Coagulation in severe sepsis: a central role for thrombomodulin and activated protein C.
OBJECTIVE
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.


METHODS
Published research abstracts and review articles on the experimental and clinical investigation of the pathophysiology of disseminated intravascular coagulation in sepsis.


METHODS
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.
Faust
S N
SN
Department of Paediatrics, Imperial College of Medicine at St Mary's, London, UK.
Heyderman
R S
RS
Levin
M
M
D000925:Anticoagulants / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology; D004198:Disease Susceptibility; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007249:Inflammation; D011486:Protein C / Q000502:physiology* / Q000627:therapeutic use*; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000737:chemistry / Q000502:physiology* / Q000627:therapeutic use*; D014661:Vasoconstriction / Q000502:physiology
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011486:Protein C; D018180:Thrombomodulin