# Red blood cell microparticles and lung inflammation after hemorrhage and resuscitation

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2021 · $353,100

## Abstract

Project Summary
The long term goal of our proposal is to understand the mechanisms by which transfusion of older packed
red blood cell (pRBC) units worsens patient outcomes after resuscitation from hemorrhage. Hemorrhagic
shock is the most common cause of potentially preventable death after trauma. Current resuscitation
strategies for patients with significant blood loss include the use pRBCs and fresh-frozen plasma. While
the use of pRBCs for resuscitation of the injured patient is essential for survival, transfusion of pRBC units
that have aged during storage is associated with worsened clinical outcomes in patients, including
increased risk of multisystem organ failure, pneumonia, renal failure, sepsis, and death. We have
demonstrated that microparticles from aged pRBC units contain red blood cell microparticles that mediate
inflammatory events after transfusion. Our previous studies and preliminary data strongly indicate that
microparticle formation is a key event during pRBC storage and that pRBC microparticles are critical
mediators of lung inflammation after resuscitation from hemorrhage. In the current proposal, we hypothesize
that microparticles from stored packed red blood cells are acutely pro-inflammatory in nature and promote
inflammatory consequences, such as endothelial cell activation, formation of pulmonary microthrombi, and
development of lung inflammation after resuscitation from hemorrhage. To test this hypothesis, we propose
the following specific aims: Aim 1: Test mechanistic strategies to reduce pRBC microparticle generation
during storage and mitigate pro-inflammatory potential of stored pRBC units; Aim 2: Determine the
molecular mechanisms of endothelial cell activation by microparticles from stored pRBC units; Aim 3:
Determine the mechanisms by which pRBC microparticles promote multi-cellular interactions leading
pulmonary microthrombi after hemorrhage and resuscitation. The proposed studies will general novel data
concerning the role of microparticles from stored pRBC units and the development of endothelial cell
dysfunction after hemorrhage and resuscitation. If successful, these studies will identify new therapeutic
targets allowing improved clinical outcomes after hemorrhage and resuscitation with stored pRBC units.

## Key facts

- **NIH application ID:** 10135988
- **Project number:** 5R01GM107625-08
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** TIMOTHY A PRITTS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $353,100
- **Award type:** 5
- **Project period:** 2014-02-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135988

## Citation

> US National Institutes of Health, RePORTER application 10135988, Red blood cell microparticles and lung inflammation after hemorrhage and resuscitation (5R01GM107625-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135988. Licensed CC0.

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