Evidence map›Paper›PMID 30899022›Full record

ArticleNature communications2019

Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia.

José Perdomo, Halina H L Leung, Zohra Ahmadi, Feng Yan, James J H Chong, Freda H Passam, Beng H Chong

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
257citing papers in PubMed, 2 pooled it
50.8field-weighted citation impact, top 1% 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

257 citing papers in PubMed, 2 syntheses or guidelines pooled it, 407 citations in OpenAlex.

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  15. Inhibition of IP6K1 suppresses NPA formation via platelet short-chain polyphosphate polymers in necrotizing enterocolitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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197 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

José PerdomoHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Halina H L LeungHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Zohra AhmadiHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Feng YanHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
James J H ChongSydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Freda H PassamHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Beng H ChongHaematology Research Unit, St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. beng.chong@unsw.edu.au.
UNSW Sydney · AUSutherland Hospital · AUWestmead Institute for Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heparin-induced thrombocytopenia/thrombosis (HIT) is a serious immune reaction to heparins, characterized by thrombocytopenia and often severe thrombosis with high morbidity and mortality. HIT is mediated by IgG antibodies against heparin/platelet factor 4 antigenic complexes. These complexes are thought to activate platelets leading to thrombocytopenia and thrombosis. Here we show that HIT immune complexes induce NETosis via interaction with FcγRIIa on neutrophils and through neutrophil-platelet association. HIT immune complexes induce formation of thrombi containing neutrophils, extracellular DNA, citrullinated histone H3 and platelets in a microfluidics system and in vivo, while neutrophil depletion abolishes thrombus formation. Absence of PAD4 or PAD4 inhibition with GSK484 abrogates thrombus formation but not thrombocytopenia, suggesting they are induced by separate mechanisms. NETs markers and neutrophils undergoing NETosis are present in HIT patients. Our findings demonstrating the involvement of NETosis in thrombosis will modify the current concept of HIT pathogenesis and may lead to new therapeutic strategies.

Indexed as

AnimalsAntigen-Antibody ComplexBlood PlateletsCitrullinationEnzyme InhibitorsExtracellular TrapsGene Expression RegulationHeparinHistonesHumansImmunoglobulin GMiceMice, TransgenicMicrofluidic Analytical TechniquesNeutrophil ActivationNeutrophilsAntigen-Antibody ComplexEnzyme InhibitorsFc gamma receptor IIAHeparinHistonesImmunoglobulin GPADI4 protein, humanpeptidylarginine deiminase 4, mousePF4 protein, humanPlatelet Factor 4Protein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Receptors, IgG

Identifiers

PMID30899022
PMCPMC6428879
OpenAlexW2923462844

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.