Experience of Immune Tolerance Induction Therapy for Hemophilia A Patients with Inhibitors from a Single Center in India

Abstract

The availability of clotting factor concentrates of both factor VIII and factor IX have improved hemophilia treatment to a great extent. Many more improvements like physiotherapy, and comprehensive care are needed to give better care. One important complication that occurs, but is often set aside is the development of inhibitors. When an inhibitor develops in a patient of severe hemophilia then the care becomes more difficult and expensive. Eradication of the inhibitor is possible by Immune tolerance induction (ITI), this paper explains some important essential factors and practical issues during my experience with ITI.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Wight J, Paisley S (2003) The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia 9:418–443

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Witmer C, Young G (2013) Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol 4(1):59–72

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Pinto P, Shelar T, Nawadkar V, Mirgal D, Mukaddam A, Nair P et al (2014) The Epidemiology of FVIII Inhibitors in Indian Haemophilia A Patients. Indian J Hematol blood Transfus 30(4):356–363

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Kar A, Phadnis S, Dharmarajan S, Nakade J (2014) Epidemiology & social costs of haemophilia in India. Indian J Med Res 140:19–31

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Ghosh K, Ghosh K (2016) Management of Haemophilia in developing countries: challenges and options. Indian J Hematol Blood Transfus 32(3):347–355

    PubMed  Article  Google Scholar 

  6. 6.

    Saxena K (2013) Barriers and perceived limitations to early treatment of hemophilia. J Blood Med 4:49–56

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Colowick AB, Bohn RL, Avorn J, Ewenstein BM (2000) Immune tolerance induction in hemophilia patients with inhibitors: costly can be cheaper. Blood 96(5):1698–1702

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Rocha P, Carvalho M, Lopes M, Araújo F (2015) Costs and utilization of treatment in patients with hemophilia. BMC Health Serv Res 15:484. https://doi.org/10.1186/s12913-015-1134-3

    PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Elisa Mancuso M, Cannavo A (2015) Immune tolerance induction in hemophilia. Clin Investig 5:321–335

    Article  Google Scholar 

  10. 10.

    Valentino LA, Kempton CL, Kruse-Jarres R, Mathew P, Meeks SL, Reiss UM (2015) US Guidelines for immune tolerance induction in patients with haemophilia A and inhibitors. Haemophilia 21:559–567

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Miller CH (2018) Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review. Haemophilia 24(2):186–197

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Adcock DM, Favaloro EJ (2015) Pearls and pitfalls in factor inhibitor assays. Int Jnl Lab Hem 37(1):52–60

    Article  Google Scholar 

  13. 13.

    Kempton CL, Meeks SL (2014) Toward optimal therapy for inhibitors in hemophilia. Hematol Am Soc Hematol Educ Program 2014:364–371

    Article  Google Scholar 

  14. 14.

    Valentino LA, Allen G, Gill JC, Hurlet A, Konkle BA, Leissinger CA et al (2013) Case studies in the management of refractory bleeding in patients with haemophilia A and inhibitors. Haemophilia 19(3):e151–e166

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G et al (2017) Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med 377(9):809–818

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Sherman A, Biswas M, Herzog RW (2017) Innovative approaches for immune tolerance to factor VIII in the treatment of Hemophilia A. Front Immunol 8:1604. https://doi.org/10.3389/fimmu.2017.01604

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Mauz-Korholz C, Korholz D, Gobel U (1997) Rapid elimination of a high-titered F VIII inhibitor by high dose recombinant F VIII combined with high dose immunoglobulin infusion. Thromb Haemost 78:959

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Mauser-Bunschoten EP, Karel Nieuwenhuis H, Roosendaal G, Marijke van den Berg G (1995) Low-dose immune tolerance induction in Hemophilia A patients with inhibitors. Blood 86(3):983–988

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Kavakli UK, Baytan B, Kazanci E, Sayli TY, Oren H, Celkan T, Gurse T (2008) Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors. Haemophilia 14:315–322

    PubMed  Article  Google Scholar 

  20. 20.

    Berntorp E, Astermark J, Carlborg E (2000) Immune tolerance induction and the treatment of hemophilia. Malmö protocol update. Haematologica 85(10):48–50

    CAS  PubMed  Google Scholar 

  21. 21.

    Hay CRM, DiMichele DM (2012) The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood 119(6):1335–1344

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Malec LM, Journeycake J, Ragni MV (2016) Extended half-life factor VIII for immune tolerance induction in haemophilia. Haemophilia 22(6):e552–e554

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Brackmann H-H, White GC 2nd, Berntorp E, Andersen T, Escuriola-Ettingshausen C (2018) Immune tolerance induction: what have we learned over time? Haemophilia 24(3):3–14

    PubMed  Article  Google Scholar 

  24. 24.

    Escuriola Ettingshausen C, Kreuz W (2013) The immune tolerance induction (ITI) dose debate: does the International ITI study provide a clearer picture? Haemophilia 19(1):12–17

    PubMed  Article  Google Scholar 

  25. 25.

    Minno GD (2014) Predictors of ITI success according to evidence from literature data. Haemophilia 20(6):27–43

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Jimenez-Yuste V, Oldenburg J, Rangarajan S, Peiro-Jordan R, Santagostino E (2016) Long-term outcome of haemophilia A patients after successful immune tolerance induction therapy using a single plasma-derived FVIII/VWF product: the long-term ITI study. Haemophilia 22(6):859–865

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Barnes C, Brown SA, Curtin J, Dunkley S (2014) When is enough… enough? Developing consensus of definition of failure of immune tolerance induction in patients with haemophilia and inhibitors. Haemophilia 20:e275–e279

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Tulika Seth.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Seth, T. Experience of Immune Tolerance Induction Therapy for Hemophilia A Patients with Inhibitors from a Single Center in India. Indian J Hematol Blood Transfus 36, 458–463 (2020). https://doi.org/10.1007/s12288-019-01218-2

Download citation

Keywords

  • Eradication of inhibitors
  • Inherited hemophilia