Background: Platelet transfusions are clinically used in thrombocytopenia, surgery, trauma etc. However, platelets have limited availability, portability, high risk of contamination, and short shelf-life (~ 5 days), which severely limit their use. Therefore, there is a significant need for an intravenous hemostat with easy manufacturability, portability and long shelf-life, that enables platelet-mimetic hemostasis when platelets are unavailable. To this end, we have developed a synthetic platelet nanotechnology.

Aims: Evaluate hemostatic efficacy of synthetic platelets.

Methods: Synthetic platelets were manufactured on a liposomal template to mimic platelet’s hemostasis-relevant adhesive and aggregatory mechanisms by decoration with VWF-binding, collagen-binding and active platelet GPIIb-IIIa-binding peptides. The particles were sterilized and stored at room temperature in suspension or lyophilized powder, and particle stability was assessed by DLS. Their platelet-mimetic bioactivity was assessed by aggregometry, microfluidics and ROTEM. The hemostasis-augmenting procoagulant and secretory mechanisms of platelet were further engineered into the particle by modifying the surface with phosphatidylserine (PS) or loading them with polyphosphate (PolyP). Their hemostatic efficacy was evaluated in vitro and in vivo.

Results: Synthetic platelets showed high stability in long-term storage as suspension or powder, and maintained platelet-mimetic bioactivity. Aggregometry showed that they could specifically enhance aggregation of active platelets but did not affect resting platelets. ROTEM studies showed that they improved clot kinetics and firmness. In vivo, they did not show systemic toxicity, immune activation or off-target thrombotic risks. Incorporation of PS or PolyP components in the synthetic platelets enabled enhanced hemostatic outputs even when natural platelets were depleted or dysfunctional. In vivo, the particles reduced blood loss, stabilized blood pressure and significantly improved survival.

Conclusions: Synthetic platelet surrogates are a promising hemostatic nanotechnology for transfusion management of bleeding dysfunctions.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/intravenous-synthetic-platelet-nanotechnology-for-the-treatment-of-bleeding-complications/