Public health issues in the thalassemic syndromes
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Beta thalassemia occurs in the Mediterranean littoral and all over Southeast Asia (Burma, Thailand, Cambodia, Vietnam, China, Malaysia, Indonesia, and the Philippines). Alpha thalassemia is even more common, occurring with high frequency throughout all tropical and subtropical regions, including most of Southeast Asia, the Mediterranean area, the Indian subcontinent, the Middle East, and Africa [1,2].
Some variants of thalassemia (eg, hydrops fetalis with hemoglobin Bart's) are incompatible with life , while others (eg, beta thalassemia major) are associated with lifelong transfusion-dependent anemia, short stature, facial abnormalities, delayed or absent puberty, and attendant stigmas and psychosocial problems [4,5].
Of major public health importance, individuals with one of the various forms of thalassemia trait may be entirely asymptomatic, unaware of their diagnosis, and procreate with other individuals with the same trait, thereby perpetuating the disorder within these communities. (See "Clinical manifestations and diagnosis of the thalassemias".)
An interesting anecdote illustrates our changing perceptions about these disorders. Thalassemia was not diagnosed in Cyprus before 1944 . After World War II, following improvements in public health along with malarial eradication programs, it became apparent that there was a newly recognized but common hypochromic microcytic anemia in children not due to iron deficiency (ie, severe beta thalassemia) . It was quickly realized that, for example, the cost of red blood cell transfusions and chelation therapy per year for a patient with beta thalassemia major exceeded by three to four orders of magnitude the per capita funds available for health care in that country, as well as in much of the developing world.
By 1970, it was projected that, if this disease was not controlled, by the year 2000 the cost of treatment of these children would consume the entire health care budget of Cyprus and require all of the blood that the island could supply, even supposing that 40 percent of the adults would enlist as regular blood donors.
- Weatherall DJ. Thalassemia in the next millennium. Keynote address. Ann N Y Acad Sci 1998; 850:1.
- Piel FB, Weatherall DJ. The α-thalassemias. N Engl J Med 2014; 371:1908.
- Chui DH, Waye JS. Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem. Blood 1998; 91:2213.
- Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann N Y Acad Sci 1998; 850:251.
- Politis C. The psychosocial impact of chronic illness. Ann N Y Acad Sci 1998; 850:349.
- Lorey F, Cunningham G. Impact of Asian immigration on thalassemia in California. Ann N Y Acad Sci 1998; 850:442.
- Vichinsky EP. Clinical manifestations of α-thalassemia. Cold Spring Harb Perspect Med 2013; 3:a011742.
- Rees DC, Styles L, Vichinsky EP, et al. The hemoglobin E syndromes. Ann N Y Acad Sci 1998; 850:334.
- Chui DH, Cunningham MJ, Luo HY, et al. Screening and counseling for thalassemia. Blood 2006; 107:1735.
- Luo HY, Boudreaux J, Steinberg MH, Chui DH. Patients with thalassemia in the United States. Blood 2005; 105:4896.
- Vichinsky EP, MacKlin EA, Waye JS, et al. Changes in the epidemiology of thalassemia in North America: a new minority disease. Pediatrics 2005; 116:e818.
- Padilla CD, Therrell BL. Newborn screening in the Asia Pacific region. J Inherit Metab Dis 2007; 30:490.
- de Silva S, Fisher CA, Premawardhena A, et al. Thalassaemia in Sri Lanka: implications for the future health burden of Asian populations. Sri Lanka Thalassaemia Study Group. Lancet 2000; 355:786.
- Higgs DR. alpha-Thalassaemia. Baillieres Clin Haematol 1993; 6:117.
- Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and disease complications in thalassemia major. Ann N Y Acad Sci 1998; 850:227.
- Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci 1998; 850:191.
- Storb R, Yu C, Deeg HJ, et al. Current and future preparative regimens for bone marrow transplantation in thalassemia. Ann N Y Acad Sci 1998; 850:276.
- Caocci G, La Nasa G, d'Aloja E, et al. Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients. BMC Med Ethics 2011; 12:4.
- Yin A, Zhang L, Luo M, et al. Development of bead-based suspension array technology for the diagnosis of thalassemia. Am J Hematol 2014; 89:1158.
- Widayanti CG, Ediati A, Tamam M, et al. Feasibility of preconception screening for thalassaemia in Indonesia: exploring the opinion of Javanese mothers. Ethn Health 2011; 16:483.
- Flint J, Hill AV, Bowden DK, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature 1986; 321:744.
- Modiano G, Morpurgo G, Terrenato L, et al. Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population. Am J Hum Genet 1991; 48:390.
- Samavat A, Modell B. Iranian national thalassaemia screening programme. BMJ 2004; 329:1134.
- Beris P, Darbellay R, Extermann P. Prevention of beta-thalassemia major and Hb Bart's hydrops fetalis syndrome. Semin Hematol 1995; 32:244.
- Liao C, Mo QH, Li J, et al. Carrier screening for alpha- and beta-thalassemia in pregnancy: the results of an 11-year prospective program in Guangzhou Maternal and Neonatal hospital. Prenat Diagn 2005; 25:163.
- Ballantyne A, Newson A, Luna F, Ashcroft R. Prenatal diagnosis and abortion for congenital abnormalities: is it ethical to provide one without the other? Am J Bioeth 2009; 9:48.
- Yurkiewicz IR, Korf BR, Lehmann LS. Prenatal whole-genome sequencing--is the quest to know a fetus's future ethical? N Engl J Med 2014; 370:195.
- Fiorentino F, Biricik A, Karadayi H, et al. Development and clinical application of a strategy for preimplantation genetic diagnosis of single gene disorders combined with HLA matching. Mol Hum Reprod 2004; 10:445.
- Verlinsky Y, Rechitsky S, Sharapova T, et al. Preimplantation HLA testing. JAMA 2004; 291:2079.
- Choy J, Yamashita RC, Foote D, et al. Outreach strategies for Asian Pacific Island (API) communities. Ann N Y Acad Sci 1998; 850:514.
- Weissman L, Treadwell M, Foote D, et al. Approaches to working with adult thalassemia patients in pediatric settings. Ann N Y Acad Sci 1998; 850:516.
- Weatherall DJ, Clegg JB. Thalassemia--a global public health problem. Nat Med 1996; 2:847.
- Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families for genetic hemoglobin disorders in Pakistan. N Engl J Med 2002; 347:1162.
- Cao A, Galanello R. Effect of consanguinity on screening for thalassemia. N Engl J Med 2002; 347:1200.
- Di Palma A, Vullo C, Zani B, Facchini A. Psychosocial integration of adolescents and young adults with thalassemia major. Ann N Y Acad Sci 1998; 850:355.
- Bozkurt G. Results from the north cyprus thalassemia prevention program. Hemoglobin 2007; 31:257.
- Hvistendahl M. Genetic disease. China heads off deadly blood disorder. Science 2013; 340:677.
- Leung KY, Lee CP, Tang MH, et al. Cost-effectiveness of prenatal screening for thalassaemia in Hong Kong. Prenat Diagn 2004; 24:899.
- Ostrowsky JT, Lippman A, Scriver CR. Cost-benefit analysis of a thalassemia disease prevention program. Am J Public Health 1985; 75:732.
- Ahmadnezhad E, Sepehrvand N, Jahani FF, et al. Evaluation and cost analysis of national health policy of thalassaemia screening in west-azerbaijan province of iran. Int J Prev Med 2012; 3:687.
- Ginsberg G, Tulchinsky T, Filon D, et al. Cost-benefit analysis of a national thalassaemia prevention programme in Israel. J Med Screen 1998; 5:120.
- Koren A, Profeta L, Zalman L, et al. Prevention of β Thalassemia in Northern Israel - a Cost-Benefit Analysis. Mediterr J Hematol Infect Dis 2014; 6:e2014012.
- Zeuner D, Ades AE, Karnon J, et al. Antenatal and neonatal haemoglobinopathy screening in the UK: review and economic analysis. Health Technol Assess 1999; 3:i.
- Streetly A. A national screening policy for sickle cell disease and thalassaemia major for the United Kingdom. Questions are left after two evidence based reports. BMJ 2000; 320:1353.
- Heer N, Choy J, Vichinsky EP. The social impact of migration on disease. Cooley's anemia, thalassemia, and new Asian immigrants. Ann N Y Acad Sci 1998; 850:509.
- Garofalo F, Piga A, Lala R, et al. Bone metabolism in thalassemia. Ann N Y Acad Sci 1998; 850:475.
- SEVERE THALASSEMIA IN THE DEVELOPED WORLD
- EFFECTIVE CONTROL OF THALASSEMIA
- Individual patients
- - Hematopoietic cell transplantation
- - Improved diagnostic and screening methods
- - Oral iron chelating agents
- Biological problems
- Financial problems
- Community-wide problems
- - Genetic counseling of couples
- Ethical issues
- IMMIGRATION PATTERNS AND PROVISION OF HEALTH CARE
- Physician education
- Translators and nurse practitioners
- Community educational programs
- Examples of effective community action
- - Greece
- - Italy
- - Cyprus
- - China
- - Other countries
- COMPONENTS OF A SUCCESSFUL PROGRAM
- SUMMARY AND RECOMMENDATIONS