1. Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma.
- Author
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Gorczyca ME, Nair SC, Jilma B, Priya S, Male C, Reitter S, Knoebl P, Gilbert JC, Schaub RG, Dockal M, McGinness KE, Pabinger I, and Srivastava A
- Subjects
- Adolescent, Adult, Aged, Austria, Blood Coagulation genetics, Case-Control Studies, Child, Child, Preschool, Dose-Response Relationship, Drug, Hemophilia A diagnosis, Hemophilia A genetics, Hemophilia B diagnosis, Hemophilia B genetics, Humans, India, Lipoproteins blood, Lipoproteins genetics, Middle Aged, Severity of Illness Index, Thrombelastography, Thrombin metabolism, Whole Blood Coagulation Time, Young Adult, Aptamers, Nucleotide pharmacology, Blood Coagulation drug effects, Hemophilia A blood, Hemophilia B blood, Hemostatics pharmacology, Lipoproteins antagonists & inhibitors, Signal Transduction drug effects
- Abstract
Background: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor-initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI., Objectives: The aim of the study was to examine the concentration-dependent augmentation of clotting by BAX499., Methods: Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet-poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N=55) and B (N=11), patients with acquired hemophilia A (N=1), and healthy controls (N=37)., Results: BAX499 significantly improved clotting of samples from hemophilic patients in a concentration-dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls., Conclusion: BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients., (© 2012 International Society on Thrombosis and Haemostasis.)
- Published
- 2012
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