on October 4, 2007
Published online before print October 4, 2007, doi: 10.1161/ATVBAHA.107.155952
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Submitted on May 7, 2007
Accepted on September 25, 2007
Intrinsic Pathway of Coagulation and Arterial Thrombosis
David Gailani * and 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.
* To whom correspondence should be addressed. E-mail: dave.gailani{at}vanderbilt.edu.
Abstract—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.
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