Skip to main content
SpringerLink
Log in
Book cover

Congenital Bleeding Disorders pp 139–160Cite as

Hemophilia B

  • Chapter
  • First Online:

Abstract

Hemophilia B or Christmas disease is an X-linked recessive bleeding disorder with a prevalence of ~1 in 30,000 males worldwide that is clearly less common than hemophilia A. Patients with hemophilia B suffer from recurrent joint bleeds, ecchymosis, epistaxis, and post-dental extraction bleeding. Nevertheless women who are carriers of this abnormality are asymptomatic. Timely diagnosis of disorder is made based on family history, clinical manifestations, and appropriate laboratory studies. Replacement therapies with intravenous injection of plasma-derived factor IX (FIX) and recombinant FIX (rFIX) are current therapeutic choices that have significantly improved life expectancy and quality of life in these patients; but inhibitor formation occurring in ~1% of patients remains as a challenge of replacement therapy that can cause infused FIX concentrate to be less efficient. Gene therapy is the only definitive curative option, but some time will pass before it becomes available as a routine treatment choice.

This is a preview of subscription content, 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   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

References

  1. Horava SD, Peppas NA. Recent advances in hemophilia B therapy. Drug Deliv Transl Res. 2017;7:359–71.

    Article  CAS  PubMed  Google Scholar 

  2. DeLoughery TG. Basics of coagulation. In: Hemostasis and thrombosis. Cham: Springer; 2015. p. 1–7.

    Google Scholar 

  3. Wang Q-Y, et al. A genetic analysis of 23 Chinese patients with hemophilia B. Sci Rep. 2016;6:25024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Eby CS. Bleeding and vitamin K deficiency. In: Management of bleeding patients. Cham: Springer; 2016. p. 145–50.

    Chapter  Google Scholar 

  5. Dorgalaleh A, Dadashizadeh G, Bamedi T. Hemophilia in Iran. Hematology. 2016;21(5):300–10.

    Article  CAS  PubMed  Google Scholar 

  6. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 2012;379(9824):1447–56.

    Article  PubMed  Google Scholar 

  7. Yoshitake S, et al. Complete nucleotide sequences of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985;24(14):3736–50.

    Article  CAS  PubMed  Google Scholar 

  8. Lee C, Berntorp E, Hoots K. Textbook of hemophilia. Chichester, West Sussex, UK. Hoboken, NJ: Wiley-Blackwell; 2010.

    Book  Google Scholar 

  9. Schmidt AE, Bajaj SP. Structure–function relationships in factor IX and factor IXa. Trends Cardiovasc Med. 2003;13(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  10. Rallapalli P, et al. An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B. J Thromb Haemost. 2013;11(7):1329–40.

    Article  CAS  PubMed  Google Scholar 

  11. Ngo JCK, et al. Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure. 2008;16(4):597–606.

    Article  CAS  PubMed  Google Scholar 

  12. Autin L, et al. Molecular models of the procoagulant factor VIIIa–factor IXa complex. J Thromb Haemost. 2005;3(9):2044–56.

    Article  CAS  PubMed  Google Scholar 

  13. Li T, et al. The CDC Hemophilia B mutation project mutation list: a new online resource. Mol Genet Genomic Med. 2013;1(4):238–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li T, et al. Mutation analysis of a cohort of US patients with hemophilia B. Am J Hematol. 2014;89(4):375–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mannucci P, Franchini M. Is haemophilia B less severe than haemophilia A? Haemophilia. 2013;19(4):499–502.

    Article  CAS  PubMed  Google Scholar 

  16. Jedidi I, et al. Acquired haemophilia B: a case report and literature review. Ann Biol Clin. 2011;69:685–8.

    Google Scholar 

  17. Franchini M, Mannucci PM. Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice. Br J Clin Pharmacol. 2011;72(4):553–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Crossley M, et al. Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter. Science. 1992;257(5068):377–9.

    Article  CAS  PubMed  Google Scholar 

  19. DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol. 2007;138(3):305–15.

    Article  CAS  PubMed  Google Scholar 

  20. Ulrich S, et al. Congenital hypersensitivity to vitamin K antagonists due to FIX propeptide mutation at locus-10: a (not so) rare cause of bleeding under oral anticoagulant therapy in Switzerland. Swiss Med Wkly. 2008;138(7–8):100–7.

    PubMed  CAS  Google Scholar 

  21. Chu K, et al. A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. J Clin Investig. 1996;98(7):1619.

    Article  CAS  PubMed  Google Scholar 

  22. Oldenburg J, et al. Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy. Br J Haematol. 1997;98(1):240–4.

    Article  CAS  PubMed  Google Scholar 

  23. Surin V, et al. Mutational analysis of hemophilia B in Russia: molecular-genetic study. Russ J Genet. 2016;52(4):409–15.

    Article  CAS  Google Scholar 

  24. Kitchen S, McCraw A, Echenagucia M. Diagnosis of hemophilia and other bleeding disorders. A laboratory manual. Montreal: World Federation of Hemophilia; 2000.

    Google Scholar 

  25. Kihlberg K, et al. Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B. Haemophilia. 2017;23(4):620–7.

    Article  CAS  PubMed  Google Scholar 

  26. Kitchen S, Signer-Romero K, Key N. Current laboratory practices in the diagnosis and management of haemophilia: a global assessment. Haemophilia. 2015;21(4):550–7.

    Article  CAS  PubMed  Google Scholar 

  27. Sellner LN, Taylor GR. MLPA and MAPH: new techniques for detection of gene deletions. Hum Mutat. 2004;23(5):413–9.

    Article  CAS  PubMed  Google Scholar 

  28. KWON MJ, et al. Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B. Haemophilia. 2008;14(5):1069–75.

    Article  CAS  PubMed  Google Scholar 

  29. Bolton-Maggs PH, Pasi KJ. Haemophilias a and b. Lancet. 2003;361(9371):1801–9.

    Article  CAS  PubMed  Google Scholar 

  30. Franchini M, et al. Treatment of hemophilia B: focus on recombinant factor IX. Biol Targets Ther. 2013;7:33.

    Article  CAS  Google Scholar 

  31. Elm T, Oestergaard H, Tranholm M. Dose response and prolonged effect of 40K PEG-FIX on bleeding in hemophilia B mice. J Thromb Haemost. 2009;7:134.

    Google Scholar 

  32. Carcao M, et al. Insight into health-related quality of life of young children with haemophilia B treated with long-acting nonacog beta pegol recombinant factor IX. Haemophilia. 2017;23(3):e222–4.

    Article  CAS  PubMed  Google Scholar 

  33. Metzner HJ, et al. Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Thromb Haemost. 2009;102(4):634–44.

    PubMed  CAS  Google Scholar 

  34. Brown DL. Congenital bleeding disorders. Curr Probl Pediatr Adolesc Health Care. 2005;35(2):38–62.

    Article  PubMed  Google Scholar 

  35. Nummi V, Jouppila A, Lassila R. Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with thrombin generation assay and factor IX activity. Int J Lab Hematol. 2017;39:359–68.

    Article  CAS  PubMed  Google Scholar 

  36. Dolan G, et al. Haemophilia B: Where are we now and what does the future hold? Blood Rev. 2017;32:52–60.

    Article  CAS  PubMed  Google Scholar 

  37. Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol. 2004;127(4):379–91.

    Article  CAS  Google Scholar 

  38. White G, et al. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 2001;85(3):560.

    Article  CAS  PubMed  Google Scholar 

  39. Nathwani AC, et al. Adenovirus-associated virus vector–mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nienhuis AW, Nathwani AC, Davidoff AM. Gene therapy for hemophilia. Mol Ther. 2017;25:1163–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Nathwani AC, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;2014(371):1994–2004.

    Article  CAS  Google Scholar 

  42. Park C-Y, et al. Genome-editing technologies for gene correction of hemophilia. Hum Genet. 2016;135(9):977–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kay MA, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet. 2000;24(3):257.

    Article  CAS  PubMed  Google Scholar 

  44. Herzog RW, et al. Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat Med. 1999;5(1):56.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We appreciate Professor Edward Tuddenham for his valuable comments that significantly improved the quality of this chapter.

Author information

Authors and Affiliations

  1. Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

    Hoda Motlagh & Akbar Dorgalaleh

  2. Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany

    Behnaz Pezeshkpoor

Authors
  1. Hoda Motlagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Behnaz Pezeshkpoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akbar Dorgalaleh
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Iran University of Medical Sciences, Departement of Hematology and Blood TransfusionSchool of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

    Akbar Dorgalaleh

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Motlagh, H., Pezeshkpoor, B., Dorgalaleh, A. (2018). Hemophilia B. In: Dorgalaleh, A. (eds) Congenital Bleeding Disorders . Springer, Cham. https://doi.org/10.1007/978-3-319-76723-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-76723-9_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-76722-2

  • Online ISBN: 978-3-319-76723-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation