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SPLTRAK Abstract Submission
Antihemophilic Factor (Human) characterization: focus on TTP treatment
Benedetta Bonito1, Cristina Genuardo1,2, Ilaria Nardini1, Andrea Caricasole1, Claudio Farina1, Novinyo S. Amega3, Filippo Mori1
1Department of Research & Innovation, Kedrion SpA, Via di Fondovalle, Loc. Bolognana, Italy/2Department of Pharmacy, Pisa, Italy/3Department of Medical Affairs, Fort Lee, NJ, United States

Background: Thrombotic thrombocytopenic purpura (TTP) is an ultra-rare disease, characterized by ADAMTS13 deficiency, an enzyme responsible for the cleavage of ultra-large von Willebrand factor (VWF) multimers. TTP etiology can be genetic or mediated by an immune response toward the enzyme, and can be fatal if not appropriately addressed. Treatment usually involves the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis in order to remove anti-ADAMTS13 autoantibodies and replace functional ADAMTS13. Objectives: A plasma-derived double viral inactivated Factor VIII concentrate (Antihemophilic Factor (Human)) has been recently proposed as an alternative treatment for TTP, as it seems to contain high levels of ADAMTS13. Based on these findings, the aim of the present study was to assess protein levels and activity of ADAMTS13 and vWF, as well as the multimeric profile of VWF in Antihemophilic Factor (Human). Methods: A total of 12 lots of antihemophilic Factor (Human) were analyzed. ADAMTS13 Activity was measured, both by a chromogenic substrate assay and a fluorescence resonance energy transfer (FRET) test. VWF antigen and activity (CBA and RCo) were assessed as well by chemiluminescence assays. VWF multimeric pattern was evaluated by agarose based gel electrophoresis. Results: The results were significantly correlated and highlighted ADAMTS13 protein integrity, as inferred by an activity to antigen ratio of 0.740.32. vWF protein integrity was evidenced (vWF:CBA/vWF:Ag ratio of 0.88 0.07) and confirmed by the multimeric profile of the protein. These results are in accordance with data obtained by an independent Centre, and confirm literature reports on plasma-derived FVIII/vWF concentrate suitability for the treatment/prophylaxis of acute microangiopathy episodes in patients affected by TTP. Conclusions: Antihemophilic Factor (Human) represents a possible candidate therapy in TTP and a potential alternative to FFP because of higher ADAMTS13 levels and safer viral profile relative to FFP.