1. Alpha-defensins: risk factor for thrombosis in COVID-19 infection.
- Author
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Abdeen S, Bdeir K, Abu-Fanne R, Maraga E, Higazi M, Khurram N, Feldman M, Deshpande C, Litzky LA, Heyman SN, Montone KT, Cines DB, and Higazi AA
- Subjects
- Adult, Aged, Animals, Blood Coagulation drug effects, COVID-19 complications, COVID-19 diagnosis, COVID-19 virology, Case-Control Studies, Colchicine pharmacology, Female, Fibrin Fibrinogen Degradation Products analysis, Humans, Inflammation complications, Interleukin-6 blood, Interleukin-6 pharmacology, Male, Mice, Middle Aged, Models, Animal, Neutrophils drug effects, Prospective Studies, Risk Factors, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Severity of Illness Index, Thromboembolism etiology, Thrombosis etiology, Thrombosis metabolism, Tubulin Modulators pharmacology, alpha-Defensins pharmacology, COVID-19 metabolism, Inflammation metabolism, Thromboembolism prevention & control, alpha-Defensins blood
- 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., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2021
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