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hemophilia B; factor IX deficiency ; Christmas disease

Epidemiology: - occurs in men - less common than hemophilia A (0.1) Genetics: 1) X-linked recessive 2) transmitted from unaffected mother to male offspring Clinical manifestations: 1) history of spontaneous bleeding since childhood 2) excessive bleeding following surgery & dental procedures 3) recurrent hemarthrosis leading to contractures & crippling degenerative joint disease 4) hemorrhages into muscle 5) excessive bleeding from minor trauma 6) easy bruising 7) no excessive bleeding after minor cuts 8) clinically indistinguishable from hemophilia A, 9) female carriers are asymptomatic. Laboratory: 1) complete blood count (CBC) - evaluate anemia 2) prothrombin time (PT) is normal 3) prolonged partial thromboplastin time (PTT) 4) mixing studies: - correction of PTT with normal serum or factor IX 5) factor IX plasma activity: < 1% of normal (severe) [2] 6) PCR/southern blot 7) see ARUP consult [3] Complications: - factor 9 inhibitors (up to 3-5%) Management: 1) fresh frozen plasma 2) cryoprecipitate 3) factor 9 concentrate 5) recombinant factor IXa (Benefix) 6) recombinant factor IX Fc fusion protein (Aprolix) - longer 1/2 life than Benefix, weekly or longer 7) gene therapy [5] - intravenous infusion of a single dose of a factor IX transgene delivered with an adenovirus vector - 4 of 7 patients able to discontinue Benefix vs Aprolix - beneficial effects in all 7 patients up to 3 years 8) exercise reasonable for children with hemophilia [4] Notes: - in 1952, one of the early researchers of the disease, Dr. R.G. Macfarlane used the patient's surname, Christmas, to refer to the disease & also to refer to the clotting factor which he called the 'christmas factor' - at the time. Stephen Christmas was a 5-year-old boy - he died in 1993 at the age of 46 from AIDS contracted through treatment with blood products

Related

coagulation factor IX; Christmas factor; plasma thromboplastin component; PTC; contains: coagulation factor IXa light chain; coagulation factor IXa heavy chain (F9) factor IX gene mutation hemophilia A; factor VIII deficiency

General

hemophilia X-linked disease

Database Correlations

OMIM 306900

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 885
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2022
  3. ARUP Consult: Hemophilia - Factor VIII or IX Deficiency The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hemophilia
  4. Broderick CR et al Association Between Physical Activity and Risk of Bleeding in Children With Hemophilia JAMA. 2012;308(14):1452-1459 PMID: 23047359 http://jama.jamanetwork.com/article.aspx?articleid=1377921 - Manco-Johnson MJ Collision Sports and Risk of Bleeding in Children With Hemophilia JAMA. 2012;308(14):1480-1481 PMID: 23047364 http://jama.jamanetwork.com/article.aspx?articleid=1377908
  5. Nathwani AC et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014 Nov 20; 371:1999 PMID: 25409372 http://www.nejm.org/doi/full/10.1056/NEJMoa1407309
  6. Anello J, Feinberg B, Heinegg J et al Hemophilia Guidelines on management of acute joint bleeds and chronic synovitis in hemophilia by the United Kingdom Haemophilia Centre Doctors' Organisation. Medscape: New Guidelines and Recommendations, August 2017. http://reference.medscape.com/viewarticle/884517