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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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Coagulation abnormalities in pneumonia (Pneu) and acute respiratory distress syndrome (ARDS; n = 222). SPV, spontaneous ventilation; MV, mechanical ventilation. Adapted from Günther et al [17].
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Figure 6: Coagulation abnormalities in pneumonia (Pneu) and acute respiratory distress syndrome (ARDS; n = 222). SPV, spontaneous ventilation; MV, mechanical ventilation. Adapted from Günther et al [17].

Mentions: Coagulation abnormalities can occur in all types of infection, including both Gram-positive and Gram-negative bacterial infections [13,14,15], or even in the absence of infection, such as in inflammatory states secondary to trauma or neurosurgery [16]. Interestingly, they can also occur in patients with localized disease, such as those with respiratory infection [17]. In a study by Günther et al [17], procoagulant activity in bronchial lavage fluid from patients with pneumonia or acute respiratory distress syndrome was found to be increased compared with that from control individuals, with a correlation between the severity of respiratory failure and level of coagulant activity (Fig. 6).


Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology.

Vincent JL - Crit Care (2001)

Coagulation abnormalities in pneumonia (Pneu) and acute respiratory distress syndrome (ARDS; n = 222). SPV, spontaneous ventilation; MV, mechanical ventilation. Adapted from Günther et al [17].
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Coagulation abnormalities in pneumonia (Pneu) and acute respiratory distress syndrome (ARDS; n = 222). SPV, spontaneous ventilation; MV, mechanical ventilation. Adapted from Günther et al [17].
Mentions: Coagulation abnormalities can occur in all types of infection, including both Gram-positive and Gram-negative bacterial infections [13,14,15], or even in the absence of infection, such as in inflammatory states secondary to trauma or neurosurgery [16]. Interestingly, they can also occur in patients with localized disease, such as those with respiratory infection [17]. In a study by Günther et al [17], procoagulant activity in bronchial lavage fluid from patients with pneumonia or acute respiratory distress syndrome was found to be increased compared with that from control individuals, with a correlation between the severity of respiratory failure and level of coagulant activity (Fig. 6).

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