Skip to main content
SpringerLink
Log in

The Incidence of Inhibitors in Hemophilia A and the Induction of Immune Tolerance

  • Chapter
Hemophilia Care in the New Millennium

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 489))

Abstract

The risk of inhibitor development is highly variable and depends on a number of factors: the definition of risk, the assay method and the threshold level, the persistence of the inhibitor, the frequency of measurements, and also on specific patient factors and treatment factors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Verbruggen B, Novakova I, Wessels H, Boezeman J, van dB, Mauser-Bunschoten E. The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. Thromb Haemost 1995; 73: 247–251.

    PubMed  CAS  Google Scholar 

  2. Giles AR, Verbruggen B, Rivard GE, Teitel J, Walker I. A detailed comparison of the performance of the standard versus the Nijmegen modification of the Bethesda assay in detecting factor VIII:C inhibitors in the haemophilia A population of Canada. Association of Hemophilia Centre Directors of Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee of International Society on Thrombosis and Haemostasis. Thromb Haemost 1998; 79: 872–875.

    PubMed  CAS  Google Scholar 

  3. Kasper CK, Aledort LM, Counts RB. A more uniformed measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869–782.

    Google Scholar 

  4. Hofmann SL. Southwestern Internal Medicine Conference: Shiga-like toxins in hemolyticuremic syndrome and thrombotic thrombocytopenic purpura Am J Med Sci 1993; 306: 398–406.

    Article  PubMed  CAS  Google Scholar 

  5. Hay CR, Ludlam CA, Colvin BT, et al. Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation. Thromb Haemost 1998; 79: 762–766.

    PubMed  CAS  Google Scholar 

  6. Schwaab R, Brackmann HH, Meyer C, et al. Haemophilia A: mutation type determines risk of inhibitor formation. Thromb Haemost 1995; 74: 1402–1406.

    PubMed  CAS  Google Scholar 

  7. Muller HP, van Tilburg NH, Bertina RM, Veltkamp D. Heterogeneity of haemophilia A: a study with three different antisera. Br J Haematol 1982; 52: 485–494.

    Article  PubMed  CAS  Google Scholar 

  8. Hay CR, Oilier W, Pepper L, et al. HLA class II profile: a weak determinant of factor VIII inhibitor development in severe haemophilia A. UKHCDO Inhibitor Working Party. Thromb Haemost 1997;77: 234–237.

    Google Scholar 

  9. Oldenburg J, Picard JK, Schwaab R, Brackmann HH, Tuddenham EG, Simpson E. HLA genotype of patients with severe haemophilia A due to intron 22 inversion with and without inhibitors of factor VIII. Thromb Haemost 1997; 77: 238–242.

    PubMed  CAS  Google Scholar 

  10. Peerlinck K, Amout J, Gilles JG, Saint-Remy JM, Vermylen J. A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate [see comments]. Thromb Haemost 1993; 69: 115–118.

    PubMed  CAS  Google Scholar 

  11. Rosendaal FR, Nieuwenhuis HK, Van den Berg HM, et al. A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Blood 1993; 81: 2180–2186.

    PubMed  CAS  Google Scholar 

  12. McMillan CW, Shapiro SS, Whitehurst D, et al. The natural history of factor VIII:C inhibitors in patients with hemophilia A: A national comparative study. II. Observations on the initial development of factor VIII:C inhibitors. Blood 1988; 71: 344–348.

    PubMed  CAS  Google Scholar 

  13. Peerlinck K, Amout J, Di GM, et al. Factor VIII inhibitors in previously treated haemophilia A patients with a double virus-inactivated plasma derived factor VIII concentrate. Thromb Haemost 1997; 77: 80–86.

    PubMed  CAS  Google Scholar 

  14. Mauser-Bunschoten EP, Rosendaal FR, Nieuwenhuis HK, Roosendaal G, Briët E, Van den Berg HM. Clinical course of factor VIII inhibitors developed after exposure to a pasteurised Dutch concentrate compared to classic inhibitors in hemophilia A. Thromb Haemost 1994; 71: 703–706.

    Google Scholar 

  15. Guerois C, Laurian Y, Rothschild C, et al. Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. Thromb Haemost 1995; 73: 215–218.

    PubMed  CAS  Google Scholar 

  16. Yee TT, Williams MD, Hill FG, Lee CA, Pasi KJ. Absence of inhibitors in previously untreated patients with severe haemophilia A after exposure to a single intermediate purity factor VIII product. Thromb Haemost 1997; 78: 1027–1029.

    PubMed  CAS  Google Scholar 

  17. Vermylen J. How do some haemophiliacs develop inhibitors?. [Review] [29 refs]. Haemophilia 1998; 4: 538–542.

    Article  PubMed  CAS  Google Scholar 

  18. Lusher JM, Arkin S, Abildgaard CF, Schwartz RS, and the Kogenate Previously Untreated Patient Group. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A--Safety, efficacy, and development of inhibitors. N Engl J Med 1993; 328: 453–459.

    Article  PubMed  CAS  Google Scholar 

  19. Bray GL, Gomperts ED, Courter S, et al. A multicenter study of recombinant factor VIII (Recombinate): Safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. Blood 1994; 83: 2428–2435.

    PubMed  CAS  Google Scholar 

  20. Briet E, Rosendaal FR, Kreuz W, et al. High titer inhibitors in severe haemophilia A. A meta-analysis based on eight long-term follow-up studies concerning inhibitors associated with crude or intermediate purity factor VIII products (letter to the editor). Thromb Haemost 1994; 72: 162–164.

    PubMed  CAS  Google Scholar 

  21. Brackmann HH, Oldenburg J, Schwaab R. Immune tolerance for the treatment of factor VIII inhibitors--twenty years“bonn protocol’. Vox Sang 1996; 70 Suppl 1: 30–35.

    Article  PubMed  Google Scholar 

  22. 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: 947–950.

    Article  PubMed  CAS  Google Scholar 

  23. Smith MP, Spence KJ, Waters EL, et al. Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution. Thromb Haemost 1999; 81: 35–38.

    PubMed  CAS  Google Scholar 

  24. Ewing NP, Sanders NL, Dietrich SL, Kasper CK. Induction of immune tolerance to factor VIII in hemophiliacs with inhibitors. JAMA 1988; 259: 65–85.

    Article  PubMed  CAS  Google Scholar 

  25. Gruppo RA. Immune tolerance induction with once weekly factor VIII infusions in patients with hemophilia A and inhibitors (abstract). Thromb Haemost 1991; 65 (Suppl): 1168–1168.

    Google Scholar 

  26. Mauser-Bunschoten EP, Nieuwenhuis HK, Roosendaal G, van den Berg HM. Low-dose immune tolerance induction in hemophilia A patients with inhibitors. Blood 1995; 86: 983–988.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of internal medicine and pediatrics, Academic medical center, Amsterdam, The Netherlands

    Ernest Briët & Marjolein Peters

Authors
  1. Ernest Briët
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marjolein Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Dougald M. Monroe

  2. Novo Nordisk A/S, Målov, Denmark

    Ulla Hedner

  3. University of Lund, Lund, Sweden

    Ulla Hedner

  4. Duke University and Durham VA Medical Centers, Durham, North Carolina, USA

    Maureane R. Hoffman

  5. Hôpital Edouard Herriot, Lyon, France

    Claude Negrier

  6. Guys’ and St. Thomas’s Trust, London, UK

    Geoffrey F. Savidge

  7. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Gilbert C. White II

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Briët, E., Peters, M. (2001). The Incidence of Inhibitors in Hemophilia A and the Induction of Immune Tolerance. In: Monroe, D.M., Hedner, U., Hoffman, M.R., Negrier, C., Savidge, G.F., White, G.C. (eds) Hemophilia Care in the New Millennium. Advances in Experimental Medicine and Biology, vol 489. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1277-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1277-6_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5474-1

  • Online ISBN: 978-1-4615-1277-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation