# The Therapeutic Potential of Cold Stored Platelets in Regulating Vascular Instability in Trauma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $403,750

## Abstract

PROJECT SUMMARY/ABSTRACT Administrative Supplement
The Therapeutic Potential of Cold Stored Platelets in Regulating Vascular Stability in Trauma
Trauma is the leading cause of death world-wide in individuals between the ages of 1-44, with traumatic brain
injury (TBI) being the number one cause of death after trauma. Platelet transfusion and balanced ratios of blood
products have been shown to increase survival in severely injured bleeding trauma patients. In the current US
blood-banking practice, platelets (Plts) are stored in incubators at 22°C for up to 5 days. Storage of Plts at 22°C
for 5 days is associated with a storage lesion, increased infectious risk, and an overall decline in hemostatic
function. 4°C storage of Plts has been proposed as an equivalent and in some cases superior alternative to 22
°C storage. Therapeutically, in addition to their critical role in hemostasis, Plts are known to safeguard the
integrity of the vascular endothelium. Vascular instability is a hallmark effect of traumatic injury leading
to vascular permeability, inflammation, coagulation disturbances and end organ failure. In TBI, intracranial
hemorrhage (ICH) and cerebral edema are the leading causes of mortality, which are potentially addressable by
Plt transfusion. Our previous data demonstrate that 4°C Plts regulate vascular stability and inhibit endothelial
cell (EC) permeability similar to 22°C Plts. In our original RO1 we investigated the use of 4°C Plts as a first line
therapeutic intervention in TBI to decrease cerebral edema, ICH, neuroinflammation and improve outcomes
in TBI utilizing a murine model of injury. In these studies, we found that 4°C Plts could attenuate ICH, cerebral
edema and neuroinflammation induced by TBI. We also found that 4°C Plts had equivalent clot forming potential
to 22°C Plts in injured vasculature.
 In this administrative supplement, we aim to also investigate the therapeutic effects of 4°C Plts on long-
term neurocognitive endpoints. Patients who survive moderate to severe TBI will often present with learning and
memory dysfunction weeks to years later after the TBI. We hypothesize that the beneficial effects we have
found of platelet treatment on the brain’s vasculature, will lead to benefits in neurocognitive function in TBI. In
Aim 1 we will test the efficacy of 4°C cold stored platelets in improving neurocognitive function after TBI.
We will utilize two main tests: the contextual fear conditioning test and the Morris Water Maze to test context
discrimination and learning and memory in TBI mice treated with 4°C Plts. In addition, we will conduct tracking
experiments of where the platelets go long term to answer the question of whether they are still in circulation or
in the tissue 4-6 weeks post injury. Histopathological analysis has also been added to this administrative
supplement to evaluate the chronic effects of platelet treatment on TBI induced gliosis and neuroinflammation,
two pathological conditions that can linge...

## Key facts

- **NIH application ID:** 10909765
- **Project number:** 3R01HL147880-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Shibani Pati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $403,750
- **Award type:** 3
- **Project period:** 2020-08-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909765

## Citation

> US National Institutes of Health, RePORTER application 10909765, The Therapeutic Potential of Cold Stored Platelets in Regulating Vascular Instability in Trauma (3R01HL147880-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909765. Licensed CC0.

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