# Coagulation and Complement Activation in Sepsis

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $421,095

## Abstract

PROJECT SUMMARY
Severe sepsis leads to systemic inflammation, wherein activation of the complement and coagulation systems
play critical roles. Evidence from patients and animal models suggest that sepsis is a multi-stage, multi-
factorial disease in which the early fulminate inflammatory response to the invading bacteria leads to hypo-
perfusion and ischemia reperfusion (IR) injury that evolves to multiple organ failure (MOF) and ultimately to
death.
The objectives of this proposal are to investigate if the crosstalk between the coagulation and complement
activation pathways during sepsis caused by two most common pathogens, Escherichia coli and
Staphylococcus aureus contribute to microthrombosis, vascular dysfunction, organ failure and death; and,
whether inhibition of complement activation at the C5 level could prevent MOF and improve the outcome of
sepsis.
We will use clinically relevant models of sepsis to address the following objectives: (i) determine the role of
complement activation during the bacteremic stage of E. coli sepsis and characterize the protective effects of
early treatments with C5 inhibitors; (ii) determine the effect of complement activation on platelet clearance in
sepsis; (iii) determine if delayed treatment with C5 inhibitors provides organ protection and survival benefit in a
model of sepsis-induced progressive organ failure.
Successful completion of these aims will determine: (i) whether timed complement inhibition at the C5 level
could be used as an effective therapy for sepsis-induced MOF; (ii) if deposition of complement fragments on
platelets contribute to their removal from circulation; (iii) which is the optimum therapeutic time window for
complement inhibition to attenuate the disease progression without affecting bacteria clearance.
Altogether, our project will combine basic and preclinical research to verify novel hypotheses on the
pathophysiology of Gram-negative and Gram-positive sepsis and test innovative approaches, which, in the
long-term may save lives from a deadly disease with no specific cure.
!

## Key facts

- **NIH application ID:** 9932389
- **Project number:** 5R01GM121601-04
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** FLOREA LUPU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $421,095
- **Award type:** 5
- **Project period:** 2017-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932389

## Citation

> US National Institutes of Health, RePORTER application 9932389, Coagulation and Complement Activation in Sepsis (5R01GM121601-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9932389. Licensed CC0.

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