Journal of thrombosis and haemostasis : JTH · 2025
Intraosseous administration of lyophilized synthetic platelets renders hemostatic efficacy in rat model of traumatic hemorrhage.
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Liu Zeyu, Abdullah Abiha, Secunda Zachary A, Luc Norman F, Jackson Lauren, Traylor Baylee, Disharoon Dante, Pawlowski Christa, Sharma Riya, Sekhon Ujjal Didar Singh, Quill Emma, Spinella Philip Charles, Shea Susan M, Bruckman Michael A, Sen Gupta Anirban, Neal Matthew D
Аннотация
BACKGROUND: In traumatic hemorrhage, transfusion of donor-derived platelets improve hemostasis and survival, but their availability is often limited by supply constraints and short shelf-life. To address this, we have developed SynthoPlate (SP), a synthetic platelet nanotechnology that mimics the primary hemostatic functions of natural platelets, and have recently advanced its manufacturing into a shelf-stable, lyophilized powder for rapid aqueous-reconstitution and on-demand use.
OBJECTIVES: We aimed to evaluate the feasibility, safety, and efficacy of administering SP intraosseously in a rat model of traumatic hemorrhage, considering the critical clinical relevance of intraosseous access in prehospital and combat medicine.
METHODS: We first assessed SP's hemostatic cooperativity with rat platelets using a microfluidic assay. Next, SP was administered intraosseously in rats to evaluate safety and biodistribution. Finally, 0.5 mg/kg of SP was administered intraosseously in a rat liver laceration model to assess effects on hemodynamics, blood loss, and survival.
RESULTS: Microfluidic studies confirmed SP's hemostatic capability in platelet-depleted rat plasma. In pilot safety studies, intraosseously administered SP was well tolerated at doses up to 20 mg/kg, 40 times the proposed effective dose. In efficacy studies, rats treated with SP showed significantly reduced blood loss and improved survival compared with controls. SP-treated rats also exhibited higher mean arterial pressure postinjury, shorter durations of hypotension, and faster mean arterial pressure recovery.
CONCLUSION: This first-in-kind study demonstrates the feasibility of administering SP intraosseously to enhance hemostasis and survival in traumatic hemorrhage, supporting its potential as a rapidly deployable, shelf-stable platelet surrogate for use in emergency and austere settings.
OBJECTIVES: We aimed to evaluate the feasibility, safety, and efficacy of administering SP intraosseously in a rat model of traumatic hemorrhage, considering the critical clinical relevance of intraosseous access in prehospital and combat medicine.
METHODS: We first assessed SP's hemostatic cooperativity with rat platelets using a microfluidic assay. Next, SP was administered intraosseously in rats to evaluate safety and biodistribution. Finally, 0.5 mg/kg of SP was administered intraosseously in a rat liver laceration model to assess effects on hemodynamics, blood loss, and survival.
RESULTS: Microfluidic studies confirmed SP's hemostatic capability in platelet-depleted rat plasma. In pilot safety studies, intraosseously administered SP was well tolerated at doses up to 20 mg/kg, 40 times the proposed effective dose. In efficacy studies, rats treated with SP showed significantly reduced blood loss and improved survival compared with controls. SP-treated rats also exhibited higher mean arterial pressure postinjury, shorter durations of hypotension, and faster mean arterial pressure recovery.
CONCLUSION: This first-in-kind study demonstrates the feasibility of administering SP intraosseously to enhance hemostasis and survival in traumatic hemorrhage, supporting its potential as a rapidly deployable, shelf-stable platelet surrogate for use in emergency and austere settings.