A special thanks to Dr. Cristina Tarango, director of the Hemophilia Treatment Center at Cincinnati Children’s and Lisa Littner, Project Manager at Cincinnati Children’s who helped me research and write this post.
…and it’s called Hemlibra (Emicizumab)
Why this med is important and why kids are on it?
Emicizumab (Hemlibra) was approved in 2018 for routine bleeding prophylaxis in hemophilia A with or without inhibitors. Emicizumab is not a factor concentrate like we use to treat kids with acute bleeds. It is a humanized, monoclonal bispecific antibody that binds activated factor IX and factor X. By simultaneously binding enzyme and substrate, emicizumab mimics one of the functions of FVIII. Emicizumab, though, does not fully normalize hemostasis. Rather, it can change the bleeding phenotype from severe hemophilia to mild hemophilia – thus potentially reducing the risk of complications. An increasing number of children and adolescents with hemophilia A are on Hemlibra, and therefor the purpose of this post is to educate and raise awareness. It is therefore no hyperbole to say that Emicizumab has been a life-changing therapy for individuals with hemophilia A who have factor VIII inhibitors (alloantibodies against factor VIII). Emicizumab allows these individuals to have good bleed control, improvement in their joint health and their quality of life.
However, FVIII and the bispecific antibody are fundamentally different proteins and subject to different modes of regulation.
How to know if a patient is on it?
Patients on emicizumab will have it listed on their medication list. Patients/caregivers should also be able to tell you if they are on emicizumab (Hemlibra).
How is it different than factor concentrate?
Emicizumab cannot be used to treat an acute bleeding episode like factor can. Emciziumab, unlike factor, does not normalize hemostasis. This means that when someone on emizumab gets injured or has bleeding, they still need to receive factor concentrate.
Emicizumab requires 4 weekly loading doses to get to steady state.
The concomitant use of FEIBA in individuals with hemophilia A and inhibitors on emiziumab can cause thrombosis or thrombotic microangiopathy. This is a black box warning. Fortuntately, recombinant activated factor VIIa (NovoSeven) can be still used in individuals on emicizumab if they have bleeding episodes.
Despite these cautions, emicizumab has several advantages over factor concentrate prophylaxis. Emiciziumab is given subcutaneously rather than intravenously, and it has a much longer half-life. Individuals on emicizumab can be dosed once a week, every 2 weeks or every 4 weeks. That has decreased the burden of treatment for many individuals with severe hemophilia A (factor VIII levels <1%) or those with moderate hemophilia A (factor VIII levels 1-5%) with a severe bleeding phenotype.
How are the labs we (might) need to obtain different?
It is important to know that emicizumab interfers with common coagulation testing. Emicizumab affects the aPTT by shortening it, even though circulating factor VIII levels are very low. Because most standard factor activity assays for factor VIII are aPTT-based, factor VIII levels on emicizumab are inaccurately elevated (as are factor IX, XI, XII levels). These effects on coagulation testing can be seen up to 6 months after a dose of emicizumab. Many ED providers may get a factor VIII level to decide if a patient needs factor treatment if a patient is already on “prophylaxis.” Life-threatening bleeding due to unreliable standard coagulation tests in the setting of emicizumab is classified as an important potential risk of taking this medication. And finally…
Any individual with hemophilia who either comes in with bleeding or a significant injury should receive factor concentrate, regardless of what drug they use for prophylaxis. Factor first!
For more information on global efforts to care for patients with hemophilia and the recent World Hemophilia Day check out the World Hemophilia Day – WFH – World Federation of Hemophilia
References
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Jiménez-Yuste V, Peyvandi F, Klamroth R, Castaman G, Shanmukhaiah C, Rangarajan S, García Chavez J, Martinez R, Kenet G, Alzahrani H, Robson S, Schmitt C, Kiialainen A, Meier O, Ozelo M. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022 Nov 14;6(8):e12837. doi: 10.1002/rth2.12837. PMID: 36397934; PMCID: PMC9663319.
Mahlangu J, Iorio A, Kenet G. Emicizumab state-of-the-art update. Haemophilia. 2022 May;28 Suppl 4(Suppl 4):103-110. doi: 10.1111/hae.14524. PMID: 35521723; PMCID: PMC9321850.
Hassan E, Jonathan L, Jayashree M. Real-world experience on the tolerability and safety of emicizumab prophylaxis in paediatric patients with severe haemophilia A with and without FVIII inhibitors. Haemophilia. 2021 Nov;27(6):e698-e703. doi: 10.1111/hae.14432. Epub 2021 Oct 10. PMID: 34628693.
Nardi MA. Hemophilia A: Emicizumab monitoring and impact on coagulation testing. Adv Clin Chem. 2023;113:273-315. doi: 10.1016/bs.acc.2022.12.001. Epub 2023 Jan 16. PMID: 36858648.
