Articles, Issue 1/2025

Laboratory Мonitoring of Patients with haemophilia A Undergoing Routine Prophylaxis with Emicizumab

Posted on by admin

A. Banchev1,2, A. Bedran3

1 Expert Center for Hemophilia, Thalassemia and Other Rare Benign Hematological Diseases, Clinic of Pediatric Clinical Hematology and Oncology, Tsaritsa Ioanna University Hospital – ISUL, Sofia, Bulgaria, Department of Pediatrics, MU – Sofia 2 National Haematology Hospital – Sofia, Bulgaria 3 Clinical Laboratory, University Hospital “Tsaritsa

Abstract

Haemophilia A (HA) is an X-linked inherited bleeding disorder caused by a deficiency in the activity of coagulation factor (F) VIII. One of the major complications of HA treatment is the development of neutralizing alloantibodies known as FVIII inhibitors. Emicizumab is a humanized monoclonal antibody modified immunoglobulin G4 (IgG4) with a bispecific antibody structure. Emicizumab binds activated factor IX and factor X, thereby restoring the function of missing FVIIIa, which is required for effective hemostasis. Fundamental structural and functional differences between emicizumab and FVIII affect the results of some standard laboratory assays when conducted in the presence of emicizumab. This paper discusses current methods for laboratory monitoring of patients with HA, including activated partial thromboplastin time, a one-step FVIII activity assay, a chromogenic FVIII activity assay, and a Bethesda assay based on the one-step FVIII activity assay; explain why these conventional methods may be inappropriate for monitoring patients with HA receiving emicizumab and suggest alternative methods applicable to monitoring HA treatment in patients undergoing prophylactic therapy with emicizumab.

Key words: haemophilia A, laboratory monitoring,  micizumab,  coagulation

To access this content, you must purchase Годишен абонамент.

Bibliography

  1. Банчев А, Стоянова Т, Бедран А, Стоянова Д, Константинов Д. Коагулационни тестове в светлината на новостите в хемофилната грижа – стара песен на нов глас. Хематология. 2020; (1-2):32-37. ISSN 2367-7864.
  2. Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev 2013; 27(04):179–184;
  3. Hemlibra КХП
  4. Adamkewicz JI, Chen DC, Paz-Priel I. Thromb Haemost 2019; 119(07):1084–1093.
  5. Müller J, et al. Thromb Haemost 2019;119:1384–1393.
  6. WFH Guidelines for the Management of Hemophilia, 3rd edition. Doi: https://doi.org/10.1111/hae.14046
  7. Van Dijk K, van der BomJG, Lenting PJ, et al. Haematologica 2005; 90(04):494–498.
  8. Pipe S, ShimaM, Lehle M, et al. Lancet Haematol 2019. Doi: https://doi.org/10.1016/S2352-3026(19)30054-7
  9. Mahlangu J, Oldenburg J, Paz-Priel I, et al. N Engl J Med 2018; 379(09):811–822.
  10. Oldenburg J, Mahlangu JN, Kim B, et al. N Engl J Med 2017;377(09):809–818.
  11. Young G, Sidonio RF, Liesner R, et al. Emicizumab prophylaxis provides flexible and effective bleed control in children with hemophilia A with inhibitors: results from the HAVEN 2 Study. ASH December 1–4, 2018; San Diego, CA.
  12. Lenting PJ, Denis CV, Christophe OD. Blood 2017; 130(23):2463–2468.

Address for correspondence: 

Clinic of Pediatric Clinical Hematology and

Oncology, University Hospital “Tsarina Ioanna – ISUL”

8, “Byalo more”, Str. 

1527, Sofia, Bulgaria 

e-mail: bantschev@isul.eu