ArticleNature communications2016
Neutralizing blood-borne polyphosphate in vivo provides safe thromboprotection.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 74 citations in OpenAlex.
- Review
- Nuclear speckle dynamics are controlled by polyphosphate inhibition of CLK proteins.Nucleic acids research · 2026Article
- An antibody targeting high-molecular-weight kininogen blocks contact system activation in a model of polymicrobial sepsis.Journal of thrombosis and haemostasis : JTH · 2025Article
- Factor XII-driven coagulation traps bacterial infections.The Journal of experimental medicine · 2025Article
- Advancements in research on the thrombo-inflammation mechanisms mediated by factor XII in ischemic stroke.Journal of thrombosis and thrombolysis · 2025Review
- Inhibitors of Polyphosphate and Neutrophil Extracellular Traps.Seminars in thrombosis and hemostasis · 2024Review
- An Update on Polyphosphate In Vivo Activities.Biomolecules · 2024Review
- Antipolyphosphate monoclonal antibodies derived from autoimmune mice.Research and practice in thrombosis and haemostasis · 2024Article
- Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.Nature communications · 2024Article
- The Concept of Thromboinflammation.Hamostaseologie · 2024Review
- Polyphosphate-loaded silk fibroin membrane as hemostatic agent in oral surgery: a pilot study.International journal of implant dentistry · 2023Article
- Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design.Nature communications · 2023Article
- Immunothrombosis and the Role of Platelets in Venous Thromboembolic Diseases.International journal of molecular sciences · 2022Review
- Influence of Steric Shield on Biocompatibility and Antithrombotic Activity of Dendritic Polyphosphate Inhibitor.Molecular pharmaceutics · 2022Article
- Article
- Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood.Frontiers in cardiovascular medicine · 2022Article
- Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation.Blood advances · 2021Article
- Identification of the factor XII contact activation site enables sensitive coagulation diagnostics.Nature communications · 2021Article
- Fluorometric Quantification of Human Platelet Polyphosphate Using 4',6-Diamidine-2-phenylindole Dihydrochloride: Applications in the Japanese Population.International journal of molecular sciences · 2021Article
- Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate.Blood · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow. PPX and PPX_Δ12 infusions in wild-type mice interfere with arterial thrombosis and protect animals from activated platelet-induced venous thromboembolism without increasing bleeding from injury sites. In contrast, targeting polyphosphate does not provide additional protection from thrombosis in factor XII-deficient animals. Our data provide a proof-of-concept approach for combating thrombotic diseases without increased bleeding risk, indicating that polyphosphate drives thrombosis via factor XII.
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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.