Yonsei Med J.  2013 Jan;54(1):71-80. 10.3349/ymj.2013.54.1.71.

Prevalence, Incidence, and Factor Concentrate Usage Trends of Hemophiliacs in Taiwan

• Tu TC
• Liou WS
• Chou TY
• Lin TK
• Lee CF
• Chen JD
• Cham TM
• Chung MI

• KMID: 1776920
• DOI: http://doi.org/10.3349/ymj.2013.54.1.71

Abstract

PURPOSE
Hemophilia A and B (HA, HB) are the most common X-linked inherited bleeding disorders. The introduction of factor concentrates has allowed for control of the lifelong chronic disease. However, no studies have been published regarding the epidemiology of hemophilia in Taiwan. Our aim was to determine the prevalence, incidence, and mortality rate, as well as trends in the use of factor concentrates, in individuals with hemophilia in Taiwan.
MATERIALS AND METHODS
A retrospective study was conducted using the National Health Insurance Research Database between 1997 and 2007.
RESULTS
We identified 988 males with hemophilia (HA : HB ratio=5.4 : 1). The mean prevalence per 100000 males was 6.7+/-0.1 for HA and 1.2+/-0.1 for HB. The estimated mean annual incidence per live male birth was 1 in 10752 for HA and 1 in 47619 for HB. Standardized mortality ratios for males with hemophilia (all severities) or severe hemophilia were 1.3- and 2.1-fold higher than that of the general male population, respectively. Mean factor VIII (FVIII) and factor IX (FIX) usage was 1.5003+/-0.4029 and 0.3126+/-0.0904 international units (IUs) per capita, respectively. Mean FVIII and FIX usage per patient with hemophilia (all severities) or severe hemophilia was 44027+/-11532 and 72341+/-17298, respectively, and 49407+/-13015 and 74369+/-18411 IUs per person with HA or HB, respectively.
CONCLUSION
Our data revealed epidemiologic and factor concentrate usage trends in males with hemophilia in Taiwan, highlighting a need for improvements in the mandatory National Health Insurance registry. A better-designed, patient-centered registry system would enable more detailed patient information collection and analysis, improving subsequent care.

Keyword

Hemophilia; prevalence; incidence; factor VIII; factor IX; Taiwan

MeSH Terms

Adolescent
Adult
Aged
Child
Child, Preschool
Databases, Factual
Factor IX/therapeutic use
Factor VIII/therapeutic use
Hemophilia A/*drug therapy/*epidemiology/ethnology
Hemophilia B/*drug therapy/*epidemiology/ethnology
Humans
Incidence
Infant
Male
Middle Aged
Prevalence
Registries
Retrospective Studies
Taiwan/epidemiology
Young Adult
Factor IX
Factor VIII

Figure

• 

  Fig. 1 Flow chart for inclusion.

• 

  Fig. 2 Mean incidence (per 100000 male livebirths per year) with 5 years interval during the 1978-2007 period. HA, hemophilia A; HB, hemophilia B.

• 

  Fig. 3 Flow chart for inclusion of factor usage data.

• 

  Fig. 4 Age-distribution prevalence (per 100000 males) on December 31, 2007. HA, hemophilia A; HB, hemophilia B.

Reference

1. Fischer K, Van Den Berg M. Prophylaxis for severe haemophilia: clinical and economical issues. Haemophilia. 2003. 9:376–381.

2. Mannucci PM, Tuddenham EG. The hemophilias--from royal genes to gene therapy. N Engl J Med. 2001. 344:1773–1779.

3. Darby SC, Kan SW, Spooner RJ, Giangrande PL, Hill FG, Hay CR, et al. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood. 2007. 110:815–825.

4. Franchini M, Tagliaferri A, Mannucci PM. The management of hemophilia in elderly patients. Clin Interv Aging. 2007. 2:361–368.

5. Plug I, Van Der Bom JG, Peters M, Mauser-Bunschoten EP, De Goede-Bolder A, Heijnen L, et al. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost. 2006. 4:510–516.

6. Street A, Hill K, Sussex B, Warner M, Scully MF. Haemophilia and ageing. Haemophilia. 2006. 12:Suppl 3. 8–12.

7. Plug I, Peters M, Mauser-Bunschoten EP, de Goede-Bolder A, Heijnen L, Smit C, et al. Social participation of patients with hemophilia in the Netherlands. Blood. 2008. 111:1811–1815.

8. Guidelines for the management of hemophilia. 2005. accessed on 2012 Aug 8. Available at: http://wfh.org/2/docs/Publications/Diagnosis_and_Treatment/Guidelines_Mng_Hemophilia.pdf.

9. Cherishing health insurance for a healthy Taiwan 2006. accessed on 2012 Aug 8. Available at: http://www.nhi.gov.tw/Resource/webdata/Attach_13792_2_cherishing.pdf.

10. National Health Insurance in Taiwan 2011 Annual Report. accessed on 2012 Aug 8. Available at: http://www.nhi.gov.tw/Resource/webdata/13767_1_NHI%20IN%20TAIWAN%202011%20ANNUAL%20REPORT.pdf.

11. Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJ, Lozano R, Inoue M. Age Standardization of rates: a new WHO standard. 2001. accessed on 2010 Aug 8. Available at: http://www.who.int/healthinfo/paper31.pdf.

12. Population by age. accessed on 2010 Aug 8. Available at: http://sowf.moi.gov.tw/stat/year/y02-01.xls.

13. Causes of death statistics. accessed on 2010 Aug 8. Available at: http://www.doh.gov.tw/CHT2006/DisplayStatisticFile.aspx?d=73104&s=1.

14. Stonebraker JS, Brooker M, Amand RE, Farrugia A, Srivastava A. A study of reported factor VIII use around the world. Haemophilia. 2010. 16:33–46.

15. StataCorp LP, 4905 Lakeway Drive College Station, Texas 77845-4512, USA.

16. Stonebraker JS, Bolton-Maggs PH, Soucie JM, Walker I, Brooker M. A study of variations in the reported haemophilia A prevalence around the world. Haemophilia. 2010. 16:20–32.

17. Ling SC, Chan GCF, Shing MMK, Yuen HL, Lee ACW, Chan CW, et al. Children and Adolescents with Haemophilia in Hong Kong: an Epidemiological and Clinical Review. HK J Paediatr. 2006. 11:13–19.

18. Plug I, van der, Peters M, Mauser-Bunschoten EP, de Goede-Bolder A, Heijnen L, et al. Thirty years of hemophilia treatment in the Netherlands, 1972-2001. Blood. 2004. 104:3494–3500.

19. Iorio A, Oliovecchio E, Morfini M, Mannucci PM. Association of Italian Hemophilia Centres Directors. Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis. Haemophilia. 2008. 14:444–453.

20. Annual Report 2009. United Kingdom Haemophilia Centre Doctors' Organisation 2009. accessed on 2010 Aug 8. Available at: http://www.ukhcdo.org/docs/AnnualReports/2009/Annual%20Report%202009%20slides.pdf.

21. Canadian Hemophilia registry-Factor VIII. Hemophilia A 2009. accessed on 2010 Aug 8. Available at: http://fhs.mcmaster.ca/chr/pdf/09/CHRVIII090413.pdf.

22. Soucie JM, Evatt B, Jackson D. Occurrence of hemophilia in the United States. The Hemophilia Surveillance System Project Investigators. Am J Hematol. 1998. 59:288–294.

23. Stonebraker JS, Bolton-Maggs PHB, Soucie JM, Walker I, Brokker M. A study of variations in the reported hemophilia B prevalence around the world. accessed on 2011 Dec 10. Available at: http://www1.wfh.org/2/docs/Publications/Statistics/FF-10_Prevalence_HemophiliaB.pdf.

24. Canadian Hemophilia registry-Factor IX. Hemophilia B 2009. accessed on 8 Aug 2010. Available at: http://fhs.mcmaster.ca/chr/pdf/09/CHRIX090413.pdf.

25. Chan V, Chan TK, Liu VW, Wong AC. Restriction fragment length polymorphisms associated with factor VIII: C gene in Chinese. Hum Genet. 1988. 79:128–131.

26. Chen YC, Hu SH, Cheng SN, Chao TY. Genetic analysis of haemophilia A in Taiwan. Haemophilia. 2010. 16:538–544.

27. Tagliaferri A, Rivolta GF, Iorio A, Oliovecchio E, Mancuso ME, Morfini M, et al. Mortality and causes of death in Italian persons with haemophilia, 1990-2007. Haemophilia. 2010. 16:437–446.

28. Mejia-Carvajal C, Czapek EE, Valentino LA. Life expectancy in hemophilia outcome. J Thromb Haemost. 2006. 4:507–509.

29. Cases of HIV/AIDS by exposure category. accessed on 2012 Aug 8. Available at: http://www.cdc.gov.tw/downloadfile.aspx?fid=BFFEE6AB018CFAF8.

30. Statistics of HIV/AIDS 1984-2003/1/31. accessed on 2010 Aug 8. Available at: http://www2.cdc.gov.tw/public/Data/8121710212971.pdf.

31. Statistics of HIV/AIDS 1984-2007/12/31. accessed on 2010 Aug 8. Available at: http://www.cdc.gov.tw/english/info.aspx?treeid=00ed75d6c887bb27&nowtreeid=1d256e6c8b243c1d&tid=1E0691878D687950.

32. Berntorp E, Boulyjenkov V, Brettler D, Chandy M, Jones P, Lee C, et al. Modern treatment of haemophilia. Bull World Health Organ. 1995. 73:691–701.

33. Ono O, Suzuki Y, Yosikawa K, Wada I, Doi Y, Takano M, et al. Assessment of haemophilia treatment practice pattern in Japan. Haemophilia. 2009. 15:1032–1038.

34. Carcao MD, Aledort LM. Round Table Group. Prophylaxis in the haemophilia population-optimizing therapy. Haemophilia. 2007. 13:227–232.

35. Smith PS, Teutsch SM, Shaffer PA, Rolka H, Evatt B. Episodic versus prophylactic infusions for hemophilia A: a cost-effectiveness analysis. J Pediatr. 1996. 129:424–431.

36. Carlsson KS, Höjgård S, Lindgren A, Lethagen S, Schulman S, Glomstein A, et al. Costs of on-demand and prophylactic treatment for severe haemophilia in Norway and Sweden. Haemophilia. 2004. 10:515–526.

37. Heemstra HE, Zwaan T, Hemels M, Feldman BM, Blanchette V, Kern M, et al. Cost of severe haemophilia in Toronto. Haemophilia. 2005. 11:254–260.

38. Liou WS, Tu TC, Cheng SN, Chou TY, Lee CF, Lin TK, et al. Secondary prophylaxis treatment versus on-demand treatment for patients with severe haemophilia A: comparisons of cost and outcomes in Taiwan. Haemophilia. 2011. 17:45–54.

39. Coppola A, Franchini M, Tagliaferri A. Prophylaxis in people with haemophilia. Thromb Haemost. 2009. 101:674–681.

40. Ettingshausen CE, Kreuz W. Recombinant vs. plasma-derived products, especially those with intact VWF, regarding inhibitor development. Haemophilia. 2006. 12:Suppl 6. 102–106.

41. Wight J, Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia. 2003. 9:418–435.

42. Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H, et al. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006. 107:46–51.

43. Gouw SC, van der Bom JG, Auerswald G, Ettinghausen CE, Tedgård U, van den Berg HM. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood. 2007. 109:4693–4697.

44. Chalmers EA, Brown SA, Keeling D, Liesner R, Richards M, Stirling D, et al. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia. 2007. 13:149–155.

45. Coppola A, Santoro C, Tagliaferri A, Franchini M, DI Minno G. Understanding inhibitor development in haemophilia A: towards clinical prediction and prevention strategies. Haemophilia. 2010. 16:Suppl 1. 13–19.

46. Geraghty S, Dunkley T, Harrington C, Lindvall K, Maahs J, Sek J. Practice patterns in haemophilia A therapy -- global progress towards optimal care. Haemophilia. 2006. 12:75–81.