{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:17Z","timestamp":1790837057466,"version":"4.1.0"},"reference-count":44,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n            Background\u2003Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that targets factor Xa (FXa) in the presence of protein Z (PZ), and factor XIa (FXIa). In factor-VIII-deficient mice, PZ or ZPI gene knock-out mitigates the bleeding phenotype, and pharmacological inhibition of PZ enhances thrombin generation in plasma from patients with hemophilia.<\/jats:p><jats:p>\n            Aims\u2003To develop a single-domain antibody (sdAb) directed against ZPI to inhibit its anticoagulant activity.<\/jats:p><jats:p>\n            Methods\u2003We screened for anti-ZPI sdAbs in a llama-derived phage display immune library of sdAbs. The sdAbs that bound ZPI were produced and purified for characterization. The binding of sdAbs to ZPI or other serpins was evaluated using ELISAs, and ZPI inhibition was measured in an anti-FXa or anti-FXIa chromogenic assay. The sdAbs's procoagulant activity was assessed in a thrombin generation assay in normal plasma, factor VIII- and FXI-deficient plasma.<\/jats:p><jats:p>\n            Results\u2003Of the four sdAbs found to bind to ZPI, one (referred to as ZPI-sdAb2) dose-dependently inhibited ZPI's anti-FXa and anti-FXIa activities with a mean half-maximal inhibitory concentration of 1.8 and 1.3 \u00b5M, respectively. ZPI-sdAb2 did not cross-react with other plasma serpins, such as antithrombin and \u03b11-antitrypsin. ZPI-sdAb2 induced a significant increase in thrombin generation in plasma samples from healthy donors, patients with severe hemophilia A, and patients with FXI deficiency.<\/jats:p><jats:p>\n            Conclusion\u2003ZPI-sdAb2 is the first specific, direct ZPI inhibitor found to exhibit procoagulant activity in plasma. This sdAb might have potential as a treatment for hemophilia or other bleeding disorders.<\/jats:p>","DOI":"10.1055\/a-2373-2829","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T23:03:30Z","timestamp":1721948610000},"page":"207-217","source":"Crossref","is-referenced-by-count":5,"title":["An Inhibitory Single-Domain Antibody against Protein Z-Dependent Protease Inhibitor Promotes Thrombin Generation in Severe Hemophilia A and FXI Deficiency"],"prefix":"10.1055","volume":"125","author":[{"given":"Claire","family":"Auditeau","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Necker Enfants Malades, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris, 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Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Blandini\u00e8res","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Laboratoire d'H\u00e9matologie Biologique, H\u00f4pital Bic\u00eatre, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Facult\u00e9 de m\u00e9decine, universit\u00e9 Paris Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Rep\u00e9rant","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadyo","family":"Daram\u00e9","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile V.","family":"Denis","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lenting","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Borgel","sequence":"additional","affiliation":[{"name":"INSERM, H\u00e9mostase inflammation thrombose HITh U1176, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Necker Enfants Malades, Assistance 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