Abstract
Background
Early hemostatic resuscitation with platelets can significantly improve survival in hemorhaging patients. Here, platelet-mimicking technologies can serve as surrogates when donor-derived platelets are unavailable. We have developed a synthetic platelet technology (SynthoPlate, SP) that mimics platelet's primary hemostatic mechanisms, and have previously reported its efficacy. Recently we have advanced SP into a lyophilized product (Lyo-SP) that preserves functional equivalence to SP while allowing long shelf-life, easy portability, and rapid reconstitution for on-demand use.Objective
We evaluated Lyo-SP in an emergency setting in a rat model of liver injury hemorrhage.Methods
First, Lyo-SP was tested ex vivo in two complementary microfluidic assays (BioFlux and T-TAS) to establish functionality in rat blood. Subsequently, Lyo-SP was administered in rats at escalating doses to determine safety. Finally, Lyo-SP hemostatic efficacy was evaluated in the rat liver hemorrhage model, given at two different doses at two different time-points post-injury, simulating emergency treatment.Results
Ex vivo, Lyo-SP demonstrated significant hemostatic capability in a rat blood-based hemodilution model. In vivo, Lyo-SP was well-tolerated in rats up to 20 mg/kg and showed no clotting risks in clearance organs, confirmed by histology. In the liver hemorrhage model, rats dosed with 0.5 mg/kg Lyo-SP immediately (∼1-min) or at 5-min post-injury minimally reduced blood loss and mortality compared to controls. In contrast, rats dosed with 5 mg/kg Lyo-SP immediately (∼1-min) or at 5-min post-injury significantly reduced blood loss and mortality.Conclusions
The results indicate significant promise of Lyo-SP as an on-demand therapy for emergency management of hemorrhage to improve survival.