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      ADAMTS13 activity to von Willebrand factor antigen ratio predicts acute kidney injury in patients with COVID‐19: Evidence of SARS‐CoV‐2 induced secondary thrombotic microangiopathy

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          Abstract

          Introduction

          Severe COVID‐19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID‐19 and for associations with disease progression and acute kidney injury (AKI).

          Methods

          Patients presenting to the emergency department (ED) with COVID‐19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI defined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30‐day COVID‐19 severity.

          Results

          A total of 52 adult COVID‐19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI ( P = .002) and those who developed the severe form of COVID‐19 ( P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age ( P < .001) and LDH ( P < .001), while positively correlated with hemoglobin ( P = .041). After controlling for confounders, a one‐unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI.

          Conclusion

          A low ADAMTS13 activity:VWF:Ag ratio at ED presentation is associated with progression to severe COVID‐19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID‐19.

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          Most cited references25

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

            Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
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              KDIGO Clinical Practice Guidelines for Acute Kidney Injury

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                Author and article information

                Contributors
                brandon.henry@cchmc.org
                Journal
                Int J Lab Hematol
                Int J Lab Hematol
                10.1111/(ISSN)1751-553X
                IJLH
                International Journal of Laboratory Hematology
                John Wiley and Sons Inc. (Hoboken )
                1751-5521
                1751-553X
                03 December 2020
                : 10.1111/ijlh.13415
                Affiliations
                [ 1 ] Cardiac Intensive Care Unit The Heart Institute Cincinnati Children's Hospital Medical Center Cincinnati OH USA
                [ 2 ] Division of Nephrology and Hypertension Cincinnati Children's Hospital Medical Center Cincinnati OH USA
                [ 3 ] Department of Pediatrics University of Cincinnati, College of Medicine Cincinnati OH USA
                [ 4 ] Department of Statistics Federal University of Parana Curitiba Brazil
                [ 5 ] Section of Clinical Biochemistry Department of Neuroscience, Biomedicine and Movement University of Verona Verona Italy
                [ 6 ] Haematology Sydney Centres for Thrombosis and Haemostasis Institute of Clinical Pathology and Medical Research (ICPMR) NSW Health Pathology Westmead Hospital Westmead NSW Australia
                [ 7 ] Department of Emergency Medicine University of Cincinnati Cincinnati OH USA
                Author notes
                [*] [* ] Correspondence

                Brandon Michael Henry, Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.

                Email: brandon.henry@ 123456cchmc.org

                Author information
                https://orcid.org/0000-0002-8047-338X
                https://orcid.org/0000-0001-9523-9054
                Article
                IJLH13415
                10.1111/ijlh.13415
                7753610
                33270980
                b2fc0bb9-b4a3-4334-b4a5-6ea115822efe
                © 2020 John Wiley & Sons Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 30 August 2020
                : 21 October 2020
                : 10 November 2020
                Page count
                Figures: 2, Tables: 3, Pages: 8, Words: 11988
                Funding
                Funded by: University of Cincinnati College of Medicine
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                Hematology
                acute kidney injury,adamts13,coagulopathy,outcome,thrombosis,von willebrand factor
                Hematology
                acute kidney injury, adamts13, coagulopathy, outcome, thrombosis, von willebrand factor

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