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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1687.)
© 2007 American Heart Association, Inc.

Brief Reviews

Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis

Nigel Mackman; Rachel E. Tilley; Nigel S. Key

From the Departments of Immunology & Cell Biology (N.M. R.E.T.), The Scripps Research Institute, La Jolla, Calif; and the Department of Medicine (N.S.K.), University of North Carolina at Chapel Hill.

Correspondence to Nigel Mackman, PhD, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30-3040, La Jolla, CA 92037. E-mail nmackman{at}scripps.edu

Hemostasis requires both platelets and the coagulation system. At sites of vessel injury, bleeding is minimized by the formation of a hemostatic plug consisting of platelets and fibrin. The traditional view of the regulation of blood coagulation is that the initiation phase is triggered by the extrinsic pathway, whereas amplification requires the intrinsic pathway. The extrinsic pathway consists of the transmembrane receptor tissue factor (TF) and plasma factor VII/VIIa (FVII/FVIIa), and the intrinsic pathway consists of plasma FXI, FIX, and FVIII. Under physiological conditions, TF is constitutively expressed by adventitial cells surrounding blood vessels and initiates clotting. In addition so-called blood-borne TF in the form of cell-derived microparticles (MPs) and TF expression within platelets suggests that TF may play a role in the amplification phase of the coagulation cascade. Under pathologic conditions, TF is expressed by monocytes, neutrophils, endothelial cells, and platelets, which results in an elevation of the levels of circulating TF-positive MPs. TF expression within the vasculature likely contributes to thrombosis in a variety of diseases. Understanding how the extrinsic pathway of blood coagulation contributes to hemostasis and thrombosis may lead to the development of safe and effective hemostatic agents and antithrombotic drugs.

The extrinsic pathway of blood coagulation is required for thrombosis. However, under pathologic conditions, TF expression within the vasculature leads to thrombosis. Development of safe and effective hemostatic agents and antithrombotic drugs requires a better understanding of the role of TF and FVIIa in hemostasis and thrombosis.

Key Words: coagulation • arterial thrombosis • deep vein thrombosis

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