PO054 | HEMOSTASIS RESTORATION AFTER SPIKE OF FACTOR V CONCENTRATE IN COMMERCIAL FACTOR V-DEPLETED PLASMA

V. Marzano², R. Russo², E. Porfido¹, F. Pierantoni¹, C. Scali¹, A. Salvatore¹, A. Carlucci¹, M. Sotgiu¹, A. Caricasole¹, F. Taglieri¹ | ¹Kedrion S.p.A., Barga, Italy; ²Università degli Studi della Campania “Luigi Vanvitelli”, Caserta, Italy

Background and Aims. Human coagulation Factor V (FV) has a central role as a non enzymatic cofactor within the Prothrombinase Complex, where it markedly accelerates the conversion of prothrombin to thrombin. Congenital FV deficiency (Parahaemophilia) is an uncommon autosomal recessive disorder characterized by decreased functional FV levels which manifests symptoms from mild bleeding to life-threatening haemorrhages. Therapeutic options are limited to Fresh Frozen Plasma (FFP) administration, due to the lack of approved recombinant FV or plasma-derived concentrates. FFP therapy presents significant limitations, including transfusion-related adverse events and potential pathogen transmission. The present study aimed to evaluate the capacity of a novel lyophilized FV preparation to restore the haemostasis function after spike in commercial FV-depleted Plasma.
Methods. Two pilot batches (N1 and N2) were manufactured from human plasma using a multistep purification process combining chromatography and tangential flow ultrafiltration. Biochemical and functional characterization of the FV preparations obtained were performed. Purity and structural integrity were assessed by SDS-PAGE and Western blot analysis. Factor V activity was determined using a clot based functional assay based on a modified prothrombin time. The resulting lyophilized FV preparations were spiked into FV-depleted plasma (provided by Instrumentation Laboratory) at three different dilutions.
Results. Both lyophilized preparations showed FV Potency within the predefined expected range (16-24 IU/mL) of respectively 17,14 IU/mL (N1) and 17,79 IU/mL (N2). SDS-PAGE analysis showed no evidence of activation immediately after production. Three levels of spike (1:20, 1:40 and 1:80) for each preparation were performed in FV-depleted plasma. Potency assays demonstrated effective restoration of the haemostasis within the target range (0,8-1,2; 0,4-0,6; 0,2-0,3 IU/mL respectively for each level of spike).
Conclusions. These preliminary results demonstrate that both lyophilized preparations can restore the haemostasis in FV-depleted plasma. Further studies are required to evaluate long-term stability and safety.