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Severe sepsis is
associated with three integrated components:
Infection with the systemic activation of inflammation. During
progression of sepsis, a wide variety of proinflammatory cytokines is
released. Endotoxin induces rapid increases in the levels of tumor
necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) in
experimental models of sepsis. These proinflammatory cytokines are linked
to the development of the clinical signs of sepsis. Release of
proinflammatory cytokines is associated with endothelial injury and
vascular bed-specific changes in the thrombogenicity of the
endothelium.These can include increased tissue factor (TF) expression in a
subset of endothelial cells and release of plasminogen activator
inhibitor-1 (PAI-1).
Activation of coagulation. Inflammatory changes trigger the extrinsic
pathway of coagulation. Activation of coagulation in patients with sepsis
is not always disseminated intravascular coagulation. Instead, in most
patients, it is a subclinical activation of the hemostatic system as
indicated by changes in commonly measured hemostatic parameters.
Experimentally, there are increases in thrombin-antithrombin (TAT)
complexes. Clinical laboratory findings include significant increases in
D-dimer, a marker of coagulation and associated fibrinolysis.
Impairment of fibrinolysis. In patients with sepsis, plasminogen
levels fall rapidly while antiplasmin levels remain normal. This decreases
the normal fibrinolytic response. Fibrinolysis is further impaired by
release of PAI-1 and the generation of increased amounts of thrombin-activatable
fibrinolysis inhibitor (TAFI). Although plasminogen/antiplasmin ratio and
PAI-1 levels remain abnormal in nonsurviving patients, they tend to
normalize in survivors.
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van Deventer SJH, Buller HR, ten Cate JW, et al. Experimental endotoxemia
in humans: analysis of cytokine release and coagulation, fibrinolytic, and
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fibrinolysis in critically ill patients with sepsis and septic shock.
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