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Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus

Relationships between the SOFA score and cross-linked fibrin degradation product by leukocyte elastase (e-XDPs) levels in sepsis-induced DIC patients. Patients with sepsis-induced DIC were classified into four groups with e-XDPs levels (<3 U/mL, 3–10 U/mL, 10–30 U/mL, >30 U/mL) at the time of DIC diagnosed, and the groups ((A) D-dimer and (B) e-XDP) were compared with respect to SOFA scores. Data are presented as means ± SEM. Reprinted with modifications from Thrombosis Research [66].
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Fig4: Relationships between the SOFA score and cross-linked fibrin degradation product by leukocyte elastase (e-XDPs) levels in sepsis-induced DIC patients. Patients with sepsis-induced DIC were classified into four groups with e-XDPs levels (<3 U/mL, 3–10 U/mL, 10–30 U/mL, >30 U/mL) at the time of DIC diagnosed, and the groups ((A) D-dimer and (B) e-XDP) were compared with respect to SOFA scores. Data are presented as means ± SEM. Reprinted with modifications from Thrombosis Research [66].

Mentions: Exposure to inflammatory mediators and interaction with leukocytes causes endothelial activation and dysfunction, directly or indirectly [62]. However, leukocyte elastase has been found to degrade cross-linked fibrin and to yield molecular species distinct from those generated by plasmin [63]. Thus, leukocyte elastase-mediated fibrinolysis is activated to varying degrees, depending on the extent of systemic inflammation (Figure 4) [64]. These alternative systems for fibrinolysis, comprised of proteases other than plasmin and their interactions with the plasminogen activators-plasmin systems, have been thought to play crucial roles in the fibrin lysis of clots in sepsis-induced DIC [65,66]. The evaluation of leukocyte elastase-mediated fibrinolysis and regulation of its activity by specific inhibitors could improve the poor outcomes common to patients with sepsis-induced DIC [67].Figure 4


Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC.

Madoiwa S - J Intensive Care (2015)

Relationships between the SOFA score and cross-linked fibrin degradation product by leukocyte elastase (e-XDPs) levels in sepsis-induced DIC patients. Patients with sepsis-induced DIC were classified into four groups with e-XDPs levels (<3 U/mL, 3–10 U/mL, 10–30 U/mL, >30 U/mL) at the time of DIC diagnosed, and the groups ((A) D-dimer and (B) e-XDP) were compared with respect to SOFA scores. Data are presented as means ± SEM. Reprinted with modifications from Thrombosis Research [66].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940964&req=5

Fig4: Relationships between the SOFA score and cross-linked fibrin degradation product by leukocyte elastase (e-XDPs) levels in sepsis-induced DIC patients. Patients with sepsis-induced DIC were classified into four groups with e-XDPs levels (<3 U/mL, 3–10 U/mL, 10–30 U/mL, >30 U/mL) at the time of DIC diagnosed, and the groups ((A) D-dimer and (B) e-XDP) were compared with respect to SOFA scores. Data are presented as means ± SEM. Reprinted with modifications from Thrombosis Research [66].
Mentions: Exposure to inflammatory mediators and interaction with leukocytes causes endothelial activation and dysfunction, directly or indirectly [62]. However, leukocyte elastase has been found to degrade cross-linked fibrin and to yield molecular species distinct from those generated by plasmin [63]. Thus, leukocyte elastase-mediated fibrinolysis is activated to varying degrees, depending on the extent of systemic inflammation (Figure 4) [64]. These alternative systems for fibrinolysis, comprised of proteases other than plasmin and their interactions with the plasminogen activators-plasmin systems, have been thought to play crucial roles in the fibrin lysis of clots in sepsis-induced DIC [65,66]. The evaluation of leukocyte elastase-mediated fibrinolysis and regulation of its activity by specific inhibitors could improve the poor outcomes common to patients with sepsis-induced DIC [67].Figure 4

Bottom Line: Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis.The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC).Leukocytes exhibit the first-line response to microorganisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, 1-14-17, Mita, Minato-ku, Tokyo 108-0073 Japan ; Department of Clinical Laboratory Medicine, Jichi Medical University, 3311-1, Yakushi-ji, Shimotsuke, Tochigi 329-0498 Japan.

ABSTRACT
Endothelial cells are highly active, sensing and responding to signals from extracellular environments. They act as gatekeepers, mediating the recruitment and extravasation of proinflammatory leukocytes to the sites of tissue damage or infection. Endothelial cells participate in fibrinolysis by secreting tissue-type plasminogen activator, which converts plasminogen to active enzyme plasmin through constitutive and regulated pathways. Fibrinolysis systems and inflammation are tightly linked, as both responses are major host defense systems against both healing processes of tissue repair as well as pathogenic microorganisms. Endothelial cell dysfunction is one of the early signs of systemic inflammation, and it is a trigger of multiple organ failure in sepsis. The marked increase in plasminogen activator inhibitor-1 level causes fibrinolytic shutdown in endotoxemia or sepsis and is one of the most important predictors of multiple organ dysfunction during sepsis-induced disseminated intravascular coagulation (DIC). Leukocytes exhibit the first-line response to microorganisms. Leukocyte-derived elastase degrades cross-linked fibrin to yield molecular species distinct from those generated by plasmin. The alternative systems for fibrinolysis that interact with the plasminogen activator-plasmin systems may play crucial roles in the lysis of fibrin clots in sepsis-induced DIC.

No MeSH data available.


Related in: MedlinePlus