ArticleJCI insight2018
Neutrophil accumulation and NET release contribute to thrombosis in HIT.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19.PLoS pathogens · 2021Trial
- Monovalent Anti-FcγRIIA Antibody Blocks Immune-Mediated Thrombocytopenia and Thrombosis With Minimal Adverse Side Effects in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Review
- Peripheral Blood Neutrophil-to-Lymphocyte Ratio Combined With Fibrinogen-to-Albumin Ratio Assists in Identifying Systemic Lupus Erythematosus Activity and Lupus Nephritis.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026Article
- Neutrophil extracellular traps in thrombosis of hematologic malignancies: Underlying mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Neutrophil extracellular traps-associated candidate genes in IgA vasculitis: an exploratory multi-omics analysis integrating transcriptomics and Mendelian randomization.Pediatric rheumatology online journal · 2026Article
- Host Defense Antimicrobial Peptides (HDPs) as Regulators of Hemostasis and Vascular Biology.Biomolecules · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Autophagy, NET formation, and inflammation crosstalk in thrombotic autoimmune diseases.Frontiers in immunology · 2026Review
- Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder.bioRxiv : the preprint server for biology · 2025Article
- Neutrophil Extracellular Traps (NETs) as a Potential Target for Anti-Aging: Role of Therapeutic Apheresis.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2025Review
- Plasma proteomics uncovers divergent molecular signatures in ischemic stroke and intracerebral hemorrhage.Biomarker research · 2025Article
- Proteomic insights into platelet dysregulation and pathogenic mechanisms of chronic thromboembolic pulmonary hypertension.Journal of translational medicine · 2025Article
- Anti-PF4 disorders: Pathogenesis, diagnosis and treatment.British journal of haematology · 2025Review
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- Article
- Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome.Acta biochimica et biophysica Sinica · 2025Article
- Diagnostic biomarkers and immune infiltration profiles common to COVID-19, acute myocardial infarction and acute ischaemic stroke using bioinformatics methods and machine learning.BMC neurology · 2025Article
- Structural and functional changes underlying activation of monocytes in heparin-induced thrombocytopenia.Journal of thrombosis and haemostasis : JTH · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic disorder associated with a severe prothrombotic state. We investigated whether neutrophils and neutrophil extracellular traps (NETs) contribute to the development of thrombosis in HIT. Using an endothelialized microfluidic system and a murine passive immunization model, we show that HIT induction leads to increased neutrophil adherence to venous endothelium. In HIT mice, endothelial adherence is enhanced immediately downstream of nascent venous thrombi, after which neutrophils undergo retrograde migration via a CXCR2-dependent mechanism to accumulate into the thrombi. Using a microfluidic system, we found that PF4 binds to NETs, leading them to become compact and DNase resistant. PF4-NET complexes selectively bind HIT antibodies, which further protect them from nuclease digestion. In HIT mice, inhibition of NET formation through Padi4 gene disruption or DNase treatment limited venous thrombus size. PAD4 inactivation did affect arterial thrombi or severity of thrombocytopenia in HIT. Thus, neutrophil activation contributes to the development of venous thrombosis in HIT by enhancing neutrophil-endothelial adhesion and neutrophil clot infiltration, where incorporated PF4-NET-HIT antibody complexes lead to thrombosis propagation. Inhibition of neutrophil endothelial adhesion, prevention of neutrophil chemokine-dependent recruitment of neutrophils to thrombi, or suppression of NET release should be explored as strategies to prevent venous thrombosis in HIT.
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What OpenQuestion holds
Registered trials
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.