Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.

Autor: Bravo MI; Bioscience Research Group, Grifols, Barcelona, Spain., Pérez A; Bioscience Research Group, Grifols, Barcelona, Spain., Raventós A; Bioscience Research Group, Grifols, Barcelona, Spain., Grancha S; Bioscience Research Group, Grifols, Barcelona, Spain., Jorquera JI; Bioscience Research Group, Grifols, Barcelona, Spain., Butta NV; Thrombosis and Haemostasis Unit - IdiPAZ, University Hospital La Paz, Madrid, Spain., Álvarez-Román MT; Thrombosis and Haemostasis Unit - IdiPAZ, University Hospital La Paz, Madrid, Spain., Costa M; Bioscience Research Group, Grifols, Barcelona, Spain., Willis T; Bioscience Research Group, Grifols, Raleigh, North Carolina, USA., Jiménez-Yuste V; Thrombosis and Haemostasis Unit - IdiPAZ, University Hospital La Paz, Madrid, Spain.; Medicine Department, Autonoma University of Madrid, Madrid, Spain.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2022 Sep; Vol. 28 (5), pp. 737-744. Date of Electronic Publication: 2022 Jun 02.
DOI: 10.1111/hae.14589
Abstrakt: Introduction: Presence of von Willebrand factor (VWF) in FVIII concentrates offers protection against neutralizing inhibitors in haemophilia A (HA). Whether this protection is more evident in plasma-derived (pd) FVIII/VWF or recombinant (r) FVIII concentrates remains controversial.
Aim: We investigated the protection exerted by VWF against FVIII inhibitors in an in vivo mouse model of HA exposed to pdFVIII/VWF or to various rFVIII concentrates.
Methods: Haemophilia A mice received the different FVIII concentrates after administration of vehicle or an inhibitory IgG purified from a commercial pool of HA plasma with inhibitors and FVIII:C recoveries were measured. Furthermore, using a novel clinically oriented ex vivo approach, Bethesda inhibitory activities (BU) of a commercial pool of HA plasma with inhibitors were assessed using normal plasma, or plasma from severe HA patients, without inhibitors, after treatment with the same concentrates.
Results: in vivo studies showed that pdFVIII/VWF offers markedly higher protection against inhibitors when compared with any of the FVIII products without VWF. More importantly, in the ex vivo studies, plasma from patients treated with pdFVIII/VWF showed higher protection against inhibitors (P values ranging .05-.001) in comparison with that observed in plasma from patients who received FVIII products without VWF, regardless of the type of product evaluated.
Conclusion: Data indicate that FVIII+VWF complexes assembled in the circulation after rFVIII infusion are not equivalent to the naturally formed complex in pdFVIII/VWF. Therefore, rFVIII infused into HA patients with inhibitors would be less protected by VWF than the FVIII in pdFVIII/VWF concentrates.
(© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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