Intrinsic pathway of coagulation and arterial thrombosis

被引:216
作者
Gailani, David
Renne, Thomas
机构
[1] Vanderbilt Univ, Dept Pathol, Nashville, TN USA
[2] Vanderbilt Univ, Dept Med, Nashville, TN USA
[3] Univ Wurzburg, Inst Clin Biochem & Pathobiochem, Wurzburg, Germany
关键词
intrinsic pathways; coagulation; arterial thrombosis;
D O I
10.1161/ATVBAHA.107.155952
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2507 / 2513
页数:7
相关论文
共 89 条
[51]  
MCFARLANE RG, 1977, BRIT MED BULL, V33, P183
[52]  
MEIJERS J, 2000, NEW ENGL J MED, V342, P29
[53]   High levels of coagulation factor XI as a risk factor for venous thrombosis. [J].
Meijers, JCM ;
Tekelenburg, WLH ;
Bouma, BN ;
Bertina, RM ;
Rosendaal, FR .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (10) :696-701
[54]   Tissue factor: A key molecule in hemostatic and nonhemostatic systems [J].
Morrissey, JH .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2004, 79 (02) :103-108
[55]  
Muchitsch EM, 1999, THROMB HAEMOSTASIS, V82, P1371
[56]  
NAITO K, 1991, J BIOL CHEM, V266, P7353
[57]   ACTIVATION OF FACTOR-IX BY REACTION-PRODUCT OF TISSUE FACTOR AND FACTOR-VII-ADDITIONAL PATHWAY FOR INITIATING BLOOD-COAGULATION [J].
OSTERUD, B ;
RAPAPORT, SI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (12) :5260-5264
[58]   Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo [J].
Pauer, HU ;
Renné, T ;
Hemmerlein, B ;
Legler, T ;
Fritzlar, S ;
Adham, I ;
Müller-Esterl, W ;
Emons, G ;
Sancken, U ;
Engels, W ;
Burfeind, P .
THROMBOSIS AND HAEMOSTASIS, 2004, 92 (03) :503-508
[59]  
RADCLIFFE R, 1977, BLOOD, V50, P611
[60]  
RAPAPORT SI, 1995, THROMB HAEMOSTASIS, V74, P7