Intravenous administration of synthetic platelets (SynthoPlateTM) in a mouse liver injury model of uncontrolled hemorrhage improves hemostasis

AbstractBackgroundClinical resuscitative treatment of traumatic hemorrhage involves transfusion of RBC, platelets and plasma in controlled ratios. However, use of such blood components, especially platelets, present many challenges including availability, portability, contamination risks, and short shelf-life, which limit the use of platelet transfusions outside of large trauma centers such as remote civilian hospitals and austere pre-hospital settings. This has prompted significant research in platelet substitutes that may resolve the above issues while providing platelet-mimetic hemostatic action. In this framework, we have developed a synthetic platelet surrogate, SynthoPlateTM, by integrative decoration of platelet function mimetic peptides on a biocompatible lipid nanovesicle platform. We have previously demonstrated hemostatic capability of SynthoPlateTM in correcting tail-bleeding time in thrombocytopenic mice. Building on this, we hypothesized that SynthoPlateTM transfusion would decrease bleeding in a murine model of acute hemorrhagic shock.MethodsA validated model of uncontrolled intraperitoneal hemorrhage, via liver laceration was utilized to induce hemorrhagic shock in mice. SynthoPlateTM, control (unmodified) particles, and normal saline were administered as pre-treatment and recue infusions to mice undergoing liver laceration and evaluated for hemostatic benefit by determining differences in blood loss and monitoring real-time hemodynamic data.ResultsPre-treatment SynthoPlateTM transfusion resulted in significant reduction of blood loss following hemorrhage, compared to control particles or normal saline treatment (0.86±0.16g CP vs. 0.84±0.13g NS vs. 0.68±0.09g SynthoPlateTM, p

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