Coagulation in severe sepsis: A central role for thrombomodulin and activated protein C

OBJECTIVES: To review the mechanisms that cause coagulation abnormalities in sepsis, focusing on the interaction between the vascular endothelium and the circulating coagulation factors, particularly the role of the protein C pathway and thrombomodulin. DATA SOURCES/STUDY SELECTION: Published research abstracts and review articles on the experimental and clinical investigation of the pathophysiology of disseminated intravascular coagulation in sepsis. DATA EXTRACTION AND SYNTHESIS: The data provide increasing evidence that the coagulopathy seen in sepsis is a result of a complex imbalance of pro- and anticoagulant pathways. Whereas previous research has largely studied events in the plasma, it is now apparent that reactions on cell surfaces such as the vascular endothelium are important in the control of the regulatory pathways. CONCLUSIONS: The plasma components of the protein C pathway are down-regulated in sepsis. Decreased thrombomodulin expression may cause defective function of the endothelial component of this pathway in septic patients. Treatments must be designed to overcome any functional defect.