Anti-idiotype monoclonal antibodies against emicizumab enable accurate procoagulant and anticoagulant assays, irrespective of the test base, in the presence of emicizumab.
Haemophilia
; 29(1): 329-335, 2023 Jan.
Article
em En
| MEDLINE
| ID: mdl-36137299
ABSTRACT
INTRODUCTION:
Emicizumab markedly shortens the activated partial thromboplastin time (aPTT), resulting in inaccurate measurements of procoagulant and anticoagulant factor activities. We have recently reported that mixtures of two different anti-idiotype monoclonal antibodies against emicizumab (anti-emicizumab-mAbs) allow measurement of factor (F)VIII activity (FVIIIC) and FVIII inhibitor in emicizumab-containing plasmas. It is unknown whether anti-emicizumab mAbs can work for other aPTT-based procoagulant and anticoagulant assays.AIM:
To investigate whether anti-emicizumab mAbs were measured by all of the aPTT-based assays tested.METHODS:
Two anti-emicizumab-mAbs (300 µg/mL each) were preincubated with emicizumab (200 µg/mL)-spiked FVIII-deficient plasma; we then measured FVIIIC, FIXC, FXIC, FXIIC, protein (P)CC, PSC, global PC-FV (aPTT-based), and prothrombin time (PT), diluted Russel's viper venom time (dRVVT), chromogenic-based FVIIIC, FIXC and PCC (non-aPTT-based). Emicizumab (100 µg/mL)-spiked haemophilia (H)A plasmas from patients (n = 23) were also measured.RESULTS:
Emicizumab shortened the clotting time in all aPTT-based assays, resulting in high levels of FVIIIC, FIXC, FXIC and FXIIC; low levels of PCC and PSC; and false-positive results for activated PC resistance. The addition of anti-emicizumab-mAbs to emicizumab-added plasma restored all factors to the initial levels without emicizumab. Chromogenic FVIIIC measurement by human FIXa/FX was affected by emicizumab, but anti-emicizumab mAbs cancelled this effect. PT-based assays and dRVVT, chromogenic FIXC and PCC assays showed no effect with emicizumab. Twenty-three plasma samples from HA patients also showed similar patterns.CONCLUSION:
Anti-emicizumab mAbs in vitro could cancel the effect of emicizumab, irrespective of the test base, resulting in accurate measurements of procoagulant and anticoagulant factor activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Biespecíficos
/
Hemofilia A
Limite:
Humans
Idioma:
En
Revista:
Haemophilia
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão