ArticleThrombosis research2012
Effect of BAX499 aptamer on tissue factor pathway inhibitor function and thrombin generation in models of hemophilia.
Article in Thrombosis research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Challenges in the Quantification of Free TFPI in Human Plasma Following Marstacimab Treatment.The AAPS journal · 2026Article
- Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran-Results of the phase 1 inhibitor cohort.Journal of thrombosis and haemostasis : JTH · 2021Article
- Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia.International journal of hematology · 2020Review
- Novel insights into the role of aptamers in the fight against cancer.Journal of cancer research and clinical oncology · 2019Review
- Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.Blood advances · 2019Article
- The effect of the chemical chaperone 4-phenylbutyrate on secretion and activity of the p.Q160R missense variant of coagulation factor FVII.Cell & bioscience · 2019Article
- Identification of serpins specific for activated protein C using a lysate-based screening assay.Scientific reports · 2018Article
- The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2018Review
- Novel therapies and current clinical progress in hemophilia A.Therapeutic advances in hematology · 2018Review
- From selection hits to clinical leads: progress in aptamer discovery.Molecular therapy. Methods & clinical development · 2016Review
- Modulation of the Coagulation Cascade Using Aptamers.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- Correcting thrombin generation ex vivo using different haemostatic agents following cardiac surgery requiring the use of cardiopulmonary bypass.Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis · 2015Article
- Biology of tissue factor pathway inhibitor.Blood · 2014Review
- Nucleic Acid aptamers: new methods for selection, stabilization, and application in biomedical science.Biomolecules & therapeutics · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
introductionIn hemophilia, thrombin generation is significantly suppressed due to decreased factor (F)X activation. Clinical studies and experiments with transgenic mice have suggested that the severity of hemophilia is substantially reduced by tissue factor pathway inhibitor (TFPI) deficiency.
methodsWe evaluated the effect of TFPI antagonist aptamer BAX499 (formerly ARC19499) on TFPI function in purified systems and on thrombin generation and clot formation in plasma and blood.
resultsBAX499 effectively neutralized TFPI inhibition of FXa and FXa dependent inhibition of TF/FVIIa by TFPI. BAX499 did not inhibit FXa or TF/FVIIa when used up to 500 nM. In the synthetic coagulation proteome with TFPI at its mean physiologic concentration, BAX499 at 1 - 10nM increased thrombin generation triggered with 5 pM relipidated TF in a concentration-dependent manner. In severe hemophilia A or B models using the synthetic coagulation proteome, the addition of BAX499 at 5 nM increased thrombin generation to the levels observed in normal control. Thrombin generation measured in induced hemophilia B plasma required ~100nM BAX499 to restore thrombin levels to those seen in untreated plasma. In induced hemophilia B whole blood, BAX499 repaired the clotting time but failed to appreciably impact the propagation phase of thrombin generation.
conclusionThese data suggest that inhibition of TFPI by BAX499 may have potential for hemophilia treatment but requires further study in blood-based hemophilia systems.
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