factorIII

Factor III, commonly known as tissue factor (TF) or thromboplastin, is a transmembrane glycoprotein that plays a central role in the initiation of blood coagulation. It is expressed by cells outside the blood vessels, including subendothelial tissues, fibroblasts, and smooth muscle cells, and is exposed to circulating blood after vascular injury.

Mechanism of action: When vascular injury exposes TF to blood, TF binds circulating Factor VII and VIIa to form the TF–VIIa complex. This complex activates Factor X to Xa and Factor IX to IXa, triggering the extrinsic coagulation pathway. Activated Factor Xa, together with Factor V, calcium, and phospholipids, forms the prothrombinase complex that converts prothrombin to thrombin. Thrombin then amplifies clot formation by converting fibrinogen to fibrin and by activating other coagulation factors. The activity of TF–VIIa is regulated by tissue factor pathway inhibitor (TFPI) and other anticoagulant mechanisms.

Structure and gene: TF is encoded by the F3 gene. The protein has an extracellular domain that binds VII/VIIa, a single transmembrane region, and a short cytoplasmic tail. As a cell-surface receptor, TF localizes to sites where it can rapidly engage circulating factors upon injury.

Clinical relevance: Abnormal TF expression is associated with pathological coagulation conditions, including cancer-associated thrombosis and sepsis. In laboratory testing, tissue factor is used in clotting assays to initiate the extrinsic pathway (as thromboplastin). Severe TF deficiency is rare and typically results in bleeding tendencies, while dysregulated TF expression can contribute to disseminated intravascular coagulation.