@article{Toufik Abache_Alexandre Fontayne_Dominique Grenier_Emilie Jacque_Alain Longue_Anne-Sophie Dezetter_Béatrice Souilliart_Guillaume Chevreux_Damien Bataille_Sami Chtourou_Jean-Luc Plantier_2020, place={Pavia, Italy}, title={A mutated factor X activatable by thrombin corrects bleedings in vivo in a rabbit model of antibody-induced hemophilia A}, volume={105}, url={https://haematologica.org/article/view/9558}, DOI={10.3324/haematol.2019.219865}, abstractNote={<p>Rendering coagulation factor X sensitive to thrombin was proposed as a strategy that can bypass the need for factor VIII. In this paper, this non-replacement strategy was evaluated in vitro and in vivo in its ability to correct factor VIII but also factor IX, X and XI deficiencies. A novel modified factor X, named Actiten, was generated and produced in the HEK293F cell line. The molecule possesses the required post-translational modifications, partially keeps its ability to be activated by RVV-X, factor VIIa/tissue factor, factor VIIIa/factor IXa and acquires the ability to be activated by thrombin. The potency of the molecule was evaluated in respective deficient plasmas or hemophilia A plasmas, for some with inhibitors. Actiten corrects dose dependently all the assayed deficient plasmas. It is able to normalize the thrombin generation at 20 μg/mL showing however an increased lagtime. It was then assayed in a rabbit antibody-induced model of hemophilia A where, in contrast to recombinant factor X wild-type, it normalized the bleeding time and the loss of hemoglobin. No sign of thrombogenicity was observed and the generation of activated factor X was controlled by the anticoagulation pathway in all performed coagulation assays. This data indicates that Actiten may be considered as a possible non replacement factor to treat hemophilia’s with the advantage of being a zymogen correcting bleedings only when needed.</p&gt;}, number={9}, journal={Haematologica}, author={Toufik Abache and Alexandre Fontayne and Dominique Grenier and Emilie Jacque and Alain Longue and Anne-Sophie Dezetter and Béatrice Souilliart and Guillaume Chevreux and Damien Bataille and Sami Chtourou and Jean-Luc Plantier}, year={2020}, month={Aug.}, pages={2335-2340} }