Multicenter evaluation of the hemostatic activity of emicizumab in patients with severe hemophilia A.
J Thromb Haemost
; 22(7): 1857-1866, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38583717
ABSTRACT
BACKGROUND:
Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis, and no laboratory assay has been validated to evaluate the hemostatic activity of emicizumab.OBJECTIVES:
The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab. The correlation between TGA and the methods used to measure emicizumab blood concentration was evaluated in this study.METHODS:
TGA was modified by the use of a trigger reagent combining a very low concentration of tissue factor and activated factor (F)XI. Emicizumab quantification was performed by 3methods:
the modified 1-step FVIII assay and 2 methods based on liquid chromatography and mass spectrometry (LC-MS).RESULTS:
Using tissue factor/activated FXI-triggered TGA and platelet-poor plasma, a relationship was observed between the area under the thrombin generation curve (endogenous thrombin potential [ETP]) and the clinical response of patients to emicizumab. The ultrastructure of fibrin clots was consistent with ETP results and showed that emicizumab had a hemostatic activity equivalent to 20 to 30 IU/dL of FVIII. Finally, pharmacokinetic/pharmacodynamic analyses showed no correlation between ETP and LC-MS nor with modified 1-stage FVIII assay, but a statistically significant correlation between the LC-MS methods and the time-to-peak results of the TGA.CONCLUSION:
Using a modified TGA, this study showed that patients who experienced breakthrough bleeds while on emicizumab had a lower thrombin-generating capacity compared with others with good clinical response to emicizumab.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombina
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Anticorpos Biespecíficos
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Anticorpos Monoclonais Humanizados
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Hemofilia A
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Hemostasia
Limite:
Adolescent
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Adult
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Child
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França