ArticleBlood2014
A von Willebrand factor fragment containing the D'D3 domains is sufficient to stabilize coagulation factor VIII in mice.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Trial
- Dysregulation of the Heparanase/TFPI-2/Heparan Sulfate Axis in Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Article
- Treatment of von Willebrand disease.Blood advances · 2026Review
- Landscape and Spectrum of VWF Variants in Type 2 Von Willebrand Disease: Insights from a German Patient Cohort.Thrombosis and haemostasis · 2026Article
- Structure and multiple functions of von Willebrand factor.Haematologica · 2026Review
- Correction of VWF multimerization in type 2A/IIC von Willebrand disease by exogenous VWF propeptide supplementation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Freeze-dried plasma: Hemostasis and biophysical analyses for damage control resuscitation.Transfusion · 2025Article
- Efanesoctocog alfa: the renaissance of Factor VIII replacement therapy.Haematologica · 2024Review
- The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen.International journal of molecular sciences · 2024Review
- Article
- Targeting collagen in tumor extracellular matrix as a novel targeted strategy in cancer immunotherapy.Frontiers in oncology · 2023Review
- Endothelial VWF is critical for the pathogenesis of vaso-occlusive episode in a mouse model of sickle cell disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Efanesoctocog alfa elicits functional clot formation that is indistinguishable to that of recombinant factor VIII.Journal of thrombosis and haemostasis : JTH · 2022Article
- Phage display broadly identifies inhibitor-reactive regions in von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2021Article
- Recombinant VWF fragments improve bioavailability of subcutaneous factor VIII in hemophilia A mice.Blood · 2021Article
- Molecular coevolution of coagulation factor VIII and von Willebrand factor.Blood advances · 2021Article
- Von Willebrand Factor Facilitates Intravascular Dissemination of MicrosporidiaFrontiers in cellular and infection microbiology · 2021Article
- Recent Advances in the Treatment of Hemophilia: A Review.Biologics : targets & therapy · 2021Review
- Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2020Article
- D' domain region Arg782-Cys799 of von Willebrand factor contributes to factor VIII binding.Haematologica · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Plasma factor VIII (FVIII) and von Willebrand factor (VWF) circulate together as a complex. We identify VWF fragments sufficient for FVIII stabilization in vivo and show that hepatic expression of the VWF D'D3 domains (S764-P1247), either as a monomer or a dimer, is sufficient to raise FVIII levels in Vwf(-/-) mice from a baseline of ∼5% to 10%, to ∼50% to 100%. These results demonstrate that a fragment containing only ∼20% of the VWF sequence is sufficient to support FVIII stability in vivo. Expression of the VWF D'D3 fragment fused at its C terminus to the Fc segment of immunoglobulin G1 results in markedly enhanced survival in the circulation (t1/2 > 7 days), concomitant with elevated plasma FVIII levels (>25% at 7 days) in Vwf(-/-) mice. Although the VWF D'D3-Fc chimera also exhibits markedly prolonged survival when transfused into FVIII-deficient mice, the cotransfused FVIII is rapidly cleared. Kinetic binding studies show that VWF propeptide processing of VWF D'D3 fragments is required for optimal FVIII affinity. The reduced affinity of VWF D'D3 and VWF D'D3-Fc for FVIII suggests that the shortened FVIII survival in FVIII-deficient mice transfused with FVIII and VWF D'D3/D'D3-Fc is due to ineffective competition of these fragments with endogenous VWF for FVIII binding.
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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.