Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Marjory B. Brooks, James R. Turk, Abraham Guerrero, Padma K. Narayanan, John P. Nolan, Elizabeth G. Besteman, Dennis W. Wilson, Roberta A. Thomas, Cindy E. Fishman, Karol L. Thompson, Heidrun Ellinger-Ziegelbauer, Jennifer B. Pierson, April Paulman, Alan Y. Chiang, Albert E. Schultze
  • Journal Name : PLOS One
Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions. Available open access here.
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