Evidence map›Paper›PMID 36064843›Full record

ArticleNature communications2022

NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia.

Halina H L Leung, Jose Perdomo, Zohra Ahmadi, Shiying S Zheng, Fairooj N Rashid, Anoop Enjeti, Stephen B Ting, James J H Chong, Beng H Chong

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 81 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Halina H L Leung *Haematology Research Unit, School of Clinical Medicine, St George and Sutherland Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0003-4959-3209
Jose Perdomo *Haematology Research Unit, School of Clinical Medicine, St George and Sutherland Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Zohra AhmadiHaematology Research Unit, School of Clinical Medicine, St George and Sutherland Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Shiying S ZhengHaematology Research Unit, School of Clinical Medicine, St George and Sutherland Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Fairooj N RashidSydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.ORCID 0000-0001-8319-7117
Anoop EnjetiCalvary Mater Hospital, Wallsend, NSW, Australia.
Stephen B TingDepartment of Haematology, Eastern Health and Monash University, Melbourne, VIC, Australia.ORCID 0000-0001-7755-8326
James J H ChongSydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.ORCID 0000-0002-5201-4856
Beng H ChongHaematology Research Unit, School of Clinical Medicine, St George and Sutherland Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. beng.chong@unsw.edu.au.ORCID 0000-0002-7561-490X
UNSW Sydney · AUNew South Wales Department of Health · AUThe University of Sydney · AUEastern Health · AUUniversity of Newcastle Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

COVID-19Extracellular TrapsPurpura, Thrombocytopenic, IdiopathicThrombocytopeniaThrombosisVaccinesAd26COVS1AnimalsChAdOx1 nCoV-19HumansMiceAd26COVS1ChAdOx1 nCoV-19Vaccines

Identifiers

PMID36064843
PMCPMC9441824
OpenAlexW4294606674

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.