Thromb Haemost 2020; 120(12): 1668-1679
DOI: 10.1055/s-0040-1715841
Review Article

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

Upendra K. Katneni
1   Department of Pediatrics, The Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, Maryland, United States
Aikaterini Alexaki
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
Ryan C. Hunt
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
Tal Schiller
3   Diabetes, Endocrinology and Metabolic Disease Unit, Kaplan Medical Center, Rehovot, Israel
Michael DiCuccio
4   National Center of Biotechnology Information, National Institutes of Health, Bethesda, Maryland, United States
Paul W. Buehler
1   Department of Pediatrics, The Center for Blood Oxygen Transport and Hemostasis, University of Maryland School of Medicine, Baltimore, Maryland, United States
Juan C. Ibla
5   Division of Cardiac Anesthesia, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, United States
Chava Kimchi-Sarfaty
2   Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation & Research, U.S. FDA, Silver Spring, Maryland, United States
› Author Affiliations
Funding This work was partly supported by funds from the Hemostasis Branch/Division of Plasma Protein Therapeutics/Office of Tissues and Advanced Therapies/Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration. This research was also supported by the Intramural Research Program of the National Library of Medicine at the NIH.


Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.

Publication History

Received: 14 May 2020

Accepted: 14 July 2020

Article published online:
24 August 2020

© 2020. Thieme. All rights reserved.

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