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.

Highlights

  • As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury (AKI) (Blum, et al, 2020), and these patients have more serious clinical manifestations and mortality (Zheng, et al, 2020; Chebotareva, et al, 2021)

  • A study showed that in critically ill COVID-19 patients, compared with usual-care pharmacologic thromboprophylaxis, therapeutic-dose anticoagulation with heparin did not lead to greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support (REMAP-CAP Investigators et al, 2021a)

  • Knowing pathophysiological role of MPs in COVID-19 renal thrombosis has enhanced our understanding of the relationship between viruses and coagulation and will help formulate effective anticoagulation strategies

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Summary

Introduction

As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury (AKI) (Blum, et al, 2020), and these patients have more serious clinical manifestations and mortality (Zheng, et al, 2020; Chebotareva, et al, 2021). SARS-CoV-2 destroys circulating blood cells, renal capillary endothelial cells and podocytes, releasing great amounts of PS+ MPs, leading to the production of thrombin, increased blood viscosity, and promoting renal thrombosis.

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