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Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology.

Vincent JL - Crit Care (2001)

Bottom Line: Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death.The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin.Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. jlvincen@ulb.ac.be

ABSTRACT
Severe sepsis, defined as sepsis associated with acute organ dysfunction, results from a generalized inflammatory and procoagulant host response to infection. Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death. The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin. In recent years, it has been recognized that chemicals produced by endothelial cells play a key role in the pathogenesis of sepsis. Thrombomodulin on endothelial cells coverts Protein C to Activated Protein C, which has important antithrombotic, profibrinolytic and anti-inflammatory properties. A number of studies have shown that Protein C levels are reduced in patients with severe infection, or even in inflammatory states without infection. Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.

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Related in: MedlinePlus

Central role of thrombin in acute sepsis. PAF, platelet-activating factor; PGI2, prostacyclin; PMN, polymorphonuclear leukocyte.
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Figure 1: Central role of thrombin in acute sepsis. PAF, platelet-activating factor; PGI2, prostacyclin; PMN, polymorphonuclear leukocyte.

Mentions: It is now recognized that acute sepsis involves a complex interaction between the coagulation system and the inflammatory system that may result in organ dysfunction. The molecule that may be considered central to these effects is thrombin. In addition to its well-known procoagulation effects, thrombin may have anticoagulation effects through Protein C activation and induction of prostacyclin (Fig. 1). Thrombin may also cause cell proliferation and inflammation through induction of adhesion molecules and platelet-activating factor activation.


Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology.

Vincent JL - Crit Care (2001)

Central role of thrombin in acute sepsis. PAF, platelet-activating factor; PGI2, prostacyclin; PMN, polymorphonuclear leukocyte.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3300083&req=5

Figure 1: Central role of thrombin in acute sepsis. PAF, platelet-activating factor; PGI2, prostacyclin; PMN, polymorphonuclear leukocyte.
Mentions: It is now recognized that acute sepsis involves a complex interaction between the coagulation system and the inflammatory system that may result in organ dysfunction. The molecule that may be considered central to these effects is thrombin. In addition to its well-known procoagulation effects, thrombin may have anticoagulation effects through Protein C activation and induction of prostacyclin (Fig. 1). Thrombin may also cause cell proliferation and inflammation through induction of adhesion molecules and platelet-activating factor activation.

Bottom Line: Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death.The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin.Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. jlvincen@ulb.ac.be

ABSTRACT
Severe sepsis, defined as sepsis associated with acute organ dysfunction, results from a generalized inflammatory and procoagulant host response to infection. Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death. The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin. In recent years, it has been recognized that chemicals produced by endothelial cells play a key role in the pathogenesis of sepsis. Thrombomodulin on endothelial cells coverts Protein C to Activated Protein C, which has important antithrombotic, profibrinolytic and anti-inflammatory properties. A number of studies have shown that Protein C levels are reduced in patients with severe infection, or even in inflammatory states without infection. Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.

Show MeSH
Related in: MedlinePlus