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Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma.
Clin Chem Lab Med. 2020 09 04; 59(2):365-371.CC

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.

Authors+Show Affiliations

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy. Fondazione Luigi Villa, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy. Fondazione Luigi Villa, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy.Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Milan, Italy. Fondazione Luigi Villa, Milan, Italy. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32892172

Citation

Tripodi, Armando, et al. "Emicizumab, the Factor VIII Mimetic Bi-specific Monoclonal Antibody and Its Measurement in Plasma." Clinical Chemistry and Laboratory Medicine, vol. 59, no. 2, 2020, pp. 365-371.
Tripodi A, Chantarangkul V, Novembrino C, et al. Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma. Clin Chem Lab Med. 2020;59(2):365-371.
Tripodi, A., Chantarangkul, V., Novembrino, C., Scalambrino, E., Boscolo-Anzoletti, M., Clerici, M., Rossi, F., & Peyvandi, F. (2020). Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma. Clinical Chemistry and Laboratory Medicine, 59(2), 365-371. https://doi.org/10.1515/cclm-2020-0696
Tripodi A, et al. Emicizumab, the Factor VIII Mimetic Bi-specific Monoclonal Antibody and Its Measurement in Plasma. Clin Chem Lab Med. 2020 09 4;59(2):365-371. PubMed PMID: 32892172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emicizumab, the factor VIII mimetic bi-specific monoclonal antibody and its measurement in plasma. AU - Tripodi,Armando, AU - Chantarangkul,Veena, AU - Novembrino,Cristina, AU - Scalambrino,Erica, AU - Boscolo-Anzoletti,Massimo, AU - Clerici,Marigrazia, AU - Rossi,Federica, AU - Peyvandi,Flora, Y1 - 2020/09/04/ PY - 2020/05/12/received PY - 2020/08/19/accepted PY - 2020/9/7/pubmed PY - 2021/9/22/medline PY - 2020/9/6/entrez KW - activated partial thromboplastin time KW - assay standardization KW - hemophilia KW - inhibitors SP - 365 EP - 371 JF - Clinical chemistry and laboratory medicine JO - Clin Chem Lab Med VL - 59 IS - 2 N2 - 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. SN - 1437-4331 UR - https://www.unboundmedicine.com/medline/citation/32892172/Emicizumab_the_factor_VIII_mimetic_bi_specific_monoclonal_antibody_and_its_measurement_in_plasma_ L2 - https://www.degruyter.com/document/doi/10.1515/cclm-2020-0696 DB - PRIME DP - Unbound Medicine ER -