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    Poster Networking

    Coagulation and Natural Anticoagulants

    Poster Networking Session

    PB1030 - Hemostatic Evaluation of Synthetic Platelet Nanotechnology in Rabbit Models of Dilutional Coagulopathy and Trauma

    Tuesday, June 27, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Transfusion of allogeneic platelets is routinely used in the clinic to treat bleeding complications in trauma, surgery, hematology/oncology, and congenital disorders. Clinical studies have shown that early platelet transfusion significantly improves hemostatic and survival outcomes in bleeding complications. However, clinical use of donor-derived platelet products is limited by their portability, high risk of pathogenic contamination, and short shelf-life, often rendering them unavailable in pre-hospital settings.

    Aims: We’ve developed a lyophilizable, shelf-stable synthetic platelet (SP) nanoparticle technology that mimics some of a platelet's primary hemostatic mechanisms to cover the unmet need for platelet surrogates for in-hospital and pre-hospital management of bleeding complications.

    Methods: SP was manufactured using thin film rehydration followed by extrusion and lyophilization. SP was reconstituted in water/PBS and evaluated for size, charge, and morphology via DLS and Cryo-TEM. Functional characteristics were evaluated in vitro via flow cytometry, BioFlux, and ROTEM; and in vivo in two models in New Zealand White Rabbits: kidney incision after dilutional coagulopathy, and splenic + hepatic polytrauma.

    Results: SP was reproducibly manufactured, lyophilized, and stored up to 12 months at ambient temperatures. Nanoparticle size and charge were conserved after reconstitution. Flow cytometry, microfluidic studies and ROTEM confirmed SP’s ability to bind to activated platelets, rescue platelet-coverage on injury site-mimetic surfaces, and improve clot formation, respectively. In a rabbit dilutional coagulopathy model, SP significantly reduced blood loss after kidney incision at a level similar to autologous platelet transfusion. In a rabbit polytrauma model, SP significantly reduced blood loss compared to vehicle treated rabbits. Additionally, vitals demonstrated no deviation compared to controls, and major organs showed no signs of systemic microthrombi.

    Conclusion(s): SP is a fully synthetic, lyophilizable, platelet mimicking nanotechnology with a long shelf-life (>12 months), and demonstrated the ability to significantly reduce blood loss in two clinically relevant models of traumatic hemorrhage in rabbits, while maintaining systemic safety.