The coagulation cascade in sepsis.
Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of the anticoagulant Protein C pathway also plays an important role in the modulation of coagulation and inflammation in sepsis. Recent advances in the understanding of pathogenetic mechanisms of coagulation and fibrinolysis in sepsis may have therapeutic implications. Recombinant human activated protein C (rhAPC) is currently the only pharmacologic therapy that has been shown to reduce mortality in adults with severe sepsis, highlighting the importance of coagulation and fibrinolysis as a therapeutic target in sepsis. This review summarizes recent basic and clinical findings with regard to the role of the coagulation cascade in sepsis and explores potential therapeutic targets in the coagulation and fibrinolytic pathways in the management of sepsis.
Wang
Ling
L
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Bastarache
Julie A
JA
Ware
Lorraine B
LB
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D016503:Drug Delivery Systems; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011486:Protein C / Q000378:metabolism / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D013925:Thromboplastin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D011994:Recombinant Proteins; D005337:Fibrin; D013925:Thromboplastin