This Article Full Text Full Text (PDF) All Versions of this Article: 27/12/2507    most recent ATVBAHA.107.155952v1 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 Gailani, D. Articles by Renné, T. Search for Related Content PubMed PubMed Citation Articles by Gailani, D. Articles by Renné, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2507.)
© 2007 American Heart Association, Inc.

Brief Reviews

Intrinsic Pathway of Coagulation and Arterial Thrombosis

David Gailani; Thomas Renné

From the Departments of Pathology and Medicine (D.G.), Vanderbilt University, Nashville, Tenn; and the Institute of Clinical Biochemistry and Pathobiochemistry (T.R.), University of Würzburg, Germany.

Correspondence to David Gailani, MD, Hematology/Oncology Division, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232-6307. E-mail dave.gailani{at}vanderbilt.edu or Thomas Renné, MD, PhD, Institute for Clinical Biochemistry and Pathobiochemistry, Julius-Maximilians-University Wüurzburg, Josef-Schneider Strasse 2, D-97080 Wüurzberg, Germany. E-mail thomas@renne.net

Formation of a fibrin clot is mediated by a group of tightly regulated plasma proteases and cofactors. While this system is essential for minimizing blood loss from an injured blood vessel (hemostasis), it also contributes to pathologic fibrin formation and platelet activation that may occlude vessels (thrombosis). Many antithrombotic drugs target key elements of the plasma coagulation mechanism such as thrombin and factor Xa, based on the premise that plasma elements contributing to thrombosis are primarily those involved in hemostasis. Recent studies with genetically altered mice raise questions about this paradigm. Deficiencies of the intrinsic pathway proteases factor XII and factor XI are not associated with abnormal hemostasis in mice, but impair formation of occlusive thrombi in arterial injury models, indicating that pathways not essential for hemostasis participate in arterial thrombosis. If factor XII or factor XI make similar contributions to thrombosis in humans, these proteases could be ideal targets for drugs to treat or prevent thromboembolic disease with minimal risk of therapy-associated bleeding.

Deficiencies of the plasma proteases factor XII and factor XI are not associated with abnormal hemostasis in mice but prevent thrombus formation in arterial injury models. If factor XII or factor XI make similar contributions to thrombosis in humans, they could be therapeutic targets to treat or prevent thromboembolic disease.

Key Words: Intrinsic pathways • coagulation • arterial thrombosis

This article has been cited by other articles:

				T. C. White-Adams, M. A. Berny, E. I. Tucker, J. M. Gertz, D. Gailani, R. T. Urbanus, P. G. de Groot, A. Gruber, and O. J.T. McCarty Identification of Coagulation Factor XI as a Ligand for Platelet Apolipoprotein E Receptor 2 (ApoER2) Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1602 - 1607. [Abstract] [Full Text] [PDF]

				J. C. M. Meijers Feedback controversy stops here Blood, July 9, 2009; 114(2): 235 - 235. [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]

				B. Furie and B. C. Furie Mechanisms of Thrombus Formation N. Engl. J. Med., August 28, 2008; 359(9): 938 - 949. [Full Text] [PDF]