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Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis.

Opal SM, Esmon CT - Crit Care (2002)

Bottom Line: Microbial invasion poses an immediate threat to survival, and a vigorous defense response ensues in an effort to clear the pathogen from the internal milieu of the host.It is becoming increasingly clear that coagulation and innate immunity have coevolved from a common ancestral substrate early in eukaryotic development, and that these systems continue to function as a highly integrated unit for survival defense following tissue injury.The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review.

View Article: PubMed Central - PubMed

Affiliation: Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA. Steven_Opal@brown.edu

ABSTRACT
The innate immune response system is designed to alert the host rapidly to the presence of an invasive microbial pathogen that has breached the integument of multicellular eukaryotic organisms. Microbial invasion poses an immediate threat to survival, and a vigorous defense response ensues in an effort to clear the pathogen from the internal milieu of the host. The innate immune system is able to eradicate many microbial pathogens directly, or innate immunity may indirectly facilitate the removal of pathogens by activation of specific elements of the adaptive immune response (cell-mediated and humoral immunity by T cells and B cells). The coagulation system has traditionally been viewed as an entirely separate system that has arisen to prevent or limit loss of blood volume and blood components following mechanical injury to the circulatory system. It is becoming increasingly clear that coagulation and innate immunity have coevolved from a common ancestral substrate early in eukaryotic development, and that these systems continue to function as a highly integrated unit for survival defense following tissue injury. The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review.

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Related in: MedlinePlus

The major coagulation factors and the pathways of coagulation activation in sepsis. TF, tissue factor; t-PA, tissue-type plasminogen activator.
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Figure 2: The major coagulation factors and the pathways of coagulation activation in sepsis. TF, tissue factor; t-PA, tissue-type plasminogen activator.

Mentions: This subject was reviewed in considerable detail recently [1,2,3,43,44], and the major clotting parameters that interact in sepsis are shown in Fig. 2. The extrinsic pathway (TF pathway) is the primary mechanism by which thrombin is generated in sepsis, hemostasis and thrombosis. The intrinsic cascade (contact factor pathway) primarily serves an accessory role in amplifying the prothrombotic events that are initiated in sepsis. Thrombin, factor Xa and the TF–factor VIIa complex directly activate endothelial cells, platelets and white blood cells, and induce a proinflammatory response. The inflammatory reaction to tissue injury activates the clotting system, inhibits the endogenous anticoagulants, and attenuates the fibrinolytic response. The net effect within the microcirculation is a procoagulant state, which has major therapeutic implications [16,17,24,45].


Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis.

Opal SM, Esmon CT - Crit Care (2002)

The major coagulation factors and the pathways of coagulation activation in sepsis. TF, tissue factor; t-PA, tissue-type plasminogen activator.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC154114&req=5

Figure 2: The major coagulation factors and the pathways of coagulation activation in sepsis. TF, tissue factor; t-PA, tissue-type plasminogen activator.
Mentions: This subject was reviewed in considerable detail recently [1,2,3,43,44], and the major clotting parameters that interact in sepsis are shown in Fig. 2. The extrinsic pathway (TF pathway) is the primary mechanism by which thrombin is generated in sepsis, hemostasis and thrombosis. The intrinsic cascade (contact factor pathway) primarily serves an accessory role in amplifying the prothrombotic events that are initiated in sepsis. Thrombin, factor Xa and the TF–factor VIIa complex directly activate endothelial cells, platelets and white blood cells, and induce a proinflammatory response. The inflammatory reaction to tissue injury activates the clotting system, inhibits the endogenous anticoagulants, and attenuates the fibrinolytic response. The net effect within the microcirculation is a procoagulant state, which has major therapeutic implications [16,17,24,45].

Bottom Line: Microbial invasion poses an immediate threat to survival, and a vigorous defense response ensues in an effort to clear the pathogen from the internal milieu of the host.It is becoming increasingly clear that coagulation and innate immunity have coevolved from a common ancestral substrate early in eukaryotic development, and that these systems continue to function as a highly integrated unit for survival defense following tissue injury.The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review.

View Article: PubMed Central - PubMed

Affiliation: Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA. Steven_Opal@brown.edu

ABSTRACT
The innate immune response system is designed to alert the host rapidly to the presence of an invasive microbial pathogen that has breached the integument of multicellular eukaryotic organisms. Microbial invasion poses an immediate threat to survival, and a vigorous defense response ensues in an effort to clear the pathogen from the internal milieu of the host. The innate immune system is able to eradicate many microbial pathogens directly, or innate immunity may indirectly facilitate the removal of pathogens by activation of specific elements of the adaptive immune response (cell-mediated and humoral immunity by T cells and B cells). The coagulation system has traditionally been viewed as an entirely separate system that has arisen to prevent or limit loss of blood volume and blood components following mechanical injury to the circulatory system. It is becoming increasingly clear that coagulation and innate immunity have coevolved from a common ancestral substrate early in eukaryotic development, and that these systems continue to function as a highly integrated unit for survival defense following tissue injury. The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review.

Show MeSH
Related in: MedlinePlus