Alpha-defensins: risk factor for thrombosis in COVID-19 infection

Suhair Abdeen, Khalil Bdeir, Rami Abu-Fanne, Emad Maraga, Mohamed Higazi, Nigar Khurram, Michael Feldman, Charuhas Deshpande, Leslie A. Litzky, Samuel N. Heyman, Kathleen T. Montone, Douglas B. Cines, Abd Al Roof Higazi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The inflammatory response to SARS/CoV-2 (COVID-19) infection may contribute to the risk of thromboembolic complications. α-Defensins, antimicrobial peptides released from activated neutrophils, are anti-fibrinolytic and prothrombotic in vitro and in mouse models. In this prospective study of 176 patients with COVID-19 infection, we found that plasma levels of α-defensins were elevated, tracked with disease progression/mortality or resolution and with plasma levels of interleukin-6 (IL-6) and D-dimers. Immunohistochemistry revealed intense deposition of α-defensins in lung vasculature and thrombi. IL-6 stimulated the release of α-defensins from neutrophils, thereby accelerating coagulation and inhibiting fibrinolysis in human blood, imitating the coagulation pattern in COVID-19 patients. The procoagulant effect of IL-6 was inhibited by colchicine, which blocks neutrophil degranulation. These studies describe a link between inflammation and the risk of thromboembolism, and they identify a potential new approach to mitigate this risk in patients with COVID-19 and potentially in other inflammatory prothrombotic conditions.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalBritish Journal of Haematology
Volume194
Issue number1
DOIs
StatePublished - Jul 2021
Externally publishedYes

Keywords

  • COVID-19 infection
  • inflammation
  • interleukin-6
  • thrombosis
  • α-defensins

ASJC Scopus subject areas

  • Hematology

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