ArticleBlood advances2016
Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia.
Article in Blood advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Modeling the role of platelet-released polyphosphates in tissue factor-initiated coagulation under flow.Research and practice in thrombosis and haemostasis · 2026Article
- Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder.bioRxiv : the preprint server for biology · 2025Article
- Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes.bioRxiv : the preprint server for biology · 2025Article
- Article
- Prothrombotic antibodies targeting the spike protein's receptor-binding domain in severe COVID-19.Blood · 2025Article
- Autoimmune Heparin-Induced Thrombocytopenia.Journal of clinical medicine · 2023Review
- Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)-Insights from Clinical Cases, In Vitro Studies and Murine Models.Journal of clinical medicine · 2023Review
- Laboratory Testing for Heparin-Induced Thrombocytopenia and Vaccine-Induced Immune Thrombotic Thrombocytopenia Antibodies: A Narrative Review.Seminars in thrombosis and hemostasis · 2023Review
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- Article
- The levels of TGFβ1, VEGF, PDGF-BB, and PF4 in platelet-rich plasma of professional soccer players: a cross-sectional pilot study.Journal of orthopaedic surgery and research · 2022Article
- Article
- Measurement of procoagulant platelets provides mechanistic insight and diagnostic potential in heparin-induced thrombocytopenia.Journal of thrombosis and haemostasis : JTH · 2022Article
- Effects of SARS-CoV-2 mRNA vaccines on platelet polyphosphate levels and inflammation: A pilot study.Biomedical reports · 2022Article
- The aetiopathogenesis of vaccine-induced immune thrombotic thrombocytopenia.Clinical medicine (London, England) · 2022Review
- The COVID-19 vaccine ChAdOx1-S is not contaminated with sulfated glycosaminoglycans.Journal of thrombosis and haemostasis : JTH · 2022Article
- Proposed mechanism for rare thrombotic events after use of some Covid-19 vaccines.Medical hypotheses · 2022Article
- Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review.Annals of medicine and surgery (2012) · 2022Review
- Polyphosphate in Antiviral Protection: A Polyanionic Inorganic Polymer in the Fight Against Coronavirus SARS-CoV-2 Infection.Progress in molecular and subcellular biology · 2022Article
- SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia.Thrombosis research · 2022Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin is cleared and platelet activation leading to release of PF4 has dissipated. We asked whether antigenic complexes between polyphosphates and PF4 released from activated platelets might intensify or sustain the prothrombotic phenotype of HIT. PF4 forms stable, ultralarge complexes with polyphosphates of various sizes, including those released from platelets, which are recognized by the HIT-like monoclonal KKO, an immunoglobulin G2bκ monoclonal heparin/PF4 binding antibody, and by human HIT antibodies. KKO helps to protect PF4/polyphosphate complexes from degradation by phosphatases. Complement is activated when HIT antibodies bind to PF4/polyphosphate complexes and PF4 reverses the inhibition of complement by polyphosphates. Polyphosphates and PF4 are stored primarily in separate granules in resting platelets, but they colocalize when the cells are activated. Platelets activated by subaggregating doses of thrombin receptor activating peptide release polyphosphates and PF4, which form antigenic complexes that allow KKO to further activate platelets in the absence of heparin and exogenous PF4. These studies suggest that thrombin- or immune complex-mediated release of endogenous antigenic PF4/polyphosphate complexes from platelets may augment the prothrombotic risk of HIT and perpetuate the risk of thrombosis after heparin has been discontinued.
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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.