Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid

Asakura, Hitoshi; Sano, Yoko; Yoshida, Tomotaka; Omote, Mika; Ontachi, Yasuo; Mizutani, Tomoe; Yamazaki, Masahide; Morishita, Eriko; Takami, Akiyoshi; Miyamoto, Ken‐ichi; Nakao, Shinji

doi:10.1007/s00134-004-2349-7

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…34 However, glomerular fibrin deposition (GFD) was also demonstrated to be closely related to organ dysfunction in LPS-induced sepsis. 35 In our present study, LPS infusion lead to a significant glomerular mesangial expansion and also an increase of GFD. Furthermore, the pathological finding could be attenuated by curcumin administration associated with an improvement of coagulation profile.…”

supporting

confidence: 64%

Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia

Chen

Kuo

Chai

et al. 2007

Journal of Endotoxin Research

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Disseminated intravascular coagulation (DIC) is a lethal situation in severe infections, characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. Current clinical trials are not promising. In this study, we investigated the protective effect of curcumin in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by sustained infusion of LPS (10 mg/kg body weight) for 4 h through the tail vein. Curcumin (60 mg/kg body weight) was given intraperitoneally 3 h before LPS infusion. Results showed that, in vivo, curcumin reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-alpha levels and the consumption of peripheral platelets and plasma fibrinogen. Furthermore, in vivo curcumin also has the effect of preventing the formation of fibrin deposition in the glomeruli of kidney. These results reveal the therapeutic potential of curcumin in infection-related coagulopathy of DIC.

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supporting

confidence: 64%

Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia

Chen

Kuo

Chai

et al. 2007

Journal of Endotoxin Research

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“…Of note, recent studies using TnxAc in therapeutic doses failed to show any procoagulant effect of this agent [37], although increased TAT levels have been described in TnxAc-treated patients in the past [38]. Since indirect markers of thrombin generation such as TAT and D-dimer are early and sensitive markers of DIC, and TnxAc has been shown to increase organ damage in murine endotoxemia [39], the observed increase in TAT levels in TnxAc-treated mice do not allow us to exclude that TnxAc could be deleterious during sepsis. However, the rate of microvascular thrombosis was not increased in TnxAc-treated mice 24 hours after polymicrobial sepsis, and that no clinically evident bleeding was observed in our 7-day survival experiments (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…The fact that fibrinolytic activation plays an important role in DIC models has been confirmed by evaluating the effects of administering tranexamic acid (TA), an antifibrinolytic drug, in both models [ 27 , 28 ]. In the TF-induced DIC model, although hepatorenal dysfunction is seldom observed (hematuria occurs at a high frequency), when TA is administered, severe organ dysfunction similar to that in the LPS model is observed (the hematuria disappears).…”

Section: Reviewmentioning

confidence: 99%

Classifying types of disseminated intravascular coagulation: clinical and animal models

2014

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Disseminated intravascular coagulation (DIC) has a common pathogenesis in terms of persistent widespread activation of coagulation in the presence of underlying disease, but the degree of fibrinolytic activation often differs by DIC type. DIC with suppressed fibrinolysis is a DIC type usually seen in sepsis. Coagulation activation is severe, but fibrinolytic activation is mild. DIC with enhanced fibrinolysis is a DIC type usually seen in acute promyelocytic leukemia (APL). Both coagulation activation and fibrinolytic activation are severe. DIC with balanced fibrinolysis is a DIC type usually seen in solid tumors, with an intermediate pathogenesis between the above two types. In animal DIC models, lipopolysaccharide (LPS)-induced models are similar to suppressed-fibrinolytic-type DIC, whereas tissue factor (TF)-induced models are similar to enhanced fibrinolytic/balanced fibrinolytic DIC. Appropriate diagnosis and treatment may also differ depending on the DIC type.

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Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid

Cited by 17 publications

References 30 publications

Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia

Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia

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

Classifying types of disseminated intravascular coagulation: clinical and animal models

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