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

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.

• Authors: 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
• Journal: British journal of haematology (Br J Haematol) Vol. 194 Issue 1 Pg. 44-52 (07 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 34053084 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Fibrin Fibrinogen Degradation Products
• Interleukin-6
• Tubulin Modulators
• alpha-Defensins
• fibrin fragment D
• Colchicine

Topics

• Adult
• Aged
• Animals
• Blood Coagulation (drug effects)
• COVID-19 (complications, diagnosis, metabolism, virology)
• Case-Control Studies
• Colchicine (pharmacology)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Humans
• Inflammation (complications, metabolism)
• Interleukin-6 (blood, pharmacology)
• Male
• Mice
• Middle Aged
• Models, Animal
• Neutrophils (drug effects)
• Prospective Studies
• Risk Factors
• SARS-CoV-2 (genetics, isolation & purification)
• Severity of Illness Index
• Thromboembolism (etiology, prevention & control)
• Thrombosis (etiology, metabolism)
• Tubulin Modulators (pharmacology)
• alpha-Defensins (blood, pharmacology)