Factor IX assay discrepancies in the setting of liver gene therapy using a hyperfunctional variant factor IX-Padua.
J Thromb Haemost
; 19(5): 1212-1218, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33636038
ABSTRACT
BACKGROUND:
Limited information exists regarding the factor IX (FIX) coagulant activity (FIXC) measured by different assays following FIX-Padua gene therapy.OBJECTIVE:
Assess for the first time FIXC in five commonly used coagulation assays in plasma samples from hemophilia B subjects receiving FIX-Padua gene transfer.METHODS:
FIXC was compared between central (n = 1) and local laboratories (n = 5) in the study, and across four commonly used FIXC one-stage assays and one FIXC chromogenic assay. For comparison, samples of pooled congenital FIX-deficient plasma spiked with purified recombinant human FIX (rHFIX)-Padua protein or rHFIX (nonacog alfa) to obtain FIXC concentrations from ~20% to ~40% were tested.RESULTS:
FIXC results at local laboratories strongly correlated with central laboratory results. However, absolute values at the central laboratory were consistently lower than those at local laboratories. Across five different FIXC assays, a consistent pattern of FIXC was observed for subjects receiving fidanacogene elaparvovec-expressed gene transfer. Use of Actin FSL activated partial thromboplastin time (APTT) reagent in the central laboratory resulted in lower FIXC values compared with other APTT reagents tested. The chromogenic assay determined lower FIXC than any of the one-stage assays. The rHFIX-Padua protein-spiked samples showed similar results. In contrast, FIXC results for rHFIX-nonacog alfa measured within 25% of expected for all one-stage assays and below 25% in the chromogenic assay.CONCLUSIONS:
Assay-based differences in FIXC were observed for fidanacogene elaparvovec transgene product and rHFIX-Padua protein, suggesting the variable FIXC determined with different assay reagents is inherent to the FIX-Padua protein and is not specific to gene therapy-derived FIX-Padua.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor IX
/
Hemofilia B
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos