ArticleJournal of thrombosis and haemostasis : JTH2014
Improved hemostasis in hemophilia mice by means of an engineered factor Va mutant.
Article in Journal of thrombosis and haemostasis : JTH, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Maladaptive lymphangiogenesis is associated with synovial iron accumulation and delayed clearance in factor VIII-deficient mice after induced hemarthrosis.Journal of thrombosis and haemostasis : JTH · 2023Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- An engineered activated factor V for the prevention and treatment of acute traumatic coagulopathy and bleeding in mice.Blood advances · 2022Article
- Adeno-associated virus-mediated expression of activated factor V (FVa) for hemophilia phenotypic correction.Frontiers in medicine · 2022Article
- Cerebral Cavernous Malformation: From Mechanism to Therapy.Circulation research · 2021Review
- An engineered factor Va prevents bleeding induced by direct-acting oral anticoagulants by different mechanisms.Blood advances · 2020Article
- Cardiac Myosin Promotes Thrombin Generation and Coagulation In Vitro and In Vivo.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease.Seminars in hematology · 2020Review
- Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.Journal of thrombosis and haemostasis : JTH · 2019Article
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Cerebral cavernous malformations form an anticoagulant vascular domain in humans and mice.Blood · 2019Article
- Defective TAFI activation in hemophilia A mice is a major contributor to joint bleeding.Blood · 2018Article
- Novel alternate hemostatic agents for patients with inhibitors: beyond bypass therapy.Hematology. American Society of Hematology. Education Program · 2017Review
- Article
- Safety, Stability and Pharmacokinetic Properties of (super)Factor Va, a Novel Engineered Coagulation Factor V for Treatment of Severe Bleeding.Pharmaceutical research · 2016Article
- Improved coagulation and haemostasis in haemophilia with inhibitors by combinations of superFactor Va and Factor VIIa.Thrombosis and haemostasis · 2016Article
- Review
- Acquired hemophilia A: emerging treatment options.Journal of blood medicine · 2015Review
- An engineered factor Va prevents bleeding induced by anticoagulant wt activated protein C.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFactor (F)VIIa-based bypassing not always provides sufficient hemostasis in hemophilia.
objectivesTo investigate the potential of engineered activated factor V (FVa) variants as bypassing agents in hemophilia A.
methodsActivity of FVa variants was studied in vitro using prothrombinase assays with purified components and in FV- and FVIII-deficient plasma using clotting and thrombin generation assays. In vivo bleed reduction after the tail clip was studied in hemophilia A mice. RESULTS AND
conclusionsFVa mutations included a disulfide bond connecting the A2 and A3 domains and ones that rendered FVa resistant to inactivation by activated protein C (APC). '(super) FVa,' a combination of the A2-A3 disulfide (A2-SS-A3) to stabilize FVa and of APC-cleavage site mutations (Arg506/306/679Gln), had enhanced specific activity and complete APC resistance compared with wild-type FVa, FVL eiden (Arg506Gln), or FVaL eiden (A2-SS-A3). Furthermore, (super) FVa potently increased thrombin generation in vitro in FVIII-deficient plasma. In vivo, (super) FVa reduced bleeding in FVIII-deficient mice more effectively than wild-type FVa. Low-dose (super) FVa, but not wild-type FVa, decreased early blood loss during the first 10 min by more than two-fold compared with saline and provided bleed protection for the majority of mice, similar to treatments with FVIII. During the second 10 min after tail cut, (super) FVa at high dose, but not wild-type FVa, effectively reduced bleeding. These findings suggest that (super) FVa enhances not only clot formation but also clot stabilization. Thus, (super) FVa efficiently improved hemostasis in hemophilia in vitro and in vivo and may have potential therapeutic benefits as a novel bypassing agent in hemophilia.
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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.