ArticleBlood2009
A role for thrombin in the initiation of the immune response to therapeutic factor VIII.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 49 citations in OpenAlex.
- Characterization of a mouse model to study mechanisms of hemophilia A pain.Blood advances · 2026Article
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- The Crossroads of the Coagulation System and the Immune System: Interactions and Connections.International journal of molecular sciences · 2023Review
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- Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1.Frontiers in immunology · 2020Review
- Pathogenic immune response to therapeutic factor VIII: exacerbated response or failed induction of tolerance?Haematologica · 2019Review
- Factor VIII: Perspectives on Immunogenicity and Tolerogenic Strategies.Frontiers in immunology · 2019Review
- Tolerating Factor VIII: Recent Progress.Frontiers in immunology · 2019Review
- N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.Haematologica · 2018Article
- Complement C3 is a novel modulator of the anti-factor VIII immune response.Haematologica · 2018Article
- Development of inhibitory antibodies to therapeutic factor VIII in severe hemophilia A is associated with microsatellite polymorphisms in the HMOX1 promoter.Haematologica · 2013Article
- Article
- Article
- Effect of HLA DR epitope de-immunization of Factor VIII in vitro and in vivo.Clinical immunology (Orlando, Fla.) · 2012Article
- Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation.British journal of haematology · 2012Review
- Downregulation of CD40 signal and induction of TGF-β by phosphatidylinositol mediates reduction in immunogenicity against recombinant human Factor VIII.Journal of pharmaceutical sciences · 2012Article
- Phospholipid binding lowers immunogenicity of human recombinant factor VIII in von Willebrand factor knockout mice.Thrombosis and haemostasis · 2011Article
- Article
- Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral immune response in factor VIII-deficient mice.Immunology · 2010Article
- The long term immunological response of swine after two exposures to a salmon thrombin and fibrinogen hemostatic bandage.Biologicals : journal of the International Association of Biological Standardization · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Administration of human factor VIII (FVIII) to FVIII knockout hemophilia mice is a useful small animal model to study the physiologic response in patients iatrogenically immunized to this therapeutic protein. These mice manifest a robust, T cell-dependent, antibody response to exogenous FVIII treatment, even when encountered through traditionally tolerogenic routes. Thus, FVIII given via these routes elicits both T- and B-cell responses, whereas a control, foreign protein, such as ovalbumin (OVA), is poorly immunogenic. When FVIII is heat inactivated, it loses function and much of its immunogenicity. This suggests that FVIII's immunogenicity is principally tied to its function and not its structure. If mice are treated with the anticoagulant warfarin, which depletes other coagulation factors including thrombin, there is a reduced immune response to FVIII. Furthermore, when mice are treated with the direct thrombin inhibitor, hirudin, the T-cell responses and the serum anti-FVIII antibody concentrations are again significantly reduced. Notably, when FVIII is mixed with OVA, it acts to increase the immune response to OVA. Finally, administration of thrombin with OVA is sufficient to induce immune responses to OVA. Overall, these data support the hypothesis that formation of thrombin through the procoagulant activity of FVIII is necessary to induce costimulation for the immune response to FVIII treatment.
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.