Routine measurements of factor VIII activity and inhibitor titer in the presence of emicizumab utilizing anti‐idiotype monoclonal antibodies

Nogami, Keiji; Soeda, Tetsuhiro; Matsumoto, Tomoko; Kawabe, Yojiro; Kitazawa, Takio; Shima, Midori

doi:10.1111/jth.14135

Cited by 70 publications

(70 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Emicizumab does not require activation by thrombin and its effect on the aPTT is more pronounced than that of factor FVIII . aPTT‐based FVIII activity and FVIII inhibitor titre measurements are influenced by the presence of emicizumab.…”

Section: Changes In Haemostasis Tests In Patients Receiving Emicizumabmentioning

confidence: 99%

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra^®): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP)

et al. 2019

View full text Add to dashboard Cite

Introduction: Emicizumab (Hemlibra ® ) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A patients with inhibitor. This implicates a multidisciplinary approach and redaction of recommendations for care that must be regularly adapted to the available data. Aim:The following text aims to provide a guide for the management of people with haemophilia A with inhibitor treated with emicizumab in case of bleeding or invasives procedures.

show abstract

Section: Changes In Haemostasis Tests In Patients Receiving Emicizumabmentioning

confidence: 99%

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra^®): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP)

et al. 2019

View full text Add to dashboard Cite

show abstract

“…58 Including recombinant anti-idiotype anti-emicizumab monoclonal antibodies in one-stage assays has been shown to prevent interference by emicizumab, resulting in accurate measurements of both FVIII activity and inhibitor titers. 59 One study did demonstrate a relationship between one-stage FVIII and emicizumab levels; however, this required method modification which may not be readily implemented in laboratories and this relationship requires further verification. 60 Current guidance states that the level of emicizumab must be measured with a chromogenic two-stage assay using human components as emicizumab does not recognise non-human FIXa or FX.…”

Section: Effect Of a Fviii-mimicking Humanised Antibody Product On mentioning

confidence: 99%

Clinical utility and impact of the use of the chromogenic vs one‐stage factor activity assays in haemophilia A and B

Marlar

Strandberg

Shima

et al. 2019

European J of Haematology

View full text Add to dashboard Cite

Treatment of haemophilia A/B patients comprises factor VIII (FVIII) or factor IX (FIX) concentrate replacement therapy, respectively. FVIII and FIX activity levels can be measured in clinical laboratories using one‐stage activated partial thromboplastin time (aPTT)‐based clotting or two‐stage chromogenic factor activity assays. We discuss strengths and limitations of these assays, providing examples of clinical scenarios to highlight some of the challenges associated with their current use for diagnostic and monitoring purposes. Substantial inter‐laboratory variability has been reported for one‐stage assays when measuring the activity of factor replacement products due to the wide range of currently available aPTT reagents, calibration standards, factor‐deficient plasmas, assay conditions and instruments. Chromogenic activity assays may avoid some limitations associated with one‐stage assays, but their regulatory status, perceived higher cost, and lack of laboratory expertise may influence their use. Haemophilia management guidelines recommend the differential application of one or both assays for initial diagnosis and disease severity characterisation, post‐infusion monitoring and replacement factor potency labelling. Efficient communication between clinical and laboratory staff is crucial to ensure application of the most appropriate assay to each clinical situation, correct interpretation of assay results and, ultimately, accurate diagnosis and optimal and safe treatment of haemophilia A or B patients.

show abstract

“…As mentioned above, emicizumab interacts only with human and primate FIXa/FX, and therefore chromogenic assays using bovine reagents could be helpful in these circumstances. Another option could be the use of anti‐idiotype monoclonal antibodies against emicizumab 34 . Emicizumab activity is completely neutralized by anti‐FIX(a) and FX(a) Fab antibodies.…”

Section: Questions For the Wider Use Of Emicizumab In The Postmarketimentioning

confidence: 99%

Bispecific Antibodies and Advances in Non–Gene Therapy Options in Hemophilia

Shima

2020

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Regular prophylaxis has markedly improved the treatment for patients with hemophilia A, especially after the introduction of highly purified factor VIII (FVIII) concentrates. However, frequent intravenous infusions and the development of FVIII inhibitors remain as unsolved difficulties. To overcome these unmet needs, a bispecific antibody mimicking activated FVIII has been developed in Japan. This bispecific antibody, emicizumab, recognizes activated factor IX (FIXa) and activated factor X (FXa), and promotes FIXa‐catalyzed activation of FX in the absence of FVIII. Emicizumab initially reacts with FIXa generated by the action of factor VIIa/tissue factor complexes. Subsequently, thrombin generation is enhanced in the presence of higher amounts of FIXa derived from FXIa‐dependent mechanisms. Hence, emicizumab‐driven FXa and thrombin generation is maintained by a FXI activation loop in the intrinsic coagulation pathway. Reactions downstream of emicizumab are regulated by natural anticoagulants including activated protein C, antithrombin, and tissue factor pathway inhibitor. Phase 3 studies (HAVEN 1‐4 and HOHOEMI studies) demonstrated a remarkable reduction in bleeding rates together with a high percentage of patients with zero treated bleeds irrespective of the presence of inhibitors. In general, emicizumab proved to be well tolerated, although isolated thromboembolic and thrombotic microangiopathic complications were observed in the HAVEN 1 studies, and 3 out of a total of 400 patients developed neutralizing antidrug antibodies. In addition, several questions remain to be discussed with respect to open‐use clinical practice, including when to start treatment, how to monitor therapy, and optimum dosage for surgical procedures and immune tolerance induction.

show abstract

Routine measurements of factor VIII activity and inhibitor titer in the presence of emicizumab utilizing anti‐idiotype monoclonal antibodies

Cited by 70 publications

References 14 publications

Clinical utility and impact of the use of the chromogenic vs one‐stage factor activity assays in haemophilia A and B

Bispecific Antibodies and Advances in Non–Gene Therapy Options in Hemophilia

Contact Info

Product

Resources

About