- Title
- NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia
- Creator
- Leung, Halina H. L.; Perdomo, Jose; Ahmadi, Zohra; Zheng, Shiying S.; Rashid, Fairooj N.; Enjeti, Anoop; Ting, Stephen B.; Chong, James J. H.; Chong, Beng H.
- Relation
- Nature Communications Vol. 13, Issue 1, no. 5206
- Publisher Link
- http://dx.doi.org/10.1038/s41467-022-32946-1
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19. The mechanisms involved in clot formation and thrombocytopenia in VITT are yet to be fully determined. Here we show neutrophils undergoing NETosis and confirm expression markers of NETs in VITT patients. VITT antibodies directly stimulate neutrophils to release NETs and induce thrombus formation containing abundant platelets, neutrophils, fibrin, extracellular DNA and citrullinated histone H3 in a flow microfluidics system and in vivo. Inhibition of NETosis prevents VITT-induced thrombosis in mice but not thrombocytopenia. In contrast, in vivo blockage of FcγRIIa abrogates both thrombosis and thrombocytopenia suggesting these are distinct processes. Our findings indicate that anti-PF4 antibodies activate blood cells via FcγRIIa and are responsible for thrombosis and thrombocytopenia in VITT. Future development of NETosis and FcγRIIa inhibitors are needed to treat VITT and similar immune thrombotic thrombocytopenia conditions more effectively, leading to better patient outcomes.
- Subject
- vaccine-induced immune thrombotic thrombocytopenia (VITT); NETosis; antibodies; thrombotic thrombocytopenia conditions; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1484387
- Identifier
- uon:51319
- Identifier
- ISSN:2041-1723
- Rights
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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