What is Sepsis?  Coagulopathy

      
       

 

          
       

The activation of the coagulation cascades appears to be an essential component in the development of multi-organ failure. It is important that you are aware of this, as current therapies for sepsis specifically target these cascades for modulation (15). If you are bored senseless by discussions of clotting cascades, then skip this section.

We know that in sepsis (figure 5), an overwhelming inflammatory response causes extensive collateral damage to the host’s microcirculation. Damage to the endothelium exposes a procoagulant factor known as “tissue factor”. This exists in the subendothelial space, and it has a role in reparation after tissue damage in all human beings. However, in sepsis, the exposure occurs on a mammoth scale. Tissue factor binds to activated factor VII. The resulting complex activates in turn factors IX and X. Factor X converts prothrombin into thrombin, which cleaves fibrinogen into fibrin, a blood clot. At the same time, the fibrinolytic system is inhibited. Cytokines and thrombin stimulate the release of  plasminogen-activator inhibitor-1 (PAI-1), from platelets and the endothelium. In the human body, when a clot forms, it is ultimately broken down plasmin, which is activated by tissue plasminogen activator (TPA) [from plasminogen]. PAI-1 inhibits TPA.

Thrombin, itself, is an activator of inflammation and inhibitor of fibrinolysis. The latter is achieved by the activation of TAFI (thrombin-activatable fibrinolysis inhibitor).

Thrombomodulin, another modulator of fibrinolyis, is impaired by inflammation and endothelial injury. The function of this compound is to activate protein C. Activated protein C modifies the inflammatory and coagulant response at several different levels; a deficiency occurs due to inhibition of thrombomodulin in sepsis.

The Imbalance of coagulation and fibrinolysis in sepsis
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References

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THIS TUTORIAL BY PATRICK NELIGAN MD, UNIVERSITY OF PENNSYLVANIA

        
       

 

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