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Case Report
The Use of Rituximab with Immune Tolerance Induction Therapy for Hemophilia A with Inhibitors
Clin Pediatr Hematol Oncol 2015;22:67-71.
Published online April 30, 2015
© 2015 Korean Society of Pediatric Hematology-Oncology and Korean Society for Pediatric Neuro-Oncology

Chae Young Kim, M.D., Keum Nho Lee, M.D. and Young Shil Park, M.D., Ph.D.

Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul, Korea
Correspondence to: Young Shil Park
Department of Pediatrics, Kyung Hee
University Hospital at Gangdong, 892,
Dongnam-ro, Gangdong-gu, Seoul
134-727, Korea
Tel: +82-2-440-6133
Fax: +82-2-440-7175
Received March 5, 2015; Revised April 15, 2015; Accepted April 20, 2015.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Inhibitor development is one of the major adverse events associated with increased morbidity and mortality in patients with congenital hemophilia. Recent treatment for them is immune tolerance induction (ITI), which involves the administration of high doses of factor concentrates over a prolonged period, sometimes combined with immunosuppressive agents. We report a case of inhibitor elimination with Rituximab, and high-dose factor VIII concentrates in a 5-year-old boy with hemophilia A. The patient improved clinically, with fewer bleeding episodes. However, he continued to have low immunoglobulin levels, which led to recurrent infections. After an infusion of intravenous immunoglobulin, inhibitor titers increased rapidly and his ITI was deemed a failure. In conclusion, even though it failed in the present study, Rituximab may be an alternative adjuvant therapy to eliminate the inhibitor in patients with hemophilia. The appropriate schedule and long-term side effects need further investigation.
Keywords: Hemophilia, Inhibitor, Immune tolerance induction, Rituximab
  1. Brackmann HH, Oldenburg J, Schwaab R. Immune tolerance for the treatment of factor VIII inhibitors-twenty years' 'bonn protocol'. Vox Sang 1996;70:30-5.
    Pubmed CrossRef
  2. Nilsson IM, Berntorp E, Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII. N Engl J Med 1988;318:947-50.
    Pubmed CrossRef
  3. Pool JG, Gershgold EJ, Pappenhagen AR. High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate. Nature 1964;203:312.
    Pubmed CrossRef
  4. Mathias M, Khair K, Hann I, Liesner R. Rituximab in the treat-ment of alloimmune factor VIII and IX antibodies in two children with severe haemophilia. Br J Haematol 2004;125:366-8.
    Pubmed CrossRef
  5. Aleem A, Saidu A, Abdulkarim H, et al. Rituximab as a single agent in the management of adult patients with haemophilia A and inhibitors: marked reduction in inhibitor level and clinical improvement in bleeding but failure to eradicate the inhibitor. Haemophilia 2009;15:210-6.
    Pubmed CrossRef
  6. Dunkley S, Kershaw G, Young G, et al. Rituximab treatment of mild haemophilia A with inhibitors: a proposed treatment protocol. Haemophilia 2006;12:663-7.
    Pubmed CrossRef
  7. Moschovi M, Aronis S, Trimis G, Platokouki H, Salavoura K, Tzortzatou-Stathopoulou F. Rituximab in the treatment of high responding inhibitors in severe hemophilia A. Haemophilia 2006;12:95-9.
    Pubmed CrossRef
  8. Franchini M, Mengoli C, Lippi G, et al. Immune tolerance with rituximab in congenital haemophilia with inhibitors: a systematic literature review based on individual patients' analysis. Haemophilia 2008;14:903-12.
    Pubmed CrossRef
  9. Ryu JE, Park YS, Yoo KY, et al. Immune tolerance induction in patients with severe hemophilia A with inhibitors in Korea. The 64th Autumn Meeting of the Korean Pediatric Society 2014;abst 011.
  10. Gopal AK, Press OW. Clinical applications of anti-CD20 antibodies. J Lab Clin Med 1999;134:445-50.
  11. Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001;98:952-7.
    Pubmed CrossRef
  12. Quartier P, Brethon B, Philippet P, Landman-Parker J, Le Deist F, Fischer A. Treatment of childhood autoimmune haemolytic anaemia with rituximab. Lancet 2001;358:1511-3.
  13. Carcao M, St Louis J, Poon MC, et al. Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience. Haemophilia 2006;12:7-18.
    Pubmed CrossRef
  14. Collins PW, Mathias M, Hanley J, et al. Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort. J Thromb Haemost 2009;7:787-94.
    Pubmed CrossRef
  15. Noh HJ, Gong BH, Kim YS, Jung YH, Woo IS, Han CW. A case of prolonged hypogammaglobulinemia after rituximabcontaining chemotherapy in a patient with lymphoma. Korean J Med 2014;87:357-62.
  16. Walewski J, Kraszewska E, Mioduszewska O, et al. Rituximab (Mabthera, Rituxan) in patients with recurrent indolent lymphoma:evaluation of safety and efficacy in a multicenter study. Med Oncol 2001;18:141-8.

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  • Korea Hemophilia Foundation