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

  • Tulika SethEmail author
Review Article


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.


Eradication of inhibitors Inherited hemophilia 



  1. 1.
    Wight J, Paisley S (2003) The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia 9:418–443CrossRefGoogle Scholar
  2. 2.
    Witmer C, Young G (2013) Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol 4(1):59–72CrossRefGoogle 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):356–363CrossRefGoogle Scholar
  4. 4.
    Kar A, Phadnis S, Dharmarajan S, Nakade J (2014) Epidemiology & social costs of haemophilia in India. Indian J Med Res 140:19–31PubMedPubMedCentralGoogle Scholar
  5. 5.
    Ghosh K, Ghosh K (2016) Management of Haemophilia in developing countries: challenges and options. Indian J Hematol Blood Transfus 32(3):347–355CrossRefGoogle Scholar
  6. 6.
    Saxena K (2013) Barriers and perceived limitations to early treatment of hemophilia. J Blood Med 4:49–56CrossRefGoogle 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):1698–1702CrossRefGoogle 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. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Elisa Mancuso M, Cannavo A (2015) Immune tolerance induction in hemophilia. Clin Investig 5:321–335CrossRefGoogle 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 21:559–567CrossRefGoogle Scholar
  11. 11.
    Miller CH (2018) Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review. Haemophilia 24(2):186–197CrossRefGoogle Scholar
  12. 12.
    Adcock DM, Favaloro EJ (2015) Pearls and pitfalls in factor inhibitor assays. Int Jnl Lab Hem 37(1):52–60CrossRefGoogle Scholar
  13. 13.
    Kempton CL, Meeks SL (2014) Toward optimal therapy for inhibitors in hemophilia. Hematol Am Soc Hematol Educ Program 2014:364–371CrossRefGoogle 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–e166CrossRefGoogle 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):809–818CrossRefGoogle 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. CrossRefPubMedPubMedCentralGoogle 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 78:959CrossRefGoogle 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):983–988CrossRefGoogle 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 14:315–322CrossRefGoogle Scholar
  20. 20.
    Berntorp E, Astermark J, Carlborg E (2000) Immune tolerance induction and the treatment of hemophilia. Malmö protocol update. Haematologica 85(10):48–50PubMedGoogle Scholar
  21. 21.
    Hay CRM, DiMichele DM (2012) The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood 119(6):1335–1344CrossRefGoogle 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–e554CrossRefGoogle 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):3–14CrossRefGoogle 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):12–17CrossRefGoogle Scholar
  25. 25.
    Minno GD (2014) Predictors of ITI success according to evidence from literature data. Haemophilia 20(6):27–43CrossRefGoogle 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):859–865CrossRefGoogle 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–e279CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  1. 1.Room 5017, Teaching BlockAIIMSAnsari Nagar, New DelhiIndia

Personalised recommendations