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The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness.

Esmon CT - Crit Care (2001)

Bottom Line: Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects.When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences.In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA. Charles-Esmon@omrf.ouhsc.edu

ABSTRACT
Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in activation of Protein C and initiation of the Activated Protein C anticoagulant pathway, a process that is augmented by the endothelial cell Protein C receptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-inflammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also been shown to modulate inflammation. When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

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Related in: MedlinePlus

The inflammation-coagulation autoamplification loop. Adapted from Esmon et al [10].
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Figure 4: The inflammation-coagulation autoamplification loop. Adapted from Esmon et al [10].

Mentions: If there were no mechanisms to disrupt the amplification of coagulation by inflammation, and vice versa, then the ensuing vicious cycle would have a catastrophic effect, leading ultimately to death (Fig. 4) [10]. It was hypothesized, therefore, that endogenous Activated Protein C interferes with these amplification loops by modulating both coagulation and inflammation, which differentiates it from other types of anticoagulants, and that Protein C depletion may occur in severe sepsis [11].


The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness.

Esmon CT - Crit Care (2001)

The inflammation-coagulation autoamplification loop. Adapted from Esmon et al [10].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3300084&req=5

Figure 4: The inflammation-coagulation autoamplification loop. Adapted from Esmon et al [10].
Mentions: If there were no mechanisms to disrupt the amplification of coagulation by inflammation, and vice versa, then the ensuing vicious cycle would have a catastrophic effect, leading ultimately to death (Fig. 4) [10]. It was hypothesized, therefore, that endogenous Activated Protein C interferes with these amplification loops by modulating both coagulation and inflammation, which differentiates it from other types of anticoagulants, and that Protein C depletion may occur in severe sepsis [11].

Bottom Line: Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects.When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences.In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA. Charles-Esmon@omrf.ouhsc.edu

ABSTRACT
Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in activation of Protein C and initiation of the Activated Protein C anticoagulant pathway, a process that is augmented by the endothelial cell Protein C receptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-inflammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also been shown to modulate inflammation. When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.

Show MeSH
Related in: MedlinePlus