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Targeting Tissue Factor Pathway Inhibitor with concizumab to improve haemostasis in patients with Glanzmann thrombasthenia: an in vitro study.

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUBUT, Jade
dc.contributor.authorGOIN, Valérie
dc.contributor.authorDERRAY, Cloé
dc.contributor.authorHUGUENIN, Yoann
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorFIORE, Mathieu
dc.date.accessioned2024-07-05T13:54:59Z
dc.date.available2024-07-05T13:54:59Z
dc.date.issued2024-06-14
dc.identifier.issn1538-7836en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/200763
dc.description.abstractEnGlanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αβ integrin. Concizumab,a monoclonal antibody specific for Tissue Factor Pathway Inhibitor (TFPI), abolishes its anticoagulant effect. To evaluate the in vitro ability of concizumab to improve haemostasis in GT. The effects of concizumab were evaluated in whole blood or platelet-rich plasma (PRP) from GT patients (n=5-9) using a thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), a global fibrinolytic capacity assay and a flow-chamber assay (T-TAS). Washed platelets (WP) and 20 nM recombinant activated factor VIIa (rFVIIa) were included for comparison. The lag time in the TGA was significantly longer (+85%, p<0.0001) in GT patients than in controls. WP, rFVIIa and concizumab each significantly improved thrombin generation profiles. The ROTEM clotting time was significantly longer in GT patients than in controls (677 s vs 523 s; p=0.03). However, CT improved after adding WP, rFVIIa or concizumab. Under flow, occlusive thrombi were present in all healthy controls after 10 min, whereas platelet-fibrin depositions were not seen in GT patients. Sub-occlusive or occlusive thrombi formed when GT blood was mixed with WP, rFVIIa or concizumab. Clots in GT PRP were more susceptible to fibrinolysis and were improved by WP, rFVIIa or concizumab. Concizumab enhanced thrombin generation, decreased the ROTEM CT, improved thrombus formation under flow and reduced clot lysis. Our results demonstrate the potential of concizumab for subcutaneous prophylaxis in GT patients.
dc.language.isoENen_US
dc.subject.enGlanzmann thrombasthenia; Tissue Factor Pathway Inhibitor; activated recombinant factor VII; anti-α(IIb)β(3) isoantibodies; concizumab; platelet transfusion; thrombin generation
dc.title.enTargeting Tissue Factor Pathway Inhibitor with concizumab to improve haemostasis in patients with Glanzmann thrombasthenia: an in vitro study.
dc.title.alternativeJ Thromb Haemosten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.jtha.2024.05.033en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed38880178en_US
bordeaux.journalJournal of Thrombosis and Haemostasisen_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04637041
hal.version1
hal.date.transferred2024-07-05T13:55:01Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Journal%20of%20Thrombosis%20and%20Haemostasis&amp;rft.date=2024-06-14&amp;rft.eissn=1538-7836&amp;rft.issn=1538-7836&amp;rft.au=DUBUT,%20Jade&amp;GOIN,%20Val%C3%A9rie&amp;DERRAY,%20Clo%C3%A9&amp;HUGUENIN,%20Yoann&amp;FIORE,%20Mathieu&amp;rft.genre=article


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