Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 1;96(3):364-370.
doi: 10.1097/TA.0000000000004210. Epub 2023 Nov 27.

Pilot study of frozen platelet extracellular vesicles as a therapeutic agent in hemorrhagic shock in rats

Samantha Durbin  1 , Lindsey Loss, Lydia Buzzard, Karen Minoza, Marissa Beiling, Carmen Karsonovich, Moqing Liu, Joseph Garay, Alexander Fields, Michael Mathews, Benjamin Kuhn, Keith Moskowitz, Byron Miyazawa, Alpa Trivedi, Lucy Kornblith, Michael Fitzpatrick, Shibani Pati, Martin Schreiber
Affiliations

Pilot study of frozen platelet extracellular vesicles as a therapeutic agent in hemorrhagic shock in rats

Samantha Durbin et al. J Trauma Acute Care Surg. .

Abstract

Background: Hemorrhage accounts for the most preventable deaths after trauma. Resuscitation is guided by studies that demonstrate improved outcomes in patients receiving whole blood or balanced administration of blood products. Platelets present a logistical challenge due to short shelf life and need for refrigeration. Platelet-derived extracellular vesicles (PEVs) are a possible platelet alternative. Platelet-derived extracellular vesicles are secreted from platelets, have hemostatic effects and mitigate inflammation and vascular injury, similar to platelets. This pilot study aimed to elucidate the therapeutic effects of PEVs in a rat model of uncontrolled hemorrhage.

Methods: Male rats were anesthetized and femoral vessels cannulated. Vital signs (MAP, HR, and RR) were monitored. Electrolytes, lactate and ABG were obtained at baseline, 1-hour and 3-hours post injury. Laparotomy was performed, 50% of the middle hepatic lobe excised and the abdomen packed with gauze. Rats received 2 mL PEVs or lactated Ringers (LR) over 6 minutes immediately after injury. Peritoneal blood loss was quantified using preweighed gauze at 5 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes. Laparotomy was closed 1-hour postinjury. Animals were monitored for 3 hours postinjury then euthanized. Generalized Linear Mixed Effects models were performed to assess effects of treatment and time on lactate and MAP.

Results: Twenty-one rats were included (11 LR, 10 PEV). Overall blood loss was between 6 mL and 10 mL and not significantly different between groups. There was a 36% mortality rate in the LR group and 0% mortality in the PEV group ( p = 0.03). The LR group had significantly higher lactates at 1 hour ( p = 0.025). At 15 minutes, 45 minutes, 60 minutes, and 180 minutes, the MAP of the PEV group was significantly higher than the LR group.

Conclusion: Early studies are encouraging regarding the potential use of PEVs in uncontrolled hemorrhagic shock based on improved survival and hemodynamics.

PubMed Disclaimer

References

    1. Lopez E, Srivastava AK, Pati S, Holcomb JB, Wade CE. Platelet-derived microvesicles: a potential therapy for trauma-induced coagulopathy. Shock . 2018;49(3):243–248.
    1. Lopez E, Srivastava AK, Burchfield J, Wang YW, Cardenas JC, Togarrati PP, et al. Platelet-derived- extracellular vesicles promote hemostasis and prevent the development of hemorrhagic shock. Sci Rep . 2019;9(1):17676.
    1. Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA . 2015;313(5):471–482.
    1. Dyer MR, Alexander W, Hassoune A, Chen Q, Brzoska T, Alvikas J, et al. Platelet-derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice. J Thromb Haemost . 2019;17(10):1733–1745.
    1. Alsaadi N, Srinivasan AJ, Seshadri A, Shiel M, Neal MD, Scott MJ. The emerging therapeutic potential of extracellular vesicles in trauma. J Leukoc Biol . 2022;111(1):93–111.

LinkOut - more resources