ArticleBlood2010
In vivo efficacy of platelet-delivered, high specific activity factor VIII variants.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 55 citations in OpenAlex.
- Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis.Blood advances · 2025Article
- Review
- Adeno-Associated Virus Gene Therapy for Hemophilia.Annual review of medicine · 2023Review
- Hemophilia gene therapy: ushering in a new treatment paradigm?Hematology. American Society of Hematology. Education Program · 2021Review
- Current Clinical Applications of In Vivo Gene Therapy with AAVs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Platelet-inspired therapeutics: current status, limitations, clinical implications, and future potential.Drug delivery and translational research · 2021Review
- Mouse laser injury models: variations on a theme.Platelets · 2020Review
- Mouse models of hemostasis.Platelets · 2020Review
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Infused factor VIII-expressing platelets or megakaryocytes as a novel therapeutic strategy for hemophilia A.Blood advances · 2019Article
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Tyro3, Axl, and Mertk receptors differentially participate in platelet activation and thrombus formation.Cell communication and signaling : CCS · 2018Article
- Platelet-Targeted Gene Therapy for Hemophilia.Molecular therapy. Methods & clinical development · 2018Review
- 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
- Gene therapy for immune tolerance induction in hemophilia with inhibitors.Journal of thrombosis and haemostasis : JTH · 2016Review
- Article
- α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol.The Journal of biological chemistry · 2016Article
- Assessment of Venous Thrombosis in Animal Models.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- Overexpression of factor VIII after AAV delivery is transiently associated with cellular stress in hemophilia A mice.Molecular therapy. Methods & clinical development · 2016Article
- The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis.The Journal of clinical investigation · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Ectopically expressed, human B-domainless (hB) factor 8 (F8) in platelets improves hemostasis in hemophilia A mice in several injury models. However, in both a cuticular bleeding model and a cremaster laser arteriole/venule injury model, there were limitations to platelet-derived (p) hBF8 efficacy, including increased clot embolization. We now address whether variants of F8 with enhanced activity, inactivation resistant F8 (IR8) and canine (c) BF8, would improve clotting efficacy. In both transgenic and lentiviral murine model approaches, pIR8 expressed at comparable levels to phBF8, but pcBF8 expressed at only approximately 30%. Both variants were more effective than hBF8 in cuticular bleeding and FeCl(3) carotid artery models. However, in the cremaster injury model, only pcBF8 was more effective, markedly decreasing clot embolization. Because inhibitors of F8 are stored in platelet granules and IR8 is not protected by binding to von Willebrand factor, we also tested whether pIR8 was effective in the face of inhibitors and found that pIR8 is protected from the inhibitors. In summary, pF8 variants with high specific activity are more effective in controlling bleeding, but this improved efficacy was inconsistent between bleeding models, perhaps reflecting the underlying mechanism(s) for the increased specific activity of the studied F8 variants.
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.