Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep;25(5):789-796.
doi: 10.1111/hae.13819. Epub 2019 Aug 2.

Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving emicizumab prophylaxis

Glaivy Batsuli  1 , Karen L Zimowski  1 , Kelly Tickle  2 , Shannon L Meeks  1 , Robert F Sidonio Jr  1
Affiliations

Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving emicizumab prophylaxis

Glaivy Batsuli et al. Haemophilia. 2019 Sep.

Abstract

Introduction: The formation of neutralizing antifactor VIII (fVIII) antibodies, called inhibitors, is the most common complication in modern haemophilia A care. Novel non-factor replacement therapies, such as emicizumab, have sought to address the limitations of bypassing agents for bleeding management in patients with inhibitors. However, immune tolerance induction (ITI) remains the primary method for eradicating inhibitors and restoring the hemostatic response to fVIII.

Aim: The aim of this study was to review a case series of paediatric patients with haemophilia A and inhibitors who have received ITI for inhibitor eradication concomitantly with emicizumab prophylaxis for bleeding prevention.

Methods: Single institution retrospective chart review of paediatric patients with severe haemophilia A receiving ITI and emicizumab.

Results: Seven patients were included in this cohort. Six patients used three different recombinant fVIII products at 100 IU/kg three times per week, and one patient used a plasma-derived fVIII product at an initial dose of 50 IU/kg three times per week. Three patients achieved a negative inhibitor titre <0.6 Chromogenic Bethesda Units per mL (CBU/mL), and two patients achieved a normal fVIII recovery ≥66%. There were nine bleeding events in four patients, but no thrombotic events. All patients remained on ITI and emicizumab.

Conclusion: Immune tolerance induction while on emicizumab prophylaxis is a feasible approach in paediatric haemophilia A patients with inhibitors. This is the first report of the concomitant use of ITI in patients receiving emicizumab prophylaxis described as the 'Atlanta Protocol'.

Keywords: bypassing agents; emicizumab; haemophilia A; immune tolerance; inhibitors; paediatrics.

PubMed Disclaimer

References

REFERENCES

    1. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544.
    1. Darby SC, Keeling DM, Spooner RJD, et al. The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977-99. J Thromb Haemost. 2004;2(7):1047-1054.
    1. DiMichele DM, Kroner BL. The North American immune tolerance registry: practices, outcomes, outcome predictors. Thromb Haemost. 2002;87(1):52-57.
    1. Mariani G, Ghirardini A, Bellocco R. Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee. Thromb Haemost. 1994;72(1):155-158.
    1. Rocino A, Papa ML, Salerno E, Capasso F, Miraglia E, de Biasi R. Immune tolerance induction in haemophilia A patients with high-responding inhibitors to factor VIII: experience at a single institution. Haemophilia. 2001;7(1):33-38.

LinkOut - more resources