# 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

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. This proposal will aim to elucidate the therapeutic effects of platelets and cold stored
(4oC) platelets on vascular stability in traumatic brain injury (TBI) with the thought that platelets
can be used as a first line therapeutic intervention in TBI to decrease cerebral edema, ICH,
neuroinflammation and improve outcomes in TBI patients. Aim 1 is a mechanistic aim designed
to investigate the structural, molecular and cellular signaling effects of 4°C storage on Plts and
on Plt-endothelial cell interactions and coagulation. Inhibitors of relevant Plt and EC signaling
pathways will be utilized to tease apart what pathways are relevant to Plt effects on endothelial
permeability. Aim 2 is designed to provide a deeper understanding of the effects of 4°C Plts on
the vascular endothelium by using state of the art intravital imaging in the cremaster muscle and
brain, to visualize the effects of 4°C Plts on vascular permeability, clot formation and preservation
of the endothelial glycocalyx. Aim 3 is designed to test out our primary hypothesis that 4°C Plts
can be used to regulate vascular stability in TBI hence improving hemostasis, decreasing
neuroinflammation and neuronal cell loss. In this revised proposal we have demonstrated our
full capabilitiy to execute the proposed studies and have refined our experiments to successfully
answer the questions posed.

## Key facts

- **NIH application ID:** 10652299
- **Project number:** 5R01HL147880-04
- **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:** 5
- **Project period:** 2020-08-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652299

## Citation

> US National Institutes of Health, RePORTER application 10652299, The Therapeutic Potential of Cold Stored Platelets in Regulating Vascular Instability in Trauma (5R01HL147880-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10652299. Licensed CC0.

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