Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality
- 15 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Angiogenesis
- Vol. 24 (3), 505-517
- https://doi.org/10.1007/s10456-020-09762-6
Abstract
Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. Objectives To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. Methods Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission. Results Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428–596) compared to non-critical patients (288%, 230–350, p < 0.0001) or COVID-19 outpatients (144%, 133–198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86–1.09) compared to non-critical patients (0.96, 1.04–1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan–Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and d-dimer levels. Conclusion VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.Keywords
Funding Information
- ANR (SARCODO)
- AP-HP
This publication has 48 references indexed in Scilit:
- Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysisCritical Care, 2015
- Prehospital Aspirin Use Is Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill PatientsCritical Care Medicine, 2015
- Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort StudyCritical Care Research and Practice, 2013
- Antiplatelet Therapy Is Associated With Decreased Transfusion-Associated Risk of Lung Dysfunction, Multiple Organ Failure, and Mortality in Trauma Patients*Critical Care Medicine, 2013
- von Willebrand factor: the old, the new and the unknownJournal of Thrombosis and Haemostasis, 2012
- Standardization of von Willebrand factor propeptide: value assignment to the WHO 6th IS Factor VIII/von Willebrand factor, plasma (07/316)Journal of Thrombosis and Haemostasis, 2012
- Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?Thrombosis, 2011
- Dexamethasone Arterializes Venous Endothelial Cells by Inducing Mitogen-Activated Protein Kinase Phosphatase-1Circulation, 2011
- Glucocorticoids Increase VE-Cadherin Expression and Cause Cytoskeletal Rearrangements in Murine Brain Endothelial cEND CellsJournal of Cerebral Blood Flow & Metabolism, 2008
- ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditionsBlood, 2002