Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma
Author:
Tripodi Armando12, Chantarangkul Veena12, Novembrino Cristina1, Scalambrino Erica13, Boscolo-Anzoletti Massimo1, Clerici Marigrazia1, Rossi Federica1, Peyvandi Flora123
Affiliation:
1. Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano , Milan , Italy 2. Fondazione Luigi Villa , Milan , Italy 3. Department of Pathophysiology and Transplantation, Università degli Studi di Milano , Milan , Italy
Abstract
Abstract
Objectives
Emicizumab, a monoclonal antibody mimicking the function of factor (F) VIII in the activation of FX by FIXa, is widely used for prophylaxis in hemophilia patients with or without inhibitors to FVIII. Although it is administered at fixed dose, its measurement could be occasionally required. In principle, the emicizumab procoagulant effect could be assessed by the one-stage assay (OSA) currently used to measure FVIII. However, the OSA for FVIII presents with limitations. Furthermore, owing to its potent FVIII-like activity, emicizumab interferes with the measurement of the inhibitor to FVIII, which is often needed in patients on emicizumab.
Methods
We prepared test samples by spiking a FVIII-deficient plasma with graded amounts of emicizumab. We modified the OSA for FVIII and tested plasma samples for emicizumab concentrations. Furthermore the chromogenic assay (CA) for FVIII with bovine reagents was used to assess for the FVIII inhibitor in patients on emicizumab.
Results
Slight modification of the OSA for FVIII (i.e., higher test plasma dilution and longer coagulometer acquisition time) made the regular OSA as a reliable laboratory tool to measure emicizumab concentration as shown by the identity of the regression (observed vs. expected) lines. Furthermore, the inhibitors to FVIII in patients on emicizumab, which were negative when measured by the regular Bethesda assay, were reliably measured by the CA assay employing bovine reagents.
Conclusions
The methods currently used to measure FVIII can be easily modified to make the general clinical laboratory able to assist clinicians when dealing with patients on emicizumab.
Publisher
Walter de Gruyter GmbH
Subject
Biochemistry, medical,Clinical Biochemistry,General Medicine
Reference15 articles.
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