In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein called tissue factor (TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumor necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon exposure to blood and platelets, TF binds with activated factor VIIa (normally present in trace amounts in the blood), forming the extrinsic tenase complex. This complex further activates factor IX and X to IXa and Xa, respectively, leading to the common coagulation pathway and the subsequent formation of thrombin and fibrin.