Hypofibrinolysis induced by tranexamic acid does not influence inflammation and mortality in a polymicrobial sepsis model

Author(s)

Campos Nogueira, Yzabella Alves ^[1] ; Gomes da Costa, Loredana Nilkenes ^{[1, 2]} ; Levy, Carlos Emilio ^[1] ; Orsi, Fernanda Andrade ^[1] ; de Lima, Franciele ^[1] ; Annichinno-Bizzacchi, Joyce M. ^{[3, 1]} ; De Paula, Erich Vinicius ^{[3, 1]}

Affiliation

^[1] Univ Estadual Campinas, Sch Med Sci, Campinas, SP - Brazil

^[2] Univ Fed Piaui, Parnaiba, PI - Brazil

^[3] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 14, n. 12 DEC 31 2019.
• Web of Science Citations: 0

Abstract

The biological relevance of fibrinolysis to the host response to sepsis is illustrated by pathogens such as S. pyogenes and Y. pestis, whose virulence factors are proteins that challenge the balance between pro- and anti-fibrinolytic factors of the host, and by the consistent finding of hypofibrinolysis in the early stages of sepsis. Whether this hypofibrinolytic response is beneficial or detrimental to the host, by containing the spread of pathogens while at the same time limiting the access of immune cell to infectious foci, is still a matter of debate. Tranexamic acid (TnxAc) is an antifibrinolytic agent that is being increasingly used to prevent and control bleeding in conditions such as elective orthopedic surgery, trauma, and postpartum-hemorrhage, which are frequently followed by infection and sepsis. Here we used a model of polymicrobial sepsis to evaluate whether hypofibrinolysis induced by TnxAc influenced survival, tissue injury and pathogen spread. Mice were treated with two doses of TnxAc bid for 48h, and then sepsis was induced by cecal ligation and puncture. Despite the induction of hypofibrinolysis by TnxAc, no difference could be observed in survival, tissue injury (measured by biochemical and histological parameters), cytokine levels or pathogen spread. Our results contribute with a new piece of data to the understanding of the complex interplay between fibrinolysis and innate immunity. While our results do not support the use of TnxAc in sepsis, they also address the thrombotic safety of TnxAc, a low cost and widely used agent to prevent bleeding. (AU)

• FAPESP's process: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders
• Grantee: Joyce Maria Annichino-Bizzacchi
• Support Opportunities: Research Projects - Thematic Grants