Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A.
assay discrepancies
coagulation biomarkers
lonoctocog alfa
octocog alfa
thrombin generation
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
20 Aug 2024
20 Aug 2024
Historique:
revised:
02
08
2024
received:
03
06
2024
accepted:
08
08
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
20
8
2024
Statut:
aheadofprint
Résumé
Lonoctocog alfa is a single-chain factor VIII (FVIII) molecule with high binding affinity to von-Willebrand-factor. While it is well known that its plasma activity is underestimated by one-stage clotting assays (OSCA), there is a lack of knowledge on the post-infusion performance of lonoctocog alfa in global coagulation assays or its potential impact on the haemostatic balance in vivo. To characterize lonoctocog alfa versus octocog alfa in pre- and post-infusion samples obtained from patients undergoing repeated investigation of incremental recovery (IR). Eighteen patients with severe haemophilia A (lonoctocog alfa: 10, octocog alfa: 8) were included. A panel of factor-specific and global coagulation assays was applied, comprising a FVIII OSCA, two FVIII chromogenic substrate assays (CSA), rotational thrombelastography and thrombin generation (TG). Potential activation of coagulation was assessed by measuring plasma thrombin markers and levels of activated protein C. Comparable IRs were found for lonoctocog alfa and octocog alfa (2.36 [IU/dL]/[IU/kg] vs. 2.55 [IU/dL]/[IU/kg], respectively). Lonoctocog alfa activities were found to be underestimated by the FVIII OSCA while also the two FVIII CSAs showed statistically significant assay discrepancies on lonoctocog alfa. Effects of both FVIII products on rotational thrombelastography were less distinct than those on TG parameters. No elevated pre- or significantly shifting post-infusion plasma levels of coagulation biomarkers were detected. Lonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CSL Behring
Informations de copyright
© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.
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