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新冠病毒感染合并肾损伤患者血栓形成的发病机制及早期抗凝治疗中的循环微颗粒

Circulating Microparticles in the Pathogenesis and Early Anticoagulation of Thrombosis in COVID-19 With Kidney Injury.

作者信息

Wang Chengyue, Yu Chengyuan, Novakovic Valerie A, Xie Rujuan, Shi Jialan

机构信息

Department of Hematology, The First Hospital of Harbin, Harbin Medical University, Harbin, China.

Department of Nephrology, The First Hospital of Harbin, Harbin Medical University, Harbin, China.

出版信息

Front Cell Dev Biol. 2022 Jan 18;9:784505. doi: 10.3389/fcell.2021.784505. eCollection 2021.

Abstract

As more is learned about the pathophysiological mechanisms of COVID-19, systemic thrombosis has been recognized as being associated with more severe clinical manifestations, mortality and sequelae. As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury, with coagulation abnormalities the main cause of impaired function. However, the mechanism of renal thrombosis and the process leading to kidney injury are unclear. Microparticles (MPs) are membrane bubbles released in response to activation, injury or apoptosis of cells. The phosphatidylserine (PS) exposed on the surface of MPs provides binding sites for endogenous and exogenous FXase complexes and prothrombin complexes, thus providing a platform for the coagulation cascade reaction and facilitating clot formation. In the context of COVID-19 infection, viral attack leads immune cells to release cytokines that damage circulating blood cells and vascular endothelial cells, resulting in increased MPs levels. Therefore, MPs can be used as a risk factor to predict renal microthrombosis and kidney injury. In this paper, we have summarized the latest data on the pathophysiological mechanism and treatment of renal thrombosis caused by MPs in COVID-19, revealing that the coagulation abnormality caused by MP and PS storms is a universal progression that aggravates the mortality and sequelae of COVID-19 and potentially other pandemic diseases. This paper also describes the risk factors affecting renal thrombosis in COVID-19 from the perspective of the Virchow's triad: blood hypercoagulability, vascular endothelial injury, and decreased blood flow velocity. In summary, given the serious consequences of thrombosis, current guidelines and clinical studies suggest that early prophylactic anticoagulant therapy reduces mortality and improves clinical outcomes. Early anticoagulation, through inhibition of PS-mediated coagulopathy, allows maintenance of unobstructed blood circulation and oxygen delivery thereby facilitating the removal of inflammatory factors, viruses, MPs, and dead or damaged cells, and expediting patient rehabilitation.

摘要

随着对新型冠状病毒肺炎(COVID-19)病理生理机制的了解越来越多,全身性血栓形成已被认为与更严重的临床表现、死亡率和后遗症相关。因COVID-19住院的患者中,多达40%患有急性肾损伤,凝血异常是功能受损的主要原因。然而,肾血栓形成的机制以及导致肾损伤的过程尚不清楚。微粒(MPs)是细胞在激活、损伤或凋亡时释放的膜泡。MPs表面暴露的磷脂酰丝氨酸(PS)为内源性和外源性FX酶复合物及凝血酶原复合物提供结合位点,从而为凝血级联反应提供平台并促进血栓形成。在COVID-19感染的情况下,病毒攻击导致免疫细胞释放细胞因子,损伤循环血细胞和血管内皮细胞,导致MPs水平升高。因此,MPs可作为预测肾微血栓形成和肾损伤的危险因素。在本文中,我们总结了关于COVID-19中MPs导致肾血栓形成的病理生理机制和治疗的最新数据,揭示了由MP和PS风暴引起的凝血异常是一个普遍的进展过程,会加重COVID-19以及可能其他大流行疾病的死亡率和后遗症。本文还从魏尔啸氏三联征的角度描述了影响COVID-19中肾血栓形成的危险因素:血液高凝性、血管内皮损伤和血流速度降低。总之,鉴于血栓形成的严重后果,当前指南和临床研究表明早期预防性抗凝治疗可降低死亡率并改善临床结局。早期抗凝通过抑制PS介导的凝血病,可维持血液循环和氧气输送通畅,从而促进炎症因子、病毒、MPs以及死亡或受损细胞的清除,并加快患者康复。

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