ArticleBlood2021
Complement mediates binding and procoagulant effects of ultralarge HIT immune complexes.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- On a quest for fingerprints of crystalglobulinemia on platelets and endothelium.Blood vessels, thrombosis & hemostasis · 2026Article
- Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): An Immunopathogenic Model of Dysregulated Vaccine-Triggered Immunity.Vaccines · 2026Review
- Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.Clinical and experimental medicine · 2026Review
- Methods to Examine Complement Activation by HIT Immune Complexes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder.bioRxiv : the preprint server for biology · 2025Article
- Endothelial cell activation enhances thromboinflammation in vaccine-induced immune thrombotic thrombocytopenia.Blood advances · 2025Article
- Complement activation as a biomarker for platelet-activating antibodies in heparin-induced thrombocytopenia.Journal of thrombosis and haemostasis : JTH · 2025Article
- Advances in our understanding of anti-PF4 related immunothrombosis.Frontiers in immunology · 2025Review
- The Role of Sterile Inflammation in Thrombosis: Consequences for Cardiovascular Disease and COVID-19.Mediators of inflammation · 2025Review
- Coagulation and platelet biology at the intersection of health and disease: illustrated capsules of the 11th Symposium on Hemostasis at the University of North Carolina.Research and practice in thrombosis and haemostasis · 2024Article
- Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Thrombotic anti-PF4 immune disorders: HIT, VITT, and beyond.Hematology. American Society of Hematology. Education Program · 2023Article
- Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia.Haematologica · 2023Article
- Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?Blood advances · 2023Article
- Heparin-induced thrombocytopenia: An illustrated review.Research and practice in thrombosis and haemostasis · 2023Article
- Article
- Minimal role for the alternative pathway in complement activation by HIT immune complexes.Journal of thrombosis and haemostasis : JTH · 2022Article
- Platelets get particular.Blood · 2022Article
- Live imaging of platelets and neutrophils during antibody-mediated neurovascular thrombosis.Blood advances · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing immunoglobulin G (IgG) antibodies to a multivalent antigen composed of platelet factor 4 and heparin. The limitations of current antithrombotic therapy in HIT supports the need to identify additional pathways that may be targets for therapy. Activation of FcγRIIA by HIT ULICs initiates diverse procoagulant cellular effector functions. HIT ULICs are also known to activate complement, but the contribution of this pathway to the pathogenesis of HIT has not been studied in detail. We observed that HIT ULICs physically interact with C1q in buffer and plasma, activate complement via the classical pathway, promote codeposition of IgG and C3 complement fragments (C3c) on neutrophil and monocyte cell surfaces. Complement activation by ULICs, in turn, facilitates FcγR-independent monocyte tissue factor expression, enhances IgG binding to the cell surface FcγRs, and promotes platelet adhesion to injured endothelium. Inhibition of the proximal, but not terminal, steps in the complement pathway abrogates monocyte tissue factor expression by HIT ULICs. Together, these studies suggest a major role for complement activation in regulating Fc-dependent effector functions of HIT ULICs, identify potential non-anticoagulant targets for therapy, and provide insights into the broader roles of complement in immune complex-mediated thrombotic disorders.
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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.