Thromboinflammation in COVID-19: Can α 2 -macroglobulin help to control the fire?

J Thromb Haemost. 2021 Feb;19(2):351-354. doi: 10.1111/jth.15190. Epub 2020 Dec 19.


The complex COVID-19-associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2 -macroglobulin (α2 -M) levels from severe COVID-19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone- and protease-coated web-like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and "versatile" inhibitor α2 -M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2 -M in COVID-19.

Keywords: COVID-19; endothelial cells; extracellular traps; neutrophil; thromboinflammation; α2-macroglobulin.

MeSH terms

  • Animals
  • Blood Coagulation
  • COVID-19 / complications
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • Endothelial Cells / metabolism
  • Extracellular Traps / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Inflammation / metabolism*
  • Inflammation / virology
  • Inflammation Mediators / metabolism
  • SARS-CoV-2 / pathogenicity*
  • Thrombosis / metabolism*
  • Thrombosis / virology
  • alpha-Macroglobulins / metabolism*


  • A2M protein, human
  • Inflammation Mediators
  • alpha-Macroglobulins