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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

Plasma plasminogen activator inhibitor-1 (PAI-1) levels correlate with multiple organ dysfunction scores using the sequential organ failure assessment (SOFA) score in sepsis-induced DIC patients. DIC patients were classified into four groups according to PAI-1 levels at the time of DIC diagnosis (<30 ng/mL, 30–60 ng/mL, 60–90 ng/mL, and >90 ng/mL), and the groups were compared with respect to SOFA scores. Data are presented as the mean ± SEM. Reprinted with modifications from International Journal of Hematology [46].
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Fig3: Plasma plasminogen activator inhibitor-1 (PAI-1) levels correlate with multiple organ dysfunction scores using the sequential organ failure assessment (SOFA) score in sepsis-induced DIC patients. DIC patients were classified into four groups according to PAI-1 levels at the time of DIC diagnosis (<30 ng/mL, 30–60 ng/mL, 60–90 ng/mL, and >90 ng/mL), and the groups were compared with respect to SOFA scores. Data are presented as the mean ± SEM. Reprinted with modifications from International Journal of Hematology [46].

Mentions: The fibrinolysis system is mainly mediated by plasminogen activators-plasmin system and regulated by a principal inhibitor PAI-1. Numerous studies have consistently found that a marked increase in PAI-1 results in a fibrinolytic shutdown in endotoxemia or sepsis, although a simultaneous increase in tPA often occurs [44]. Indeed, fibrinolysis is suppressed by increased PAI-1 levels in the plasma of DIC patients exhibiting SIRS with sepsis or trauma. Although there may be some fibrinolytic activity in response to the extensive formation of fibrin, the levels of this activity are too low to counteract the systemic deposition of fibrin clots in SIRS. PAI-1 expression was localized primarily to endothelial cells at all levels of the vasculature in endotoxemic animal models, suggesting that plasma PAI-1 originates from endothelial cells [45]. High levels of PAI-1 have been implicated as predictive for an adverse outcome in severe sepsis, and suppressed fibrinolysis is one of the most important predictors of multiple organ dysfunction during sepsis-induced DIC (Figure 3) [46]. Additional measurements were made at the time of ICU admission independently discriminated between patients who developed DIC from those who did not, including increased levels of PAI-1, as well as thrombin-antithrombin complex, a biomarker for activation of coagulation, and decreased protein C as an indicator for consumption of coagulation factor [47].Figure 3


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

Madoiwa S - J Intensive Care (2015)

Plasma plasminogen activator inhibitor-1 (PAI-1) levels correlate with multiple organ dysfunction scores using the sequential organ failure assessment (SOFA) score in sepsis-induced DIC patients. DIC patients were classified into four groups according to PAI-1 levels at the time of DIC diagnosis (<30 ng/mL, 30–60 ng/mL, 60–90 ng/mL, and >90 ng/mL), and the groups were compared with respect to SOFA scores. Data are presented as the mean ± SEM. Reprinted with modifications from International Journal of Hematology [46].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Plasma plasminogen activator inhibitor-1 (PAI-1) levels correlate with multiple organ dysfunction scores using the sequential organ failure assessment (SOFA) score in sepsis-induced DIC patients. DIC patients were classified into four groups according to PAI-1 levels at the time of DIC diagnosis (<30 ng/mL, 30–60 ng/mL, 60–90 ng/mL, and >90 ng/mL), and the groups were compared with respect to SOFA scores. Data are presented as the mean ± SEM. Reprinted with modifications from International Journal of Hematology [46].
Mentions: The fibrinolysis system is mainly mediated by plasminogen activators-plasmin system and regulated by a principal inhibitor PAI-1. Numerous studies have consistently found that a marked increase in PAI-1 results in a fibrinolytic shutdown in endotoxemia or sepsis, although a simultaneous increase in tPA often occurs [44]. Indeed, fibrinolysis is suppressed by increased PAI-1 levels in the plasma of DIC patients exhibiting SIRS with sepsis or trauma. Although there may be some fibrinolytic activity in response to the extensive formation of fibrin, the levels of this activity are too low to counteract the systemic deposition of fibrin clots in SIRS. PAI-1 expression was localized primarily to endothelial cells at all levels of the vasculature in endotoxemic animal models, suggesting that plasma PAI-1 originates from endothelial cells [45]. High levels of PAI-1 have been implicated as predictive for an adverse outcome in severe sepsis, and suppressed fibrinolysis is one of the most important predictors of multiple organ dysfunction during sepsis-induced DIC (Figure 3) [46]. Additional measurements were made at the time of ICU admission independently discriminated between patients who developed DIC from those who did not, including increased levels of PAI-1, as well as thrombin-antithrombin complex, a biomarker for activation of coagulation, and decreased protein C as an indicator for consumption of coagulation factor [47].Figure 3

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