This Article Full Text Full Text (PDF) All Versions of this Article: 27/8/1687    most recent ATVBAHA.107.141911v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mackman, N. Articles by Key, N. S. Search for Related Content PubMed PubMed Citation Articles by Mackman, N. Articles by Key, N. S.

(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

This article has been cited by other articles:

				R. S. Kasthuri, M. B. Taubman, and N. Mackman Role of Tissue Factor in Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4834 - 4838. [Abstract] [Full Text] [PDF]

				X. Deng, J. P. Luyendyk, P. E. Ganey, and R. A. Roth Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models Pharmacol. Rev., September 1, 2009; 61(3): 262 - 282. [Abstract] [Full Text] [PDF]

				C. J. Lockwood, W. Murk, U. A. Kayisli, L. F. Buchwalder, S.-T. Huang, E. F. Funai, G. Krikun, and F. Schatz Progestin and Thrombin Regulate Tissue Factor Expression in Human Term Decidual Cells J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 2164 - 2170. [Abstract] [Full Text] [PDF]

				N. Mackman On the Trail of Microparticles Circ. Res., April 24, 2009; 104(8): 925 - 927. [Full Text] [PDF]

				P. Redecha, N. van Rooijen, D. Torry, and G. Girardi Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury Blood, April 23, 2009; 113(17): 4101 - 4109. [Abstract] [Full Text] [PDF]

				F. A. Bozza, A. M. Shah, A. S. Weyrich, and G. A. Zimmerman Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 123 - 134. [Abstract] [Full Text] [PDF]

				E. I. Tucker, U. M. Marzec, T. C. White, S. Hurst, S. Rugonyi, O. J. T. McCarty, D. Gailani, A. Gruber, and S. R. Hanson Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI Blood, January 22, 2009; 113(4): 936 - 944. [Abstract] [Full Text] [PDF]

				H. Yoshida, J. Russell, and D. N. Granger Thrombin mediates the extraintestinal thrombosis associated with experimental colitis Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G904 - G908. [Abstract] [Full Text] [PDF]

				J. Yu, L. May, C. Milsom, G. M. Anderson, J. I. Weitz, J. P. Luyendyk, G. Broze, N. Mackman, and J. Rak Contribution of Host-Derived Tissue Factor to Tumor Neovascularization Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1975 - 1981. [Abstract] [Full Text] [PDF]

				G. T. Roberts, H. Ghebeh, M. A. Chishti, F. Al-Mohanna, R. El-Sayed, F. Al-Mohanna, and A. Bouchama Microvascular Injury, Thrombosis, Inflammation, and Apoptosis in the Pathogenesis of Heatstroke: A Study in Baboon Model Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1130 - 1136. [Abstract] [Full Text] [PDF]

				M. Brambilla, M. Camera, D. Colnago, G. Marenzi, M. De Metrio, P. L. Giesen, A. Balduini, F. Veglia, K. Gertow, P. Biglioli, et al. Tissue Factor in Patients With Acute Coronary Syndromes: Expression in Platelets, Leukocytes, and Platelet-Leukocyte Aggregates Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 947 - 953. [Abstract] [Full Text] [PDF]