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


Autoři: Yzabella Alves Campos Nogueira aff001;  Loredana Nilkenes Gomes da Costa aff001;  Carlos Emilio Levy aff001;  Fernanda Andrade Orsi aff001;  Franciele de Lima aff001;  Joyce M. Annichinno-Bizzacchi aff001;  Erich Vinicius De Paula aff001
Působiště autorů: School of Medical Sciences, University of Campinas, Campinas, SP, Brazil aff001;  Federal University of Piaui, Parnaiba, PI, Brazil aff002;  Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226871

Souhrn

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 post-partum-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.

Klíčová slova:

Blood – Blood plasma – Fibrinolysis – Inflammation – Kidneys – Mouse models – Sepsis – Thrombosis


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Článek vyšel v časopise

PLOS One


2019 Číslo 12