Disseminated intravascular coagulation

Gando, Satoshi; Levi, Marcel; Toh, Cheng‐Hock

doi:10.1038/nrdp.2016.37

Cited by 449 publications

(517 citation statements)

References 166 publications

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“…High cytokine levels are associated with the severity of sepsis and development of disseminated intravascular coagulation (for review see Gando et al, 2016). Interestingly, we found markedly higher levels of thrombin-antithrombin (TAT) complexes in plasma from

{P 2 X}_{7}^{- / -}

compared to

{P 2 X}_{7}^{+ / +}

mice (Figure 3B), which indicates enhanced activation of the coagulation cascade in these mice.…”

Section: Resultsmentioning

confidence: 99%

P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli

Greve

Skals

Fagerberg

et al. 2017

Front. Cell. Infect. Microbiol.

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α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Since free hemoglobin in the blood is known to be associated with a worse outcome in sepsis one could speculate that inhibition of P2X receptors would ameliorate the course of sepsis. Surprisingly, this study demonstrates that P2X1−/− and P2X4−/− mice are exceedingly sensitive to sepsis with uropathogenic E. coli. These mice have markedly lower survival, higher cytokine levels and activated intravascular coagulation. Quite the reverse is seen in P2X1−/− mice, which had markedly lower cytokine levels and less coagulation activation compared to controls after exposure to uropathogenic E. coli. The high cytokine levels in the P2X7−/− mouse are unexpected, since P2X7 is implicated in caspase-1-dependent IL-1β production. Here, we demonstrate that IL-1β production during sepsis with uropathogenic E. coli is mediated by caspase-8, since caspase-8 and RIPK3 double knock out mice show substantially lower cytokine during sepsis and increased survival after injection of TNFα. These data support that P2X7 and P2X4 receptor activation has a protective effect during severe E. coli infection.

show abstract

{P 2 X}_{7}^{- / -}

compared to

{P 2 X}_{7}^{+ / +}

mice (Figure 3B), which indicates enhanced activation of the coagulation cascade in these mice.…”

Section: Resultsmentioning

confidence: 99%

P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli

Greve

Skals

Fagerberg

et al. 2017

Front. Cell. Infect. Microbiol.

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show abstract

“…DIC developing as a complication of sepsis is characterized by an elevation of plasmin activator inhibitor-1 (PAI-1) leading to alterations in fibrinolysis and microvascular thrombotic complications (47). Although microvascular injury in trauma and hemorrhagic shock may bear some similarities to DIC, the impairment in hemostasis seen from hyperfibrinolysis in trauma is contrasted from sepsis (37) which seldom has a bleeding tendency but is more frequently characterized by thrombotic sequelae.…”

Section: Pro: Coagulopathy Should Be a Therapeutic Target In Criticalmentioning

confidence: 99%

Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?

Moore

Winfield

Aibiki

et al. 2017

Shock

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Coagulopathy is a common and vexing clinical problem in critically ill patients. Recently, major advances focused on the treatment of coagulopathy in trauma and sepsis have emerged. However, the targeting of coagulopathy with blood product transfusion and drugs directed at attenuating the physiologic response to these conditions have major potential risk to the patient. Therefore, the identification of coagulopathy as a clinical target is an area of uncertainty and controversy. In order to analyze the state of the science regarding coagulopathy in critical illness, a symposium addressing the problem was organized at the 39th annual meeting of the Shock Society in the summer of 2016. This manuscript synthesizes the viewpoints of the four expert panelists at the debate and presents an overview of the potential positive and negative consequences of targeting coagulopathy in trauma and sepsis.

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“…Platelet dysfunction arises and inhibitors of coagulation are depleted. These complex changes often render the patient susceptible to bleeding (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Tie2 protects the vasculature against thrombus formation in systemic inflammation

Higgins¹,

Ceunynck

Kellum

et al. 2018

Journal of Clinical Investigation

100

109

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Disseminated intravascular coagulation

Cited by 449 publications

References 166 publications

P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli

P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli

Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?

Tie2 protects the vasculature against thrombus formation in systemic inflammation

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