Trauma is the leading cause of death for people ages 1-44, with blood loss comprising 60-70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds including pressure dressings, tourniquets or topical materials (e.g. QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ~50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1-hour survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles’ effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.

Significance We have developed hemostatic nanoparticles that reduce bleeding and increase survival in both the short term and long term following the complex injuries sustained during blast trauma. This treatment has the potential to be deployed by first responders to save lives.

According to the CDC, the leading cause of death for both men and women between the ages of 5 and 44 is traumatic injury. Blood loss is the primary cause of death at acute time points post trauma. Early intervention is critical to save lives, and yet there are no treatments to stop internal bleeding that can be deployed in the field. In this work, we developed hemostatic nanoparticles that are stable at high temperatures (50 °C for 7 days) and are still effective at stopping bleeding and improving survival over the one hour time period in a rat liver injury model. These particles are exceptionally simple: PLA-based nanospheres functionalized with PEG terminated with variants of the RGD motif. This simple system can be stored at temperatures up to 50°C and maintain size, shape, and efficacy. The particles lead to a reduction in bleeding and increased acute survival with significance compared to both control particles and saline. Overall, these hemostatic nanoparticles offer an important step towards an immediate intervention in the field to stop bleeding and improve survival.

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