235.
Thrombosis is the main complication in patients supported with ventricular assist devices (VAD). Models that accurately predict the risk of thrombus formation in VADs are still lacking. When VADs are clinically assisted, their complex geometric configuration and high rotating speed inevitably generate complex flow fields and high shear stress. These non-physiological factors can damage blood cells and proteins, release coagulant factors and trigger thrombosis. In this study, a more accurate model for thrombus assessment was constructed by integrating parameters such as shear stress, residence time and coagulant factors, so as to accurately assess the probability of thrombosis in three clinical VADs. A mathematical model was constructed to assess platelet activation and thrombosis within VADs. By solving the transport equation, the influence of various factors such as shear stress, residence time and coagulation factors on platelet activation was considered. The diffusion equation was applied to determine the role of activated platelets and substance deposition on thrombus formation. The momentum equation was introduced to describe the obstruction to blood flow when thrombus is formed, and finally a more comprehensive and accurate model for thrombus assessment in patients with VAD was obtained. Numerical simulations of three clinically VADs (CH-VAD, HVAD and HMII) were performed using this model. The simulation results were compared with experimental data on platelet activation caused by the three VADs. The simulated thrombogenic potential in different regions of MHII was compared with the frequency of thrombosis occurring in the regions in clinic. The regions of high thrombotic risk for HVAD and HMII observed in experiments were compared with the regions predicted by simulation. It was found that the percentage of activated platelets within the VAD obtained by solving the thrombosis model developed in this study was in high agreement with the experimental data (r² = 0.984), the likelihood of thrombosis in the regions of the simulation showed excellent correlation with the clinical statistics (r² = 0.994), and the regions of high thrombotic risk predicted by the simulation were consistent with the experimental results. Further study revealed that the three clinical VADs (CH-VAD, HVAD and HMII) were prone to thrombus formation in the inner side of the secondary flow passage, the clearance between cone and impeller, and the corner region of the inlet pipe, respectively. The risk of platelet activation and thrombus formation for the three VADs was low to high for CH-VAD, HVAD, and HM II, respectively. In this study, a more comprehensive and accurate thrombosis model was constructed by combining parameters such as shear stress, residence time, and coagulation factors. Simulation results of thrombotic risk received with this model showed excellent correlation with experimental and clinical data. It is important for determining the degree of platelet activation in VAD and identifying regions prone to thrombus formation, as well as guiding the optimal design of VAD and clinical treatment.
血栓形成是心室辅助装置（VAD）支持患者的主要并发症。目前仍缺乏能准确预测VAD中血栓形成风险的模型。当VAD用于临床辅助时，其复杂的几何结构和高转速不可避免地会产生复杂的流场和高剪切应力。这些非生理因素会损伤血细胞和蛋白质，释放凝血因子并引发血栓形成。在本研究中，通过整合剪切应力、停留时间和凝血因子等参数构建了一个更准确的血栓评估模型，以准确评估三种临床VAD中血栓形成的概率。构建了一个数学模型来评估VAD内血小板的活化和血栓形成。通过求解输运方程，考虑了剪切应力、停留时间和凝血因子等各种因素对血小板活化的影响。应用扩散方程确定活化血小板和物质沉积在血栓形成中的作用。引入动量方程来描述血栓形成时对血流的阻碍，最终获得了一个更全面、准确的VAD患者血栓评估模型。使用该模型对三种临床VAD（CH-VAD、HVAD和HMII）进行了数值模拟。将模拟结果与三种VAD引起的血小板活化实验数据进行了比较。将MHII不同区域的模拟血栓形成潜能与临床该区域血栓形成的频率进行了比较。将实验中观察到的HVAD和HMII高血栓形成风险区域与模拟预测区域进行了比较。结果发现，通过求解本研究建立的血栓形成模型得到的VAD内活化血小板百分比与实验数据高度吻合（r² = 0.984），模拟区域内血栓形成的可能性与临床统计数据显示出极好的相关性（r² = 0.994），模拟预测的高血栓形成风险区域与实验结果一致。进一步研究表明，三种临床VAD（CH-VAD、HVAD和HMII）分别在二次流道内侧、锥体与叶轮之间的间隙以及进水管拐角区域容易形成血栓。三种VAD的血小板活化和血栓形成风险分别为CH-VAD低、HVAD中、HM II高。在本研究中，通过结合剪切应力、停留时间和凝血因子等参数构建了一个更全面、准确的血栓形成模型。该模型得到的血栓形成风险模拟结果与实验和临床数据显示出极好的相关性。这对于确定VAD中血小板活化程度、识别易形成血栓的区域以及指导VAD的优化设计和临床治疗具有重要意义。
