Laboratory Monitoring in Patients Receiving Emicizumab

Jens Müller; Martin Büchsel; Olga Oleshko; Behnaz Pezeshkpoor; Ulrich Sachs; Ute Scholz; Andreas Tiede

doi:10.1055/a-2687-0107

Hämostaseologie, Table of Contents

Hamostaseologie
DOI: 10.1055/a-2687-0107

Original Article

Laboratory Monitoring in Patients Receiving Emicizumab

Authors

Jens Müller

¹Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
Martin Büchsel

²Institute for Clinical Chemistry and Laboratory Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Olga Oleshko

³Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
Behnaz Pezeshkpoor

¹Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
Ulrich Sachs

⁴Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
Ute Scholz

⁵Center of Coagulation Disorders, Leipzig, Germany
Andreas Tiede

³Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

Abstract

Emicizumab is a bispecific monoclonal antibody that mimics the cofactor function of activated factor VIII (FVIIIa). It is approved for routine prophylaxis in patients with severe or moderate congenital hemophilia A (HA), both with and without FVIII inhibitors, and is increasingly used as a first-line treatment in acquired HA (AHA). Owing to its predictable pharmacokinetic profile, emicizumab monitoring is generally limited to cases with suspected reduced efficacy, such as due to poor adherence or the development of anti-drug antibodies (ADAs). However, emicizumab interferes with standard clotting assays, particularly by shortening activated partial thromboplastin times (APTT). To address this, modified FVIII one-stage clotting assays (mOSA), which use higher sample pre-dilution and emicizumab-specific calibration, are commonly employed to estimate plasma levels, although other assay formats like emicizumab-calibrated chromogenic substrate assays based on human factors or liquid chromatography tandem mass spectrometry are also available. Additionally, global assays such as in vitro thrombin generation testing are being explored to better reflect clinical hemostatic efficacy. This review summarizes current knowledge on assay interferences caused by emicizumab, challenges in functional measurement of plasma levels, and strategies to ensure reliable laboratory assessment. We also discuss the relevance and methods for ADA detection and provide an overview of current and emerging strategies for thrombin generation measurement as a global indicator of treatment effectiveness.

Keywords

hemophilia A - blood coagulation tests - emicizumab - factor VIII - drug monitoring

Full Text

References

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