ArticleNature communications2015
Atomic description of the immune complex involved in heparin-induced thrombocytopenia.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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.
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
78 citing papers in PubMed, 131 citations in OpenAlex.
- Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera.BioMed research international · 2017Trial
- Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2026Review
- A cryptic symmetry switch allosterically controls how the PF4 self-protein turns into a pathogenic antigen.Nature communications · 2026Article
- Thromboinflammatory and Pharmacological Effects of Low-Molecular-Weight Heparins in Acute Venous Thromboembolism: An Integrated Clinical and In Silico Analysis.Medical sciences (Basel, Switzerland) · 2026Article
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder.bioRxiv : the preprint server for biology · 2025Article
- Glycoprotein VI is a receptor for the PF4/anti-PF4 IgG complex and contributes to platelet activation in heparin-induced thrombocytopenia (HIT).Journal of thrombosis and haemostasis : JTH · 2025Article
- Investigation into the binding domains of platelet factor 4 unlocks new avenues for the design and synthesis of selective sulfated pseudo-tetrasaccharide aminoglycoside ligands.European journal of medicinal chemistry · 2025Article
- Reversible Platelet Aggregation Induced by Low-Temperature Storage in Heparinized Whole Blood Samples.Hematology reports · 2025Article
- Review
- Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.Cell · 2025Article
- Article
- Adenovirus vectors can infect mouse megakaryocytes - implications for vaccine-induced thrombosis/thrombocytopenia.Research and practice in thrombosis and haemostasis · 2025Article
- Structural and functional changes underlying activation of monocytes in heparin-induced thrombocytopenia.Journal of thrombosis and haemostasis : JTH · 2025Article
- Article
- Chemokine Oligomers and the Impact of Fondaparinux Binding.Journal of the American Society for Mass Spectrometry · 2024Article
- Molecular architecture and platelet-activating properties of small immune complexes assembled on heparin and platelet factor 4.Communications biology · 2024Article
- Transient Autoreactive PF4 and Antiphospholipid Antibodies in COVID-19 Vaccine Recipients.Vaccines · 2023Article
- Reverse Engineering of a Pathogenic Antibody Reveals the Molecular Mechanism of Vaccine-Induced Immune Thrombotic Thrombocytopenia.Journal of the American Chemical Society · 2023Article
- Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.Biomolecules · 2023Article
18 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
11 authors at 4 institutions in 1 country.
Funding
Abstract
Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the 'open' end of the tetramer. Fondaparinux and KKO thereby collaborate to 'stabilize' the ternary pathogenic immune complex. Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. The atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.
Indexed as
Identifiers
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.