ArticleJournal of thrombosis and haemostasis : JTH2015
The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.
Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- The pivotal role of von Willebrand factor binding to platelet αIIbβ3 in stabilizing the formation of a platelet plug at sites of injury.Haematologica · 2025Article
- The T follicular helper/T follicular helper regulatory pathway in FVIII immune responses in mice.Blood · 2025Article
- Rescue of the endogenous FVIII expression in hemophilia A mice using CRISPR-Cas9 mRNA LNPs.Molecular therapy. Nucleic acids · 2024Article
- A novel mouse model of type 2N VWD was developed by CRISPR/Cas9 gene editing and recapitulates human type 2N VWD.Blood advances · 2022Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential.Drug delivery and translational research · 2021Review
- The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression.Blood advances · 2020Article
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Induction of activated T follicular helper cells is critical for anti-FVIII inhibitor development in hemophilia A mice.Blood advances · 2019Article
- The impact of GPIbα on platelet-targeted FVIII gene therapy in hemophilia A mice with pre-existing anti-FVIII immunity.Journal of thrombosis and haemostasis : JTH · 2019Article
- 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
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOur previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors).
objectiveTo explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors.
methods2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test.
resultsOnly 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group.
conclusionVWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors.
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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.