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

doi:10.1111/bjh.17503

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

Pathology

Research output: Contribution to journal › Article › peer-review

14 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 language	English (US)
Pages (from-to)	44-52
Number of pages	9
Journal	British Journal of Haematology
Volume	194
Issue number	1
DOIs	https://doi.org/10.1111/bjh.17503
State	Published - Jul 2021

Keywords

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

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/bjh.17503

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title = "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.",

keywords = "COVID-19 infection, inflammation, interleukin-6, thrombosis, α-defensins",

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

note = "Funding Information: This research was supported by grants from the Israeli Science Foundation ISF: 930/04 and 3959/19 (AH), and NIH grants DK113142 and HL123912 (DBC) and a grant from the University of Pennsylvania Institute for Translational Medicine and Therapeutics Transdisciplinary Program in Translational Medicine and Therapeutics (KB). We thank Daniel Martinez and the Pathology Core Laboratory at the Childrens Hospital of Philadelphia Research Institute for providing immunohistochemistry and digital slide scanning services. Publisher Copyright: {\textcopyright} 2021 British Society for Haematology and John Wiley & Sons Ltd",

year = "2021",

month = jul,

doi = "10.1111/bjh.17503",

language = "English (US)",

volume = "194",

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T2 - risk factor for thrombosis in COVID-19 infection

AU - Abdeen, Suhair

AU - Bdeir, Khalil

AU - Abu-Fanne, Rami

AU - Maraga, Emad

AU - Higazi, Mohamed

AU - Khurram, Nigar

AU - Feldman, Michael

AU - Deshpande, Charuhas

AU - Litzky, Leslie A.

AU - Heyman, Samuel N.

AU - Montone, Kathleen T.

AU - Cines, Douglas B.

AU - Higazi, Abd Al Roof

N1 - Funding Information: This research was supported by grants from the Israeli Science Foundation ISF: 930/04 and 3959/19 (AH), and NIH grants DK113142 and HL123912 (DBC) and a grant from the University of Pennsylvania Institute for Translational Medicine and Therapeutics Transdisciplinary Program in Translational Medicine and Therapeutics (KB). We thank Daniel Martinez and the Pathology Core Laboratory at the Childrens Hospital of Philadelphia Research Institute for providing immunohistochemistry and digital slide scanning services. Publisher Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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