Factor III
Summary
Factor III, also known as tissue factor (thromboplastin), is a membrane-bound glycoprotein that initiates the extrinsic pathway of the coagulation cascade. It is released by damaged endothelial cells and subendothelial tissue upon vascular injury, binding Factor VII to trigger clot formation. It is also the key reagent used in the PT/INR laboratory test.
Detail
Tissue factor (TF/Factor III) is a transmembrane glycoprotein expressed on subendothelial cells, fibroblasts, and pericytes that is normally sequestered from blood. When vascular injury occurs, TF is exposed to circulating blood and binds activated Factor VII (or Factor VII itself, which it then activates) to form the TF-VIIa complex. This complex activates Factor X (and also Factor IX), initiating the extrinsic pathway of coagulation, which converges with the intrinsic pathway at the common pathway (Factor X activation leading to thrombin and fibrin generation). Clinically, TF is the basis for the prothrombin time (PT) test—thromboplastin reagent (tissue factor plus phospholipids) is added to plasma to measure the extrinsic and common pathway function, used to monitor warfarin therapy via the INR. Tissue factor is also implicated in pathologic states: excessive TF exposure (e.g., in sepsis, malignancy, trauma) can trigger disseminated intravascular coagulation (DIC). Tumor cells may overexpress TF, contributing to cancer-associated thrombosis (Trousseau syndrome). Understanding Factor III's role is essential for grasping the extrinsic pathway's speed and importance in initiating hemostasis in vivo, compared with the intrinsic pathway's role in amplification.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Guyton and Hall Textbook of Medical Physiology
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