Volume 1 (2013): Issue 1

Successful immune tolerance in two children with severe haemophilia A

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Bert Leenders

Abstract

Abstract

Haemophilia A is an X-linked congenital bleeding disorder resulting from a deficiency of factor VIII (FVIII). Therapy to prevent or treat bleeding is by replacement of the missing FVIII. However, as a consequence of treatment, patients with HA may develop inhibitory IgG antibodies to FVIII, termed “inhibitors”. When this occurs, treatment becomes more complex and costly and morbidity increases. Inhibitor formation, occurring in up to 36% of patients with severe HA, is currently one of the most significant complications affecting patients with HA [1,2]. In these two case studies, the management of bleeds in patients with inhibitors, and the long-term inhibitor eradication will be discussed.

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References

  • 1. Darby SC, Keeling DM, Spooner RJ, et al. The incidence of factor VIII and factor IX inhibitors in the haemophilia population of the UK and their effect on subsequent mortality, 1977-99. J Thromb Haemost 2004; 2:1047-1054.
  • 2. Ehrenforth S, Kreuz W, Scharrer I, et al. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet 1992; 339: 594-598.
  • 3. Roberts HR, Monroe DM, White GC. The use of recombinate factor VIIa in the treatment of bleeding disorders. Blood 2004; 104: 3858-3864.
  • 4. Lindley CM, Sawyer WT, Macik BG, et al. Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. Clin Pharmacol Ther 1997; 55: 638-648.
  • 5. Yatuv R, Dayan I, Carmel-Goren L, et al. Enhancement of factor VIIa haemostatic efficacy by formulation with PEGylated liposomes. Haemophilia 2008; 14: 476-483
  • 6. Weimer T, Wormsbächer W, Kronthaler U, et al. Prolonged in-vivo half life of factor VIIa by fusion to albumin. Thromb Haemost 2008; 99: 659-667
  • 7. Leissinger C, Gringeri A, Antmen B, et al. Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors. N Engl J Med 2011; 365: 1684-92.
  • 8. Manco-Johnson MJ, Abshire TC, Schapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe haemophilia. N Engl J Med 2007; 357: 535-544.
  • 9. Konkle BA, Ebbesen LS, Erhardtsen E, et al. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in haemophilia patients with inhibitors. J Thromb Haemost 2007; 5: 1904-1913.
  • 10. Hay CR, DiMichele DM. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood 2012; 119: 1335-1344
  • 11. DiMichele DM, Kroner BL. The North American Immune Tolerance Registry: practices, outcomes, outcome predictors. Thromb Haemost 2002; 87: 52-57.
  • 12. Mariani G, Kroner B. Immune Tolerance in haemophilia with factor VIII inhibitors: predictors of success. Haematologica 2001; 86: 1186-1193.
  • 13. Kruez W, Ettingshausen CE, Zyschka A, et al. Inhibitor development in previously untreated patients with haemophilia A: a prospective long-term follow-up comparing plasma-derived and recombinant products. Semin Thromb Hemost 2002; 28: 285-290.
  • 14. Kruez W. Immune tolerance and choice of concentrates. In: Lee C, ed. Inhibitors in patients with haemophilia. Oxford: Blackwell Science Ltd. 2002; 55-56.
  • 15. Berntorp E. Importance of rapid bleeding control in haemophilia complicated by inhibitors. Haemophilia 2001; 17: 1116.

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