Loss of pulsatility with continuous-flow left ventricular assist devices and the significance of the arterial endothelium in von-Willebrand factor production and degradation.
Loss of pulsatility with continuous-flow left ventricular assist devices and the significance of the arterial endothelium in von-Willebrand factor production and degradation.
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DOI：
10.1111/aor.14456
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发表时间：
2022-11
影响因子：
2.4
通讯作者：
G. Giridharan;Ian C. Berg;Esraa Ismail;Khanh T Nguyen;Jana Hecking;J. Kirklin;Xuanhong Cheng;P. Sethu
中科院分区：
文献类型：
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作者：
G. Giridharan;Ian C. Berg;Esraa Ismail;Khanh T Nguyen;Jana Hecking;J. Kirklin;Xuanhong Cheng;P. Sethu
背景使用连续流动心室辅助装置（CF-VAD）的患者发生获得性von-Willebrand综合征（AVWS）和非手术出血的风险较高。血管性血友病因子（vWF）通过血小板与受损内皮结合以促进凝血，在维持止血中起重要作用。在CF-VAD患者中，vWF降解为低MW多聚体，其在促进凝血方面效率低下，并且主要归因于与CF-VAD叶轮相关的超生理剪切应力。方法：在这篇综述中，我们评估了文献中关于表面固定化vWF在脉动流和连续流下的解开行为的信息，涉及：（A）动脉内皮vWF产生和释放到循环中的过程，（B）导致降解的表面结合vWF相对于可溶性vWF解开所需的临界剪切应力，以及（C）脉动性在vWF产生和降解中的作用。结果和结论综合起来，这些数据表明，脉动性的丧失及其对动脉内皮细胞的影响在vWF的产生、释放、解开和蛋白水解降解成低分子量多聚体中起着重要作用，有助于AVWS的发展。恢复搏动性可以通过预防AVWS和最大限度地降低非手术出血风险来缓解这一问题。
BACKGROUND Patients on continuous flow ventricular assist devices (CF-VADs) are at high risk for the development of Acquired von-Willebrand Syndrome (AVWS) and non-surgical bleeding. von Willebrand Factor (vWF) plays an essential role in maintaining hemostasis via platelet binding to the damaged endothelium to facilitate coagulation. In CF-VAD patients, degradation of vWF into low MW multimers that are inefficient in facilitating coagulation occurs and has been primarily attributed to the supraphysiological shear stress associated with the CF-VAD impeller. METHODS In this review, we evaluate information from the literature regarding the unraveling behavior of surface-immobilized vWF under pulsatile and continuous flow pertaining to: (A) the process of arterial endothelial vWF production and release into circulation, (B) the critical shear stress required to unravel surface bound versus soluble vWF which leads to degradation, and (C) the role of pulsatility in on the production and degradation of vWF. RESULTS AND CONCLUSION Taken together, these data suggests that the loss of pulsatility and its impact on arterial endothelial cells plays an important role in the production, release, unraveling, and proteolytic degradation of vWF into low MW multimers, contributing to the development of AVWS. Restoration of pulsatility can potentially mitigate this issue by preventing AVWS and minimizing the risk of non-surgical bleeding.