PB0530 - Characterization of disseminated intravascular coagulation (DIC) in a murine model of fecal-induced peritonitis

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Neha Sharma, B.Sc and MS

Graduate student
McMaster University - The Thrombosis & Atherosclerosis Research Institute
Toronto, Ontario, Canada

Co-Author(s)

DD

Dhruva Dwivedi

Research Associate
McMaster University - The Thrombosis & Atherosclerosis Research Institute
Hamilton, Ontario, Canada
EC

Erblin Cani

Graduate student
McMaster University - The Thrombosis & Atherosclerosis Research Institute
Vaughan, Ontario, Canada
ML

Manoj Lalu

Staff Anesthesiologist, Associate Scientist, Assistant Professor
The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa
Ottawa, Ontario, Canada
AM

Asher Mendelson

Assistant Professor
University of Manitoba
Winnipeg, Manitoba, Canada
BM

Braedon McDonald

Intensivist, Assistant Professor
Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary
Calgary, Alberta, Canada
PL

Patricia Liaw, PhD

Professor, Principal Investigator
McMaster University - The Thrombosis & Atherosclerosis Research Institute
Hamilton, Ontario, Canada

Background: DIC is an acquired condition characterized by widespread intravascular coagulation that complicates many conditions including sepsis. The presence of DIC is an independent and strong predictor of organ dysfunction and mortality. For DIC diagnosis, the ISTH DIC scoring system uses platelet counts, the prothrombin time, D-dimer, and fibrinogen. However, mouse models of DIC have not been developed in a standardized way which limits comparison between models and reduces translatability. One model of murine sepsis is the fecal-induced peritonitis (FIP) model which does not require surgery and is easier to reproduce in a multi-centre setting.

Aims: To characterize the time course of DIC in a murine model of sepsis and to investigate the correlation between DIC onset and immunothrombosis.

Methods: Male and female C57Bl/6 mice (10-12 weeks old) received i.p. injections of 0.75mg/g rat fecal slurry or 5% dextrose (controls). The mice were monitored every 4h for temperature and the Murine Sepsis Score. The mice were culled at 4h, 8h, 12h, and 24 h to assess changes in the DIC score. Blood and organs were harvested and plasma markers of immunothrombosis were quantified.

Results: Injection of 0.75 mg/g of fecal slurry resulted in 60% mortality at 72 hours, a finding we previously determined as members of the National Preclinical Sepsis Platform. In the current study, measurements of the components of the DIC score revealed that the onset of DIC occurs around 8 hours post-FIP induction. The onset of DIC also correlates with elevations in markers of immunothrombosis including IL-6, thrombin-antithrombin complexes, myeloperoxidase, and extracellular DNA.

Conclusion(s): The onset of DIC occurs around 8 hours post-FIP and correlates with elevations in markers of immunothrombosis. A standardized model for sepsis-induced DIC will be useful to investigate the pathophysiology of DIC as well as to guide the optimal timing of novel therapies.