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. 2001;5(2):S1-5.
doi: 10.1186/cc1332.

Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology

J L Vincent  1
Affiliations

Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology

J L Vincent. Crit Care. 2001.

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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Figures

Figure 1
Figure 1
Central role of thrombin in acute sepsis. PAF, platelet-activating factor; PGI2, prostacyclin; PMN, polymorphonuclear leukocyte.
Figure 2
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.
Figure 3
Figure 3
Procoagulant and anticoagulant substances that are expressed/released by endothelial cells. AT, antithrombin; NO, nitric oxide; PGI2, prostacyclin; TFPI, TF pathway inhibitor.
Figure 4
Figure 4
Protein C levels (% of normal) in patients with meningococcaemia. Adapted from Powars et al [9].
Figure 5
Figure 5
TNF-α levels (normal range <15 pg/ml) and Protein C activity (normal range 60-140%) in malaria. Adapted from Hemmer et al [10].
Figure 6
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].
See this image and copyright information in PMC

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