open access

Vol 10, No 1 (2017)
Review paper
Published online: 2017-04-04
Get Citation

Management of children with haemophilia complicated by inhibitor

Paweł Łaguna, Anna Klukowska
Journal of Transfusion Medicine 2017;10(1):12-18.

open access

Vol 10, No 1 (2017)
REVIEWS
Published online: 2017-04-04

Abstract

The occurrence of factor VIII or factor IX inhibitor following treatment of haemophilia A or B patients with factor VIII or IX concentrates is a serious complication of the disease. In the presence of these inhibitors the replacement treatment is ineffective. Therefore the immediate goal in the management of haemophilia complicated by the inhibitor is to arrest bleeding while the ultimate aim is to eliminate the inhibitor permanently. We present the management of children with haemophilia complicated by inhibitor.

Abstract

The occurrence of factor VIII or factor IX inhibitor following treatment of haemophilia A or B patients with factor VIII or IX concentrates is a serious complication of the disease. In the presence of these inhibitors the replacement treatment is ineffective. Therefore the immediate goal in the management of haemophilia complicated by the inhibitor is to arrest bleeding while the ultimate aim is to eliminate the inhibitor permanently. We present the management of children with haemophilia complicated by inhibitor.

Get Citation

Keywords

haemophilia; inhibitor; immune tolerance induction (ITI); children

About this article
Title

Management of children with haemophilia complicated by inhibitor

Journal

Journal of Transfusion Medicine

Issue

Vol 10, No 1 (2017)

Article type

Review paper

Pages

12-18

Published online

2017-04-04

Bibliographic record

Journal of Transfusion Medicine 2017;10(1):12-18.

Keywords

haemophilia
inhibitor
immune tolerance induction (ITI)
children

Authors

Paweł Łaguna
Anna Klukowska

References (43)
  1. Valentino LA, Pipe SW, Tarantino MD, et al. Healthcare resource utilization among haemophilia A patients in the United States. Haemophilia. 2012; 18(3): 332–338.
  2. Ananyeva NM, Lacroix-Desmazes S, Hauser CAE, et al. Inhibitors in hemophilia A: mechanisms of inhibition, management and perspectives. Blood Coagul Fibrinolysis. 2004; 15(2): 109–124.
  3. Ehrenforth S, Kreuz W, Scharrer I, et al. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet. 1992; 339(8793): 594–598.
  4. Carcao M, Re W, Ewenstein B. The role of previously untreated patient studies in understanding the development of FVIII inhibitors. Haemophilia. 2016; 22(1): 22–31.
  5. Gouw SC, van der Bom JG, Ljung R, et al. PedNet and RODIN Study Group. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013; 368(3): 231–239.
  6. Iorio A, Halimeh S, Holzhauer S, et al. Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review. J Thromb Haemost. 2010; 8(6): 1256–1265.
  7. Franchini M, Coppola A, Rocino A, et al. ; Italian Association of Hemophilia Centers (AICE) Working Group. Systematic review of the role of FVIII concentrates in inhibitor development in previously untreated patients with severe hemophilia a: a 2013 update. Semin Thromb Hemost. 2013; 39(7): 752–766.
  8. Peyvandi F, Mannucci PM, Garagiola I, et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016; 374(21): 2054–2064.
  9. Windyga J, Chojnowski K, Klukowska A, et al. Zasady postępowania w hemofilii A i B powikłanej inhibitorem. Acta Haematol. , 2008; 39. ; 3: 565–578.
  10. Negrier C, Dargaud Y, Bordet JC. Basic aspects of bypassing agents. Haemophilia. 2006; 12 Suppl 6: 48–52; discussion 52.
  11. Ragni M.V., Dimchele M., Hay C.M et al.: Thrombin generation and bleeding in haemophilia inhibitor patents during immune tolerance induction. Haemophilia 2016:22,240-247.
  12. Teitel J, Berntorp E, Dolan G, et al. A consensus statement on clinical trials of bypassing agent prophylaxis in inhibitor patients. Haemophilia. 2011; 17(3): 516–521.
  13. Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood. 2007; 109(2): 546–551.
  14. Schneiderman J, Nugent DJ. G. Young. Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe haemophilia and inhibitors 2004,10. ; 4: 347–351.
  15. Schneiderman J, Rubin E, Nugent DJ, et al. Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience. Haemophilia. 2007; 13(3): 244–248.
  16. Rocino A, Papa ML, Salerno E, et al. 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.
  17. Brackmann HH. Induced immunotolerance in factor VIII inhibitor patients. Prog Clin Biol Res. 1984; 150: 181–195.
  18. Mariani G, Kroner B. International immune tolerance registry, 1997 update. Vox Sang. 1999; 77 Suppl 1: 25–27.
  19. Lenk H. ITT Study Group. The German Registry of immune tolerance treatment in hemophilia--1999 update. Haematologica. 2000; 85(10 Suppl): 45–47.
  20. Damiano ML, Hutter JJ. Immune tolerance for haemophilia patients with inhibitors: analysis of the western United States experience. The Tri-Regional Nursing Group. Haemophilia. 2000; 6(5): 526–532.
  21. Astermark J, Morado M, Rocino A, et al. EHTSB. Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors. Haemophilia. 2006; 12(4): 363–371.
  22. IITI. International, Randomized, Controlled Trial of Immune-tolerance Induction. Available at: http://www.itistudy.com
  23. Dolgin E. Immunology: Oral solutions. Nature. 2014; 515(7528): S166–S167.
  24. Markusic DM, Hoffman BE, Perrin GQ, et al. Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies. EMBO Mol Med. 2013; 5(11): 1698–1709.
  25. Escuriola-Ettingshausen C, et al. Martinez Saguer I. Funk M.B. : Long-term prophylaxiswith FEIBA® in patients with high-responding inhibitors. J Thromb Haemost. 2003; 1(Suppl): P1628.
  26. Ewing N.: Anamnestic responses in hemophilia patients with inhibitors un continuous prophylaxis with factor eight inhibitor bypassing activity, vapor heated (FEIBA VH). J. Thromb. Haemost., 2005; 3(Suppl.1): P2036.
  27. Kreuz W., Escuriola-Ettingshausen C., Martinez I. et al.: Efficacy and safety of factor VIII inhibitor bypass activity (Feiba)for long-term prophylaxis in patients with high-responding inhibitors. Blood, 2000; 96: 1140.
  28. Lambert T., Fressinaud E., Goudemand J. et al.: Can long-term prophylaxis with APCC improve the bleeding rate and quality of life of frequently bleeding haemophiliacs with inhibitor? Haemophilia, 2006; 12(Suppl. 2): 14 PO 399.
  29. Saxena K, et al. Hawk S. Stevens B. : Long-term clinical experience with FEIBA VH in hemophilia patients with inhibitors. J Thromb Haemost. 2005; 3(Suppl.1): P0838.
  30. Siegmund B, Richter H, Pollmann H. Prophylactic treatment with FEIBA of a haemophilia A patient with inhibitor: what are the costs, what are the benefits? Haemophilia. 2005; 11(6): 638–641.
  31. VALENTINO LA. FEIBA prophylaxis for patients with haemophilia and inhibitors. Haemophilia. 2006; 12(s5): 26–31.
  32. Dimichele D, Négrier C. A retrospective postlicensure survey of FEIBA efficacy and safety. Haemophilia. 2006; 12(4): 352–362.
  33. Lindley CM, Sawyer WT, Macik BG, et al. Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. Clin Pharmacol Ther. 1994; 55(6): 638–648.
  34. Villar A, Aronis S, Morfini M, et al. Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven) in children vs. adults with haemophilia A. Haemophilia. 2004; 10(4): 352–359.
  35. Klukowska A, Łaguna P, Obitko-Płudowska A, et al. Zastosowanie aktywowanego rekombinowanego czynnika VII (rFVIIa) w leczeniu dzieci chorych na hemofilię A z wysokim mianem inhibitora. Acta Haematol Pol. 1998; 29: 401–6.
  36. Konkle B.A., Ebbesen L.S., Friedrich U. et al.: Secondary prophylactic treatment with rFVIIa in patients with haemophilia A or B and inhibitors with high requirements for on-demand treatment: analysis of primary endpoint and safety. Vancouver, Canada: Poster presented at: XXVII International Congress of the World Federation of Hemophilia; 21–5 May 2006.
  37. Saxon BR, Shanks D, Jory CB, et al. Effective prophylaxis with daily recombinant factor VIIa (rFVIIa-Novoseven) in a child with high titre inhibitors and a target joint. Thromb Haemost. 2001; 86(4): 1126–1127.
  38. Young G, McDaniel M, Nugent DJ. Prophylactic recombinant factor VIIa in haemophilia patients with inhibitors. Haemophilia. 2005; 11(3): 203–207.
  39. Fox RA, Neufeld EJ, Bennett CM. Rituximab for adolescents with haemophilia and high titre inhibitors. Haemophilia. 2006; 12(3): 218–222.
  40. Warrier I, Baird-Cox K, Lusher JM. Use of central venous catheters in children with haemophilia: one haemophilia treatment centre experience. Haemophilia. 1997; 3(3): 194–198.
  41. Klukowska A., Łaguna P , Rawicz M. Zasady postępowania w zakładaniu cewników centralnych u chorych na wrodzone osoczowe skazy krwotoczne- doświadczenia własne Medycyna wieku Rozwojowego 2008,XII,4 II 1126-1129
  42. W. Kreuz, C. Escuriola Ettingshausen, V. Vdovin, N. Zozulya, First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/ von Willebrand factor concentrate in an observational immune tolerance induction study, Haemophilia. 2016; 22: 87–95.
  43. Evans M, Cottrell D, Shiach C. Emotional and behavioural problems and family functioning in children with haemophilia: a cross-sectional survey. Haemophilia. 2000; 6(6): 682–687.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Journal of Transfusion Medicine dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest Via Medica sp. z o.o. sp. komandytowa, ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl