ArticleJournal of thrombosis and haemostasis : JTH2012
Factor VIII inhibitors: von Willebrand factor makes a difference in vitro and in vivo.
Article in Journal of thrombosis and haemostasis : JTH, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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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
12 citing papers in PubMed, 27 citations in OpenAlex.
- Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner.Frontiers in immunology · 2023Article
- Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro.International journal of molecular sciences · 2022Article
- Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential.Drug delivery and translational research · 2021Review
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Platelet-Targeted Gene Therapy for Hemophilia.Molecular therapy. Methods & clinical development · 2018Review
- The impact of von Willebrand factor on factor VIII memory immune responses.Blood advances · 2017Article
- The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.Journal of thrombosis and haemostasis : JTH · 2015Article
- Alloantibodies to therapeutic factor VIII in hemophilia A: the role of von Willebrand factor in regulating factor VIII immunogenicity.Haematologica · 2015Review
- Native plasma-derived FVIII/VWF complex has lower sensitivity to FVIII inhibitors than the combination of isolated FVIII and VWF proteins. Impact on Bethesda assay titration of FVIII inhibitors.Haemophilia : the official journal of the World Federation of Hemophilia · 2014Article
- Article
- On the versatility of von Willebrand factor.Mediterranean journal of hematology and infectious diseases · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe important association between von Willebrand factor (VWF) and factor VIII (FVIII) has been investigated for decades, but the effect of VWF on the reactivity of FVIII inhibitory antibodies, referred to as inhibitors, is still controversial.
objectiveTo investigate the interaction among VWF, FVIII and FVIII inhibitory antibodies.
methodsThree sources of inhibitors were used for in vitro studies, including the plasma from immunized VWF(null) FVIII(null) mice, purified plasma IgG from human inhibitor patients, or human monoclonal antibody from inhibitor patients' B-cell clones. Inhibitors were incubated with recombinant human FVIII (rhFVIII) either with or without VWF. The remaining FVIII activity was determined by chromogenic assay and inhibitor titers were determined. For in vivo studies, inhibitors and rhFVIII were infused into FVIII(null) or VWF(null) FVIII(null) mice followed by a tail clip survival test.
resultsVWF has a dose-dependent protective effect on FVIII, limiting inhibitor inactivation of FVIII in both mouse and human samples. A preformed complex of VWF with FVIII provides more effective protection from inhibitors than competitive binding of antibodies and VWF to FVIII. The protective effect of VWF against FVIII inactivation by inhibitors was further confirmed in vivo by infusing inhibitors and FVIII into FVIII(null) or VWF(null) FVIII(null) mice followed by a tail clip survival test.
conclusionOur results demonstrate that VWF exerts a protective effect, reducing inhibitor inactivation of FVIII, both in vitro and in vivo.
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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.