# Endothelial Dysfunction and Restoration in Trauma Induced Coagulopathy

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $2,334,771

## Abstract

Project summary/abstract:
Trauma-induced coagulopathy (TIC) is a leading driver of morbidity and mortality following severe injury.
Affecting as many as 30% of critically ill trauma patients, TIC represents a spectrum of coagulation phenotypes
ranging from early impaired hemostasis to later micro and macrovascular thrombotic complications. We have
identified that patients with TIC have evidence of severe endothelial damage, and these markers of endothelial
injury correlate closely with outcomes in trauma. Further, through randomized controlled trials testing pre-
hospital plasma as a resuscitation tool, we have identified that plasma transfusion can reduce endothelial
injury, even in the patients with the highest injury severity. Plasma transfusion reduces mortality after severe
trauma, but the exact mechanism of benefit is unknown. In the present proposal, we address the central
hypothesis that the endothelium is a central regulator of TIC. We propose to characterize the role of the
endothelium as the regulator of maladaptive response and a crucial interface for thrombosis-inflammation
crosstalk. Our strategy will focus on identifying key circulating mediators after trauma that induce endothelial
injury. We will utilize a “cue, signal, response” framework to robustly characterize the molecular pathways
activated in the endothelial and how the endothelial response interfaces with changes in the coagulation
response. Finally, we will define the “reparative phenotype” that plasma transfusion creates, restoring the
endothelium to homeostasis. We will use this to test targeted therapies to address the unmet needs in trauma
resuscitation targeting endothelial health. The approach will leverage state-of-the-science and novel
techniques in proteomics, transcriptomics, metabolomics, advanced microvascular imaging, and pre-clinical
models of trauma and hemorrhage in addition to a large repository of previously collected trauma patient
samples.

## Key facts

- **NIH application ID:** 10930121
- **Project number:** 5R01HL166944-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mitchell Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,334,771
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930121

## Citation

> US National Institutes of Health, RePORTER application 10930121, Endothelial Dysfunction and Restoration in Trauma Induced Coagulopathy (5R01HL166944-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10930121. Licensed CC0.

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