ArticleJournal of thrombosis and haemostasis : JTH2015
Comparison of platelet-derived and plasma factor VIII efficacy using a novel native whole blood thrombin generation assay.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Impact of antiplatelet therapy on the hemostatic efficacy of platelet-targeted FVIII gene therapy in hemophilia A mice.Blood advances · 2026Article
- 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
- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells.Journal of thrombosis and haemostasis : JTH · 2023Article
- Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression.Research (Washington, D.C.) · 2023Article
- A novel mouse model of type 2N VWD was developed by CRISPR/Cas9 gene editing and recapitulates human type 2N VWD.Blood advances · 2022Article
- Intrinsic coagulation pathway-mediated thrombin generation in mouse whole blood.Frontiers in cardiovascular medicine · 2022Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Enhancing therapeutic efficacy of in vivo platelet-targeted gene therapy in hemophilia A mice.Blood advances · 2020Article
- The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression.Blood advances · 2020Article
- Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.Journal of thrombosis and haemostasis : JTH · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWe have recently developed a successful gene therapy approach for hemophilia A in which factor VIII (FVIII) expression is targeted to platelets by the αIIb promoter. Levels of platelet-expressed FVIII (2bF8) achieved by gene therapy may vary between individuals due to differences in ex vivo transduction and gene expression efficiency. Accurate assays to evaluate 2bF8 efficacy are desirable.
objectiveTo compare the hemostatic efficacy of 2bF8 with replacement therapy over a wide therapeutic dose range.
methodsEfficacy of 2bF8 was assessed using a new transgenic mouse model expressing high 2bF8 levels (LV18(tg) ). Blood from LV18(tg) mice or FVIII(null) mice infused with recombinant FVIII was mixed with FVIII(null) blood at different ratios ex vivo to achieve several concentrations of 2bF8 or plasma FVIII. Samples were evaluated with a novel native whole blood thrombin generation assay that uses recalcified whole blood without the addition of tissue factor to initiate coagulation.
resultsFVIII dose dependency was observed in all five thrombin generation parameters. While the total amount of thrombin generated was similar, 2bF8 significantly accelerated thrombin generation compared with plasma FVIII. Remarkably, a 10-fold lower dose of 2bF8 than plasma FVIII (0.2% vs. 2%) significantly shortened the onset and peak of thrombin generation compared with FVIII(null) blood.
conclusionUsing a new transgenic mouse model, we showed that the novel native whole blood thrombin generation assay established here can be used to monitor platelet targeted FVIII gene therapy. The higher therapeutic efficacy of 2bF8 compared with factor replacement therapy seemed to be due to acceleration of thrombin generation.
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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.