Limits...
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.

Show MeSH

Related in: MedlinePlus

Experimental model of sepsis in volunteers: Effect of small doses of endotoxin (lipopolysaccharide [LPS]) or TNF on the fibrinolysis system. PAP, plasmin-antiplasmin complex; t-PA, tissue plasminogen activator.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3300083&req=5

Figure 2: Experimental model of sepsis in volunteers: Effect of small doses of endotoxin (lipopolysaccharide [LPS]) or TNF on the fibrinolysis system. PAP, plasmin-antiplasmin complex; t-PA, tissue plasminogen activator.

Mentions: The interaction between coagulation and inflammation has been demonstrated in a number of animal studies in which anticoagulant therapies, including heparin [1,2], antithrombin [3,4], tissue factor (TF) pathway inhibitor [5,6,7] and Activated Protein C [8], were shown to influence the inflammatory response. It is also now clear that both the coagulation and the fibrinolytic systems may be altered in acute sepsis, with the balance tipped in favour of procoagulation (through increased TF and thrombin expression, with decreased activation of thrombomodulin and Protein C) and antifibrinolysis (through plasminogen activator inhibitor [PAI]-1 expression). In experimental models in which very small doses of endotoxin or tumour necrosis factor (TNF) are given to volunteers, there is initially a profibrinolytic response, followed by an antifibrinolytic response, which corresponds to a procoagulant state (Fig. 2).


Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology.

Vincent JL - Crit Care (2001)

Experimental model of sepsis in volunteers: Effect of small doses of endotoxin (lipopolysaccharide [LPS]) or TNF on the fibrinolysis system. PAP, plasmin-antiplasmin complex; t-PA, tissue plasminogen activator.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Experimental model of sepsis in volunteers: Effect of small doses of endotoxin (lipopolysaccharide [LPS]) or TNF on the fibrinolysis system. PAP, plasmin-antiplasmin complex; t-PA, tissue plasminogen activator.
Mentions: The interaction between coagulation and inflammation has been demonstrated in a number of animal studies in which anticoagulant therapies, including heparin [1,2], antithrombin [3,4], tissue factor (TF) pathway inhibitor [5,6,7] and Activated Protein C [8], were shown to influence the inflammatory response. It is also now clear that both the coagulation and the fibrinolytic systems may be altered in acute sepsis, with the balance tipped in favour of procoagulation (through increased TF and thrombin expression, with decreased activation of thrombomodulin and Protein C) and antifibrinolysis (through plasminogen activator inhibitor [PAI]-1 expression). In experimental models in which very small doses of endotoxin or tumour necrosis factor (TNF) are given to volunteers, there is initially a profibrinolytic response, followed by an antifibrinolytic response, which corresponds to a procoagulant state (Fig. 2).

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