The Role of Tissue Factor and Factor VIIa in Hemostasis

Tissue factor (TF) is a transmembrane receptor for Factor VII/VIIa (FVII/VIIa). It is constitutively expressed by cells surrounding blood vessels. The endothelium physically separates this potent “activator” from its circulating ligand FVII/FVIIa and prevents inappropriate activation of the clotting...

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Veröffentlicht in:Anesthesia and analgesia 2009-05, Vol.108 (5), p.1447-1452
1. Verfasser: Mackman, Nigel
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description Tissue factor (TF) is a transmembrane receptor for Factor VII/VIIa (FVII/VIIa). It is constitutively expressed by cells surrounding blood vessels. The endothelium physically separates this potent “activator” from its circulating ligand FVII/FVIIa and prevents inappropriate activation of the clotting cascade. Breakage of the endothelial barrier leads to exposure of extravascular TF and rapid activation of the clotting cascade. TF is also expressed in certain tissues, such as the heart and brain, and provides additional hemostatic protection to these tissues. Small amounts of TF are also present in blood in the form of microparticles, which are small membrane vesicles derived from activated and apoptotic cells. Levels of microparticle TF increase in a variety of diseases, such as sepsis and cancer, and this so-called “blood-borne” TF may contribute to thrombosis associated with these diseases. Recombinant FVIIa has been developed as an effective hemostatic drug for the treatment of hemophilia patients with inhibitory antibodies. In addition, it is used for patients with bleeding that do not respond to conventional therapy. However, the mechanism by which recombinant FVIIa restores hemostasis has not been clearly defined. In conclusion, the TF:FVIIa complex is essential for hemostasis and recombinant FVIIa is an effective hemostatic drug.
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Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell-Derived Microparticles - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Factor VIIa - adverse effects</subject><subject>Factor VIIa - metabolism</subject><subject>Factor VIIa - therapeutic use</subject><subject>Hemophilia A - blood</subject><subject>Hemophilia A - drug therapy</subject><subject>Hemostasis - drug effects</subject><subject>Hemostatics - adverse effects</subject><subject>Hemostatics - therapeutic use</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Recombinant Proteins - adverse effects</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Thromboplastin - metabolism</subject><subject>Thrombosis - chemically induced</subject><issn>0003-2999</issn><issn>1526-7598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUUtLw0AQXkTRWv0HIrl4jO4zm70IUqwWCoJUr8tkM2ujaVJ2U4v_3pTW51xmhvke8A0hZ4xeMs7EFTR4SQvKBAqWM1M4LNgeGTDFs1Qrk--TAaVUpNwYc0SOY3ztV0bz7JAcMSM072kDomdzTB7bGpPWJ7MqxhUmY3BdGxJoyq_xeTKBpGqSe1y0sYNYxRNy4KGOeLrrQ_I0vp2N7tPpw91kdDNNnZJapgVVuqCoBPgcnEIA5lDrLCuk5K40HiGnJldeYuE9QxCOKVmC52XGNXgxJNdb3eWqWGDpsOkC1HYZqgWED9tCZf9emmpuX9p3y3ORayZ6AbkVcKGNMaD_5jJqN0HaPkj7P8iedv7b94e0S64HXOwAEB3UPkDjqviN40xSI3X2479u6w5DfKtXawx2jlB3c0s3pYRJOaWGqn5JN1-S4hMMSY5i</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Mackman, Nigel</creator><general>International Anesthesia Research Society</general><general>Lippincott Williams &amp; Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20090501</creationdate><title>The Role of Tissue Factor and Factor VIIa in Hemostasis</title><author>Mackman, Nigel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5474-b057b0e53af8ac5eaa1ce7766b442cd9fea80985f4ebff1ea3c154daf2d627af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Anesthesia</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell-Derived Microparticles - metabolism</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Factor VIIa - adverse effects</topic><topic>Factor VIIa - metabolism</topic><topic>Factor VIIa - therapeutic use</topic><topic>Hemophilia A - blood</topic><topic>Hemophilia A - drug therapy</topic><topic>Hemostasis - drug effects</topic><topic>Hemostatics - adverse effects</topic><topic>Hemostatics - therapeutic use</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Recombinant Proteins - adverse effects</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Thromboplastin - metabolism</topic><topic>Thrombosis - chemically induced</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mackman, Nigel</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Anesthesia and analgesia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mackman, Nigel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of Tissue Factor and Factor VIIa in Hemostasis</atitle><jtitle>Anesthesia and analgesia</jtitle><addtitle>Anesth Analg</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>108</volume><issue>5</issue><spage>1447</spage><epage>1452</epage><pages>1447-1452</pages><issn>0003-2999</issn><eissn>1526-7598</eissn><coden>AACRAT</coden><abstract>Tissue factor (TF) is a transmembrane receptor for Factor VII/VIIa (FVII/VIIa). It is constitutively expressed by cells surrounding blood vessels. The endothelium physically separates this potent “activator” from its circulating ligand FVII/FVIIa and prevents inappropriate activation of the clotting cascade. Breakage of the endothelial barrier leads to exposure of extravascular TF and rapid activation of the clotting cascade. TF is also expressed in certain tissues, such as the heart and brain, and provides additional hemostatic protection to these tissues. Small amounts of TF are also present in blood in the form of microparticles, which are small membrane vesicles derived from activated and apoptotic cells. Levels of microparticle TF increase in a variety of diseases, such as sepsis and cancer, and this so-called “blood-borne” TF may contribute to thrombosis associated with these diseases. Recombinant FVIIa has been developed as an effective hemostatic drug for the treatment of hemophilia patients with inhibitory antibodies. In addition, it is used for patients with bleeding that do not respond to conventional therapy. However, the mechanism by which recombinant FVIIa restores hemostasis has not been clearly defined. In conclusion, the TF:FVIIa complex is essential for hemostasis and recombinant FVIIa is an effective hemostatic drug.</abstract><cop>Hagerstown, MD</cop><pub>International Anesthesia Research Society</pub><pmid>19372318</pmid><doi>10.1213/ane.0b013e31819bceb1</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Cell-Derived Microparticles - metabolism
Endothelium, Vascular - metabolism
Factor VIIa - adverse effects
Factor VIIa - metabolism
Factor VIIa - therapeutic use
Hemophilia A - blood
Hemophilia A - drug therapy
Hemostasis - drug effects
Hemostatics - adverse effects
Hemostatics - therapeutic use
Humans
Medical sciences
Recombinant Proteins - adverse effects
Recombinant Proteins - therapeutic use
Thromboplastin - metabolism
Thrombosis - chemically induced
title The Role of Tissue Factor and Factor VIIa in Hemostasis
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