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Thromb Haemost. 2019 Jun 16. doi: 10.1055/s-0039-1692427. [Epub ahead of print]

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A.

Author information

1
Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
2
Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany.
3
Department of Anaesthesiology, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.
4
Department of Transfusion Medicine, Cell Therapeutics and Hemostaseology, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.
5
Roche Pharma AG, Grenzach-Wyhlen, Germany.

Abstract

Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by deficiency of coagulation factor (F) VIII activity. One of the greatest complications in the treatment of HA is the development of neutralizing alloantibodies, known as FVIII inhibitors. HA patients who develop FVIII inhibitors have limited treatment options available to them and experience greater disease- and treatment-related burdens than HA patients without FVIII inhibitors. Emicizumab, a recently approved bispecific monoclonal antibody, mimics the function of FVIIIa by bridging FIXa and FX to restore effective hemostasis. Although emicizumab and FVIII show some functional similarities, several key differences influence the results of standard laboratory assays when conducted in the presence of emicizumab, and can result in a misleading interpretation of coagulation assays in emicizumab-treated patients. Here, we discuss current laboratory monitoring methods, including activated partial thromboplastin time, FVIII one-stage clotting assays, FVIII chromogenic assays, and global coagulations assays; address why these conventional methods may be inappropriate for monitoring of HA patients receiving emicizumab; and suggest alternative methods applicable to monitoring HA treatment in an evolving treatment landscape.

PMID:
31203578
DOI:
10.1055/s-0039-1692427

Conflict of interest statement

J.M. has received honoraria from Bayer, Novo Nordisk, Roche, and Siemens Healthcare Diagnostics for participating in advisory boards and speaker bureaus. I.P. has received honoraria or grants from LFB, Novo Nordisk, Roche, Shire, and Sobi for participating in advisory boards, speaker bureaus, and/or research. B.P. reports no conflicts of interest. B.B. is an employee of Roche and has stock ownership in Roche. J.O. has received honoraria from Bayer, Biogen, Biotest, Chugai, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and Sobi for participating in advisory boards and speaker bureaus; he has received research funding from Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, and Shire. M.S. has received grants from Shire and Pfizer, and personal fees from Roche, Sobi, LFB, Bayer, Shire, Pfizer, Uniqure, Novo Nordisk, and CSL Behring. B.B. reports personal fees from Roche Pharma AG, nonfinancial support from Gardiner-Caldwell Communications, during the conduct of the study. J.M. reports personal fees from Roche, outside the submitted work. J.O. reports grants and personal fees from Bayer, grants and personal fees from Biotest, personal fees from Chugai, grants and personal fees from CSL Behring, personal fees from Grifols, grants and personal fees from NovoNordisk, grants and personal fees from Octapharma, personal fees from Pfizer, personal fees from Roche, personal fees from SOBI, grants and personal fees from Shire, outside the submitted work. Personal fees were received for travel support, participation in Advisory Boards and participating in symposia as chair or speaker. Dr. M.S. reports nonfinancial support from Gardiner-Caldwell Communications, during the conduct of the study; grants from Shire, Pfizer, personal fees from Roche, Sobi, LFB, Bayer, Shire, Pfizer, Uniqure, Novo Nordisk, CSL Behring, outside the submitted work. I.P. reports personal fees from Sobi, LFB, Roche, Shire, grants from Novo Nordisk, outside the submitted work.

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