{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T07:35:26Z","timestamp":1695540926398},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T00:00:00Z","timestamp":1408924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Sensitivity to <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> inhibitors of the native plasma\u2010derived (pd) <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> complex vs. the complexes formed after exogenous <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> infusion in the haemophilic patient has not been thoroughly studied. The role of <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> in the interaction of <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> with inhibitors was studied <jats:italic>in vitro<\/jats:italic> using different combinations of <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> concentrates. Normal plasma, pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> and isolated <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> (recombinant <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>, B\u2010domain deleted and pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>) were used. Titre (<jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>) was kinetically determined (up to 2\u00a0h) in serial dilutions of inhibitor IgG (purified from a pool of plasmas with inhibitors) mixed with <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> and then incubated with the different <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>. Inhibitor was also added to previously mixed <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>. Residual <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>:C was determined. <jats:styled-content style=\"fixed-case\">TGA<\/jats:styled-content> assays were performed with <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\u2010deficient plasma spiked with the <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> mixtures with\/without an <jats:styled-content style=\"fixed-case\">ESH<\/jats:styled-content>\u20108 antibody. Inhibitor titres for plasma and pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> were comparable at all time points. Titres for all concentrates of isolated <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> were significantly higher than those for plasma or pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> (1.4\u20131.9 fold) even after preincubation with <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>. At t\u00a0=\u00a00\u00a0h, titres for plasma or pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> were unquantifiable, but were detectable for isolated <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> (0.6\u20131.6 <jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>). In contrast to pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>, the decrease in thrombin generation parameters by isolated <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> in the presence of <jats:styled-content style=\"fixed-case\">ESH<\/jats:styled-content>\u20108 was significant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) even when previously combined with <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content>. In conclusion, <jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> protection against <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> inhibitor activity might be higher with native pd<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VWF<\/jats:styled-content> complex than with the corresponding compound formed from the isolated proteins. Bethesda assay titration using different <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> concentrates would be advisable to guide the treatment of inhibitor patients.<\/jats:p>","DOI":"10.1111\/hae.12494","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T08:28:33Z","timestamp":1408955313000},"page":"905-911","source":"Crossref","is-referenced-by-count":8,"title":["Native plasma\u2010derived <scp>FVIII<\/scp>\/<scp>VWF<\/scp> complex has lower sensitivity to <scp>FVIII<\/scp> inhibitors than the combination of isolated <scp>FVIII<\/scp> and <scp>VWF<\/scp> proteins. Impact on Bethesda assay titration of <scp>FVIII<\/scp> inhibitors"],"prefix":"10.1111","volume":"20","author":[{"given":"M. I.","family":"Bravo","sequence":"first","affiliation":[{"name":"Research and Development Area Instituto Grifols S.A. Parets del Vall\u00e8s Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Da Rocha\u2010Souto","sequence":"additional","affiliation":[{"name":"Research and Development Area Instituto Grifols S.A. Parets del Vall\u00e8s Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Grancha","sequence":"additional","affiliation":[{"name":"Research and Development Area Instituto Grifols S.A. Parets del Vall\u00e8s Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. I.","family":"Jorquera","sequence":"additional","affiliation":[{"name":"Research and Development Area Instituto Grifols S.A. 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