<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-00813345</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-25T01:06:24+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Gla-domainless factor Xa: molecular bait to bypass a blocked tenase complex.</title>
            <author role="aut">
              <persName>
                <forename type="first">Raphaël</forename>
                <surname>Marlu</surname>
              </persName>
              <idno type="halauthorid">391802-0</idno>
              <affiliation ref="#struct-396554"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Benoît</forename>
                <surname>Polack</surname>
              </persName>
              <email type="md5">57561dd4fe217a1caf2697ee917e4754</email>
              <email type="domain">chu-grenoble.fr</email>
              <idno type="idhal" notation="numeric">839736</idno>
              <idno type="halauthorid" notation="string">366555-839736</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-1697-6249</idno>
              <idno type="IDREF">https://www.idref.fr/059672048</idno>
              <idno type="VIAF">https://viaf.org/viaf/201988847</idno>
              <idno type="ISNI">http://isni.org/isni/0000000357994889</idno>
              <affiliation ref="#struct-396554"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Marie-Claire</forename>
                <surname>Dagher</surname>
              </persName>
              <email type="md5">16a92a66fdebde7a6e37680303039cc5</email>
              <email type="domain">ibs.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2013-04-15 14:41:37</date>
              <date type="whenModified">2025-09-27 19:00:34</date>
              <date type="whenReleased">2013-04-15 14:41:37</date>
              <date type="whenProduced">2012-08</date>
              <ref type="externalLink" target="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409813"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="140374">
                <persName>
                  <forename>Marie-Claire</forename>
                  <surname>Dagher</surname>
                </persName>
                <email type="md5">16a92a66fdebde7a6e37680303039cc5</email>
                <email type="domain">ibs.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-00813345</idno>
            <idno type="halUri">https://hal.science/hal-00813345</idno>
            <idno type="halBibtex">marlu:hal-00813345</idno>
            <idno type="halRefHtml">&lt;i&gt;Haematologica&lt;/i&gt;, 2012, 97 (8), pp.1165-72. &lt;a target="_blank" href="https://dx.doi.org/10.3324/haematol.2011.055699"&gt;&amp;#x27E8;10.3324/haematol.2011.055699&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Haematologica, 2012, 97 (8), pp.1165-72. &amp;#x27E8;10.3324/haematol.2011.055699&amp;#x27E9;</idno>
            <availability status="restricted"/>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="UGA">HAL Grenoble Alpes</idno>
            <idno type="stamp" n="IMAG">IMAG</idno>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="UNIV-GRENOBLE1">Université Joseph Fourier - Grenoble I</idno>
            <idno type="stamp" n="INPG">Institut polytechnique de Grenoble</idno>
            <idno type="stamp" n="TIMC-IMAG">TIMC</idno>
            <idno type="stamp" n="TIMC-IMAG-THEREX" corresp="TIMC-IMAG">TheREx : Thérapeutique Recombinante Expérimentale</idno>
            <idno type="stamp" n="UNIV-LYON">Université de Lyon</idno>
            <idno type="stamp" n="TEST-UGA">TEST-UGA</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Gla-domainless factor Xa: molecular bait to bypass a blocked tenase complex.</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Raphaël</forename>
                    <surname>Marlu</surname>
                  </persName>
                  <idno type="halauthorid">391802-0</idno>
                  <affiliation ref="#struct-396554"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Benoît</forename>
                    <surname>Polack</surname>
                  </persName>
                  <email type="md5">57561dd4fe217a1caf2697ee917e4754</email>
                  <email type="domain">chu-grenoble.fr</email>
                  <idno type="idhal" notation="numeric">839736</idno>
                  <idno type="halauthorid" notation="string">366555-839736</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-1697-6249</idno>
                  <idno type="IDREF">https://www.idref.fr/059672048</idno>
                  <idno type="VIAF">https://viaf.org/viaf/201988847</idno>
                  <idno type="ISNI">http://isni.org/isni/0000000357994889</idno>
                  <affiliation ref="#struct-396554"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">22186</idno>
                <idno type="issn">0390-6078</idno>
                <idno type="eissn">1592-8721</idno>
                <title level="j">Haematologica</title>
                <imprint>
                  <publisher>Ferrata Storti Foundation</publisher>
                  <biblScope unit="volume">97</biblScope>
                  <biblScope unit="issue">8</biblScope>
                  <biblScope unit="pp">1165-72</biblScope>
                  <date type="datePub">2012-08</date>
                  <date type="dateEpub">2012-04-04</date>
                </imprint>
              </monogr>
              <idno type="doi">10.3324/haematol.2011.055699</idno>
              <idno type="pubmed">22491732</idno>
              <idno type="pubmedcentral">PMC3409813</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <classCode scheme="mesh">Antibodies</classCode>
              <classCode scheme="mesh">Antithrombins</classCode>
              <classCode scheme="mesh">Lipoproteins</classCode>
              <classCode scheme="mesh">Multiprotein Complexes</classCode>
              <classCode scheme="mesh">Neoplasm Proteins</classCode>
              <classCode scheme="mesh">Protein Binding</classCode>
              <classCode scheme="mesh">Signal Transduction</classCode>
              <classCode scheme="mesh">Thrombin</classCode>
              <classCode scheme="mesh">Cysteine Endopeptidases</classCode>
              <classCode scheme="mesh">Factor Xa</classCode>
              <classCode scheme="mesh">Half-Life</classCode>
              <classCode scheme="mesh">Hemophilia A</classCode>
              <classCode scheme="mesh">Humans</classCode>
              <classCode scheme="halDomain" n="sdv.imm.ii">Life Sciences [q-bio]/Immunology/Innate immunity</classCode>
              <classCode scheme="halDomain" n="sdv.mhep">Life Sciences [q-bio]/Human health and pathology</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.hem">Life Sciences [q-bio]/Human health and pathology/Hematology</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>BACKGROUND: Hemophilia is caused by deficiencies in coagulation factor VIII or IX, resulting in direct blockade of the intrinsic tenase complex and indirect blockade of the extrinsic tenase complex which is rapidly inhibited upon binding of factor Xa to tissue factor pathway inhibitor. We evaluated the ability of Gla-domainless factor Xa, a truncated form of factor Xa devoid of procoagulant properties, to bind to tissue factor pathway inhibitor and to alleviate the physiological inhibition of the extrinsic tenase. DESIGN AND METHODS: Using a thrombin generation assay triggered by a low concentration of tissue factor, we evaluated the ability of Gla-domainless factor Xa to restore blood coagulation in plasma from hemophilia A and B patients without and with inhibitors. We then compared its efficacy to generate thrombin to depletion of antithrombin or tissue factor pathway inhibitor by specific antibodies. Finally, we compared the kinetics of neutralization of factor Xa and Gla-domainless factor Xa by antithrombin and tissue factor pathway inhibitor. RESULTS: Gla-domainless factor Xa was able to restore thrombin generation in plasma samples from hemophiliacs. This effect was observed for plasma from hemophilia A patients without or with inhibitors and for plasma from hemophilia B patients. Gla-domainless factor Xa had a lower affinity than factor Xa for tissue factor pathway inhibitor whereas the affinities of both proteins for antithrombin were similar. Finally, despite a short half-life in plasma, the effect of Gla-domainless factor Xa on thrombin generation was sustained for at least 1 hour. CONCLUSIONS: As Gla-domainless factor Xa was able to restore thrombin generation in plasma from hemophilia patients, our results suggest that it may be an effective alternative to current treatments for hemophilia with or without an inhibitor.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="researchteam" xml:id="struct-396554" status="OLD">
          <orgName>Thérapeutique Recombinante Expérimentale</orgName>
          <orgName type="acronym">TIMC-IMAG-TheREx</orgName>
          <date type="end">2015-12-31</date>
          <desc>
            <address>
              <addrLine>Domaine de la Merci, 37006 La Tronche, France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www-timc.imag.fr/THEREX</ref>
          </desc>
          <listRelation>
            <relation active="#struct-707" type="direct"/>
            <relation active="#struct-51016" type="indirect"/>
            <relation active="#struct-89889" type="indirect"/>
            <relation active="#struct-301767" type="indirect"/>
            <relation name="UMR5525" active="#struct-441569" type="indirect"/>
          </listRelation>
        </org>
        <org type="laboratory" xml:id="struct-707" status="OLD">
          <idno type="IdRef">14728936X</idno>
          <idno type="ISNI">0000 0004 4687 1979</idno>
          <idno type="RNSR">199511969L</idno>
          <idno type="ROR">https://ror.org/03985kf35</idno>
          <orgName>Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525</orgName>
          <orgName type="acronym">TIMC-IMAG</orgName>
          <date type="start">1993-01-01</date>
          <date type="end">2015-12-31</date>
          <desc>
            <address>
              <addrLine>Domaine de la Merci, 38706 La Tronche, France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www-timc.imag.fr</ref>
          </desc>
          <listRelation>
            <relation active="#struct-51016" type="direct"/>
            <relation active="#struct-89889" type="direct"/>
            <relation active="#struct-301767" type="direct"/>
            <relation name="UMR5525" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-51016" status="OLD">
          <idno type="IdRef">026404796</idno>
          <idno type="ROR">https://ror.org/02aj0kh94</idno>
          <orgName>Université Joseph Fourier - Grenoble 1</orgName>
          <orgName type="acronym">UJF</orgName>
          <date type="end">2015-12-31</date>
          <desc>
            <address>
              <addrLine>BP 53 - 38041 Grenoble Cedex 9</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.ujf-grenoble.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-89889" status="OLD">
          <idno type="IdRef">026388804</idno>
          <idno type="ROR">https://ror.org/05sbt2524</idno>
          <orgName>Institut polytechnique de Grenoble - Grenoble Institute of Technology</orgName>
          <orgName type="acronym">Grenoble INP</orgName>
          <date type="start">2007-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>46 avenue Félix Viallet 38031 Grenoble Cedex 1</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.grenoble-inp.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-301767" status="VALID">
          <idno type="ROR">https://ror.org/01c7wz417</idno>
          <orgName>VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement</orgName>
          <orgName type="acronym">VAS</orgName>
          <date type="start">2010-01-01</date>
          <desc>
            <address>
              <addrLine>Université de Lyon, VetAgro Sup, 69280 Marcy l'Etoile (campus vétérinaire); Université de Clermont, VetAgro Sup, 63370 Lempdes (campus agronomique)</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.vetagro-sup.fr/</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>