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Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

ABSTRACT: Traumatic non-compressible hemorrhage is a leading cause of civilian and military mortality and its treatment requires massive transfusion of blood components, especially platelets. However, in austere civilian and battlefield locations, access to platelets is highly challenging due to limited supply and portability, high risk of bacterial contamination and short shelf-life. To resolve this, we have developed an I.V.-administrable 'synthetic platelet' nanoconstruct (SynthoPlate), that can mimic and amplify body's natural hemostatic mechanisms specifically at the bleeding site while maintaining systemic safety. Previously we have reported the detailed biochemical and hemostatic characterization of SynthoPlate in a non-trauma tail-bleeding model in mice. Building on this, here we sought to evaluate the hemostatic ability of SynthoPlate in emergency administration within the 'golden hour' following traumatic hemorrhagic injury in the femoral artery, in a pig model. We first characterized the storage stability and post-sterilization biofunctionality of SynthoPlate in vitro. The nanoconstructs were then I.V.-administered to pigs and their systemic safety and biodistribution were characterized. Subsequently we demonstrated that, following femoral artery injury, bolus administration of SynthoPlate could reduce blood loss, stabilize blood pressure and significantly improve survival. Our results indicate substantial promise of SynthoPlate as a viable platelet surrogate for emergency management of traumatic bleeding.

SUBMITTER: Hickman DA

PROVIDER: S-EPMC5814434 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

Hickman DaShawn A DA Pawlowski Christa L CL Shevitz Andrew A Luc Norman F NF Kim Ann A Girish Aditya A Marks Joyann J Ganjoo Simi S Huang Stephanie S Niedoba Edward E Sekhon Ujjal D S UDS Sun Michael M Dyer Mitchell M Neal Matthew D MD Kashyap Vikram S VS Sen Gupta Anirban A

Scientific reports 20180215 1

Traumatic non-compressible hemorrhage is a leading cause of civilian and military mortality and its treatment requires massive transfusion of blood components, especially platelets. However, in austere civilian and battlefield locations, access to platelets is highly challenging due to limited supply and portability, high risk of bacterial contamination and short shelf-life. To resolve this, we have developed an I.V.-administrable 'synthetic platelet' nanoconstruct (SynthoPlate), that can mimic ...[more]

PMID: 29449604

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Project description:We evaluate patients with shock and traumatic brain injury who were previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome.This was a secondary analysis of patients with shock and traumatic brain injury who were aged 15 years or older and enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 emergency medical services agencies transporting to 46 Level I and II trauma centers in 11 sites (May 2006 through May 2009). Inclusion criteria were systolic blood pressure less than or equal to 70 mm Hg or systolic blood pressure 71 to 90 mm Hg with pulse rate greater than or equal to 108 beats/min (shock cohort) and Glasgow Coma Scale score less than or equal to 8 (traumatic brain injury cohort); patients meeting both criteria were placed in the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6-month Glasgow Outcome Scale-Extended score less than or equal to 4 (traumatic brain injury cohort).There were 778 patients in the shock cohort (26% 28-day mortality) and 1,239 patients in the traumatic brain injury cohort (53% 6-month Glasgow Outcome Scale-Extended score ?4). Out-of-hospital time greater than 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.77 to 2.62) or traumatic brain injury cohort (aOR 0.77; 95% CI 0.51 to 1.15). However, shock patients requiring early critical hospital resources and arriving after 60 minutes had higher 28-day mortality (aOR 2.37; 95% CI 1.05 to 5.37); this finding was not observed among a similar traumatic brain injury subgroup.Among out-of-hospital trauma patients meeting physiologic criteria for shock and traumatic brain injury, there was no association between time and outcome. However, the subgroup of shock patients requiring early critical resources and arriving after 60 minutes had higher mortality.

Dataset Information

Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

Publications

Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

Similar Datasets

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