Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors.
APTT
chromogenic
emicizumab
factor VIII
haemophilia A
one-stage
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:
May 2020
May 2020
Historique:
received:
04
11
2019
revised:
26
02
2020
accepted:
17
03
2020
pubmed:
7
4
2020
medline:
15
12
2020
entrez:
7
4
2020
Statut:
ppublish
Résumé
Emicizumab (Hemlibra, Roche-Chugai) is a recombinant humanized bispecific IgG4 antibody which mimics some of the actions of activated factor VIII (FVIIIa) by binding to factor X (FX) and activated factor IX (FIXa) to activate FX. To evaluate the effect of emicizumab on the APTT, standard one-stage APTT-based FVIII activity assay (sOSA) using plasma calibrators, modified OSA (mOSA) using r APTT in spiked plasma was performed with 13 APTT reagents and in SHA patients with 5 reagents. OSA in spiked plasma was performed with 9 APTT reagents, 7 APTT reagents were used for OSA in SHA patients and six chromogenic substrate assays (CSA) were performed. In SHA, APTTs normalized after the first dose of emicizumab. At weeks 32/36 of treatment, the mean sOSA FVIII:C ranged from 2.47 IU/mL (Synthasil) to greater than 7.00 IU/mL with all other reagents. mOSA ranged from 59.8 µg/mL (Synthasil) to 74.5 µg/mL (APTT SP). Bovine CSA did not recover any FVIII:C activity. Hyphen Biomed human CSA, demonstrated FVIII activity when calibrated against a plasma calibrator. The APTT was significantly shortened in the presence of emicizumab. sOSA FVIII:C levels were erroneously high, and it is not recommended that these be performed. Quantification of emicizumab concentration was possible by mOSA. Human CSA was sensitive to emicizumab and surrogate FVIII:C activity could be determined. Bovine CSA were insensitive to emicizumab and could not be used to quantify emicizumab concentration.
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
Hemostatics
0
emicizumab
7NL2E3F6K3
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
536-542Subventions
Organisme : Roche
Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
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