Article Text
Statistics from Altmetric.com
The role and source of tissue factor
A large body of evidence has shown that systemic coagulopathy is a key event in severe systemic inflammation, such as that which occurs in sepsis.1 Systemic coagulopathy is the net result of activation of coagulation and defective systems of natural inhibition of coagulation, on the one hand, and attenuation of fibrinolysis on the other. Activation of coagulation is primarily driven by the extrinsic coagulation pathway which starts with expression of tissue factor (TF) on mononuclear cells and endothelial cells. TF then binds and activates factor VII which activates downstream coagulation cascades.2,3 Mechanisms that regulate the coagulation pathway under normal conditions involve natural inhibitors of coagulation, including activated protein C (APC), antithrombin (AT) and tissue factor pathway inhibitor (TFPI). In general, they all interfere with the TF–factor VIIa-induced activation of coagulation, but on different levels. In patients with sepsis, increased coagulant activity is not sufficiently counterbalanced by these natural inhibitors. In addition, a rapid sustained increase in synthesis of plasminogen activator inhibitor (PAI)-1 is present during the septic response. PAI-1 is the main inhibitor of tissue-type and urokinase-type plasminogen activator (tPA and uPA) which activate the fibrinolytic system. The importance of systemic coagulopathy with sepsis has been established in experimental studies and in the randomised, prospective, double-blind, placebo-controlled PROWESS trial in which infusion of recombinant human (rh)-APC resulted in improved survival of patients with severe sepsis.4
LOCAL COAGULOPATHY WITH ACUTE LUNG INJURY
Coagulopathy with acute lung injury and/or pneumonia
Recent studies have clearly shown that prominent changes in local fibrin turnover are an important feature of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and pulmonary infection. The profile and extent of these changes vary with the severity of inflammation: in severe pneumonia …