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 |
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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. |
doi_str_mv | 10.1213/ane.0b013e31819bceb1 |
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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.</description><identifier>ISSN: 0003-2999</identifier><identifier>EISSN: 1526-7598</identifier><identifier>DOI: 10.1213/ane.0b013e31819bceb1</identifier><identifier>PMID: 19372318</identifier><identifier>CODEN: AACRAT</identifier><language>eng</language><publisher>Hagerstown, MD: International Anesthesia Research Society</publisher><subject>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</subject><ispartof>Anesthesia and analgesia, 2009-05, Vol.108 (5), p.1447-1452</ispartof><rights>International Anesthesia Research Society</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 International Anesthesia Research Society 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5474-b057b0e53af8ac5eaa1ce7766b442cd9fea80985f4ebff1ea3c154daf2d627af3</citedby><cites>FETCH-LOGICAL-c5474-b057b0e53af8ac5eaa1ce7766b442cd9fea80985f4ebff1ea3c154daf2d627af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00000539-200905000-00014$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00000539-200905000-00014$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>230,315,782,786,887,4611,27931,27932,64673,65468</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21409476$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19372318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mackman, Nigel</creatorcontrib><title>The Role of Tissue Factor and Factor VIIa in Hemostasis</title><title>Anesthesia and analgesia</title><addtitle>Anesth Analg</addtitle><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.</description><subject>Anesthesia</subject><subject>Anesthesia. Intensive care medicine. Transfusions. 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 & 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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