Thalassemia

The word thalassemia ({{IPAc-en|θ|æ|l|ᵻ|ˈ|s|iː|m|i|ə}}) derives from the Greek thalassa (θάλασσα), "sea",{{LSJ|qa/lassa|θάλασσα|ref}}. and Neo-Latin -emia (from the Greek compound stem -aimia (-αιμία), from haima (αἷμα), "blood").{{LSJ|ai({{=}}ma|αἷμα|shortref}}. It was coined because the condition called "Mediterranean anemia" was first described in people of Mediterranean ethnicities. "Mediterranean anemia" was renamed thalassemia major once the genetics were better understood. The word thalassemia was first used in 1932.{{cite book |title=Wintrobe's Clinical Hematology |vauthors=Greer JP, Arber DA, Glader B, List AF, Means Jr RT, Paraskevas F, Rodgers GM, Foerster J |date=2013 |publisher=Wolters Kluwer, Lippincott Williams & Wilkins Health |isbn=978-1-4511-7268-3}}{{rp|877}}{{cite journal |vauthors=Whipple GH, Bradford WI |date=1932 |title=Racial or Familial Anemia of Children Associated With Fundamental Disturbances of Bone and Pigment Metabolism (Cooley-Von Jaksch) |journal=American Journal of Diseases of Children |volume=44 |pages=336–365 |doi=10.1001/archpedi.1932.01950090074009}}

File:1904_Hemoglobin.jpg

Normal human hemoglobins are tetrameric proteins composed of two pairs of globin chains, each of which contains one alpha-like (α-like) chain and one beta-like (β-like) chain. Each globin chain is associated with an iron-containing heme molecular component. Throughout life, the synthesis of the alpha-like and the beta-like chains is balanced so that their ratio is relatively constant and there is no excess of either type.Weatherall DJ. The New Genetics and Clinical Practice, Oxford University Press, Oxford 1991.

The specific alpha and beta-like chains that are incorporated into hemoglobins are highly regulated during development:

• Embryonic hemoglobins are expressed as early as four to six weeks of embryogenesis and disappear around the eighth week of gestation as they are replaced by fetal hemoglobin.Huisman TH. The structure and function of normal and abnormal haemoglobins. In: Baillière's Clinical Haematology, Higgs DR, Weatherall DJ (Eds), W.B. Saunders, London 1993. p.1.Natarajan K, Townes TM, Kutlar A. Disorders of hemoglobin structure: sickle cell anemia and related abnormalities. In: Williams Hematology, 8th ed, Kaushansky K, Lichtman MA, Beutler E, et al. (Eds), McGraw-Hill, 2010. p.ch.48.
• Fetal hemoglobin (HbF) is produced from approximately eight weeks of gestation through to birth and constitutes approximately 80 percent of hemoglobin in the full-term neonate. It declines during the first few months of life and constitutes <1 percent of total hemoglobin by and past early childhood. HbF is composed of two alpha globins and two gamma globins (α2γ2).
• Adult hemoglobin (HbA) is produced at low levels through embryonic and fetal life and is the predominant hemoglobin in children by six months of age and onward; it constitutes 96-97% of total hemoglobin in individuals without a hemoglobinopathy. It is composed of two alpha globins and two beta globins (α2β2).{{cite web |date=17 April 2002 |title=Hemoglobinopathies |url=http://sickle.bwh.harvard.edu/hemoglobinopathy.html |access-date=2009-02-06 |website=Brigham and Women's Hospital}}
• Hemoglobin A2 (HbA2) is a minor adult hemoglobin that normally accounts for approximately 2.5-3.5% of total hemoglobin. It is composed of two alpha globins and two delta globins (α2δ2).

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Symptoms depend on the type and severity of thalassemia. Carriers of thalassemia genes may have no symptoms (thalassemia minor) or very mild symptoms with occasional crisis (thalassemia intermedia); individuals who are homozygous for the mutation have severe and life threatening symptoms (thalassemia major).{{Cite web |date=17 Nov 2021 |title=Thalassemia-Thalassemia - Symptoms & causes |url=https://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/syc-20354995 |access-date=2025-01-07 |website=Mayo Clinic |language=en}}

Alpha thalassemia major is generally fatal to the unborn child, as the absence of alpha globin means that zero functional hemoglobin is produced during gestation. Unmatched gamma globin chains cluster to form hemoglobin Bart's, which is ineffective at transporting oxygen. In this situation, a fetus will develop hydrops fetalis, a form of edema, which can be detected on prenatal ultrasound.{{Cite web | vauthors = Pondarre C |date=May 2021 |title=Orphanet: Hb Bart's hydrops fetalis |url=https://www.orpha.net/en/disease/detail/163596 |access-date=2025-01-22 |website=Orphanet}} The child will normally die before or shortly after birth, unless intrauterine blood transfusion is performed.{{Cite web |title=Pathophysiology of alpha thalassemia |url=http://www.uptodate.com/contents/pathophysiology-of-alpha-thalassemia |access-date=2016-08-30 |website=www.uptodate.com}} Less severe alpha thalassemia may affect growth and development.{{Cite web |title=Alpha Thalassemia in Children |url=https://www.cedars-sinai.org/health-library/diseases-and-conditions---pediatrics/a/alpha-thalassemia-in-children.html |access-date=2025-01-08 |website=Cedars-Sinai |language=en-US}}

Beta thalassemia symptoms typically begin to show during the first six months of life, as the body winds down production of fetal hemoglobin HbF. In a normal individual, this would be replaced by adult hemoglobin HbA.

If thalassemia is untreated or undetected in the infant, this can lead to developmental issues such as slowed growth, delayed puberty, bone abnormalities, and intellectual impairment.{{Cite web | vauthors = Hanna R |date=6 March 2022 |title=Thalassemias |url=https://my.clevelandclinic.org/health/diseases/14508-thalassemias#symptoms-and-causes |access-date=5 January 2025 |website=Cleveland Clinic}}

More generally, impaired production of hemoglobin causes anemia, resulting in tiredness and a general lack of energy, shortness of breath, rapid or irregular heartbeat, dizziness, pale skin, yellowing of the skin and eyes (jaundice).{{Cite web |date=2017-10-24 |title=Thalassaemia - Symptoms |url=https://www.nhs.uk/conditions/thalassaemia/symptoms/ |access-date=2025-01-05 |website=National Health Service |language=en}}{{Cite web |last=CDC |date=2024-05-22 |title=About Thalassemia |url=https://www.cdc.gov/thalassemia/about/index.html |access-date=2025-01-05 |website=Centers for Disease Control and Prevention |language=en-us}}

In thalassemia, ineffective erythropoiesis causes the bone marrow to expand. This expansion is a compensatory response to the damage caused to red blood cells by the imbalanced production of globin chains.{{cite journal | vauthors = Piga A | title = Impact of bone disease and pain in thalassemia | journal = Hematology. American Society of Hematology. Education Program | volume = 2017 | issue = 1 | pages = 272–277 | date = December 2017 | pmid = 29222266 | pmc = 6142535 | doi = 10.1182/asheducation-2017.1.272 }} Bone marrow expansion can lead to abnormal bone structure, particularly in the skull and face. Expansion of the bone marrow in the developing child leads to a distinctive facial shape often referred to as "Chipmunk facies".{{cite journal | vauthors = Karakas S, Tellioglu AM, Bilgin M, Omurlu IK, Caliskan S, Coskun S | title = Craniofacial Characteristics of Thalassemia Major Patients | journal = The Eurasian Journal of Medicine | volume = 48 | issue = 3 | pages = 204–208 | date = October 2016 | pmid = 28149147 | pmc = 5268604 | doi = 10.5152/eurasianjmed.2016.150013 }} Other skeletal changes include osteoporosis, growth retardation, and malformation of the spine.{{Cite web |date=5 January 2025 |title=What Is Thalassemia? |url=https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/thalassemias |access-date=5 January 2025 |website=Penn Medicine, Philadelphia, PA}}

People with thalassemia can get too much iron in their bodies, either from the disease itself as RBCs are destroyed, or as a consequence of frequent blood transfusions. Excess iron is not excreted, but forms toxic non-transferrin-bound iron.{{cite journal | vauthors = Angoro B, Motshakeri M, Hemmaway C, Svirskis D, Sharma M | title = Non-transferrin bound iron | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 531 | pages = 157–167 | date = June 2022 | pmid = 35398023 | doi = 10.1016/j.cca.2022.04.004 }} This can lead to organ damage, potentially affecting the heart, liver, endocrine system, bones and spleen. Symptoms include an irregular heartbeat, cardiomyopathy, cirrhosis of the liver, hypothyroidism, delayed puberty and fertility problems, brittle and deformed bones, and an enlarged spleen.{{Cite web |date=January 2016 |title=Endocrine Problems in Thalassemia |url=https://www.swbh.nhs.uk/wp-content/uploads/2012/07/Endoctorine-Problems-in-Thalassemia_ML5090.pdf |website=Sandwell and West Birmingham NHS Trust}}{{Cite web |date=25 Oct 2023 |title=Thalassaemia |url=https://111.wales.nhs.uk/thalassaemia/ |access-date=8 Jan 2025 |website=Wales Ambulance Service NHS Trust}}

The spleen is the organ which removes damaged red blood cells from circulation; in thalassemia patients it is abnormally active, causing it to enlarge and possibly become hyperactive, a condition called hypersplenism.{{Cite web | vauthors = Martin M, Butler C |date=September 2022 |title=Thalassemia and the Spleen |url=https://www.thalassemia.org/wp-content/uploads/2022/09/Spleen.pdf |website=Cooley's Anemia Foundation}}

The immune system can become compromised in a number of ways; anemia, iron overload, and hypersplenism may affect the immune response and increase the risk of severe infection.{{cite journal | vauthors = Ricerca BM, Di Girolamo A, Rund D | title = Infections in thalassemia and hemoglobinopathies: focus on therapy-related complications | journal = Mediterranean Journal of Hematology and Infectious Diseases | volume = 1 | issue = 1 | pages = e2009028 | date = December 2009 | pmid = 21415996 | pmc = 3033166 | doi = 10.4084/MJHID.2009.028 | doi-broken-date = 14 January 2025 }}

File:Worldwide distribution of hemoglobinopathies.jpg

Having a mild form of alpha thalassemia has been demonstrated to protect against malaria and thus can be an advantage in malaria endemic areas, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), and perpetuating the mutation.{{cite journal | vauthors = Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN | title = The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya | journal = PLOS Medicine | volume = 3 | issue = 5 | pages = e158 | date = May 2006 | pmid = 16605300 | pmc = 1435778 | doi = 10.1371/journal.pmed.0030158 | doi-access = free }} There are suggestions that mild beta thalassemia may provide similar protection but this has not been proven.{{cite journal | vauthors = Willcox M, Björkman A, Brohult J, Pehrson PO, Rombo L, Bengtsson E | title = A case-control study in northern Liberia of Plasmodium falciparum malaria in haemoglobin S and beta-thalassaemia traits | journal = Annals of Tropical Medicine and Parasitology | volume = 77 | issue = 3 | pages = 239–246 | date = June 1983 | pmid = 6354114 | doi = 10.1080/00034983.1983.11811704 }}{{cite journal | vauthors = Introini V, Marin-Menendez A, Nettesheim G, Lin YC, Kariuki SN, Smith AL, Jean L, Brewin JN, Rees DC, Cicuta P, Rayner JC, Penman BS | title = The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion | journal = Scientific Reports | volume = 12 | issue = 1 | page = 8934 | date = May 2022 | pmid = 35624125 | doi = 10.1038/s41598-022-12060-4 | pmc = 9142571 | bibcode = 2022NatSR..12.8934I }}

α thalassemia genes have a high prevalence in populations of sub-Saharan Africa, Mediterranean, Middle East, and southeast and east Asia. β-thalassemias are commonest in the populations of the Mediterranean, Middle East, and Southeast Asia.{{cite journal | vauthors = Kattamis A, Forni GL, Aydinok Y, Viprakasit V | title = Changing patterns in the epidemiology of β-thalassemia | journal = European Journal of Haematology | volume = 105 | issue = 6 | pages = 692–703 | date = December 2020 | pmid = 32886826 | pmc = 7692954 | doi = 10.1111/ejh.13512 }}{{cite journal | vauthors = Williams TN, Weatherall DJ | title = World distribution, population genetics, and health burden of the hemoglobinopathies | journal = Cold Spring Harbor Perspectives in Medicine | volume = 2 | issue = 9 | pages = a011692 | date = September 2012 | pmid = 22951448 | pmc = 3426822 | doi = 10.1101/cshperspect.a011692 }}

{{Main|Alpha-thalassemia}}

{{Main|Beta-thalassemia}}

β-globin chains are encoded by the HBB gene on chromosome 11;{{OMIM|141900|Hemoglobin—Beta Locus; HBB}} in a healthy person with two copies on each chromosome, two loci encode the β chain. In beta thalassemia, a single faulty gene can be either asymptomatic or cause mild disease; if both genes are faulty this causes moderate to severe disease.{{cite journal | vauthors = Thein SL | title = The molecular basis of β-thalassemia | journal = Cold Spring Harbor Perspectives in Medicine | volume = 3 | issue = 5 | pages = a011700 | date = May 2013 | pmid = 23637309 | pmc = 3633182 | doi = 10.1101/cshperspect.a011700 }}

Mutated alleles are called β⁺ when partial function is conserved and some beta-globin is generated, or β^o when no functioning protein is produced.

The situation of both alleles determines the clinical picture:{{Cite web | vauthors = Shakeel H |date=25 March 2023 |title=Thalassaemia — Knowledge Hub |url=https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/thalassaemia/ |access-date=2025-01-13 |website=Genomics Education Programme and NHS England. |language=en}}

• β thalassemia major (Mediterranean anemia or Cooley anemia) is caused by a β^o/β^o genotype. No functional β chains are produced, and thus no hemoglobin A can be assembled. This is the most severe form of β-thalassemia.
• β thalassemia intermedia is caused by a β⁺/β^o or β⁺/β⁺ genotype. In this form, some hemoglobin A is produced.
• β thalassemia minor is caused by a β/β^o or β/β⁺ genotype. Only one of the two β globin alleles contains a mutation, so β chain production is not terribly compromised and patients may be relatively asymptomatic.

{{Main|Delta-thalassemia}}

As well as alpha and beta chains present in hemoglobin, about 3% of adult hemoglobin is made of alpha and delta globin chains. Just as with beta thalassemia, mutations that affect the ability of this gene to produce delta chains can occur.{{cite web|title=Delta-beta-thalassemia|url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=231237|website=Orphanet|access-date=16 September 2016}}{{cite web|title=HBD - hemoglobin subunit delta|url=http://www.orpha.net/consor/cgi-bin/Disease_Genes.php?lng=EN&data_id=20551&MISSING%20CONTENT=hemoglobin-subunit-delta&search=Disease_Genes_Simple&title=hemoglobin-subunit-delta|website=Orphanet|access-date=17 September 2016}}

A combination hemoglobinopathy occurs when someone inherits two different abnormal hemoglobin genes. If these are different versions of the same gene, one having been inherited from each parent it is an example of compound heterozygosity.

Both alpha- and beta- thalassemia can coexist with other hemoglobinopathies. Combinations involving alpha thalassemia are generally benign.{{cite journal | vauthors = Khatri G, Sahito AM, Ansari SA | title = Shared molecular basis, diagnosis, and co-inheritance of alpha and beta thalassemia | journal = Blood Research | volume = 56 | issue = 4 | pages = 332–333 | date = December 2021 | pmid = 34776416 | pmc = 8721464 | doi = 10.5045/br.2021.2021128 }}{{cite journal | vauthors = Wambua S, Mwacharo J, Uyoga S, Macharia A, Williams TN | title = Co-inheritance of alpha+-thalassaemia and sickle trait results in specific effects on haematological parameters | journal = British Journal of Haematology | volume = 133 | issue = 2 | pages = 206–209 | date = April 2006 | pmid = 16611313 | pmc = 4394356 | doi = 10.1111/j.1365-2141.2006.06006.x }}

Some examples of clinically significant combinations involving beta thalassemia include:

• Hemoglobin C/ beta thalassemia: common in Mediterranean and African populations generally results in a moderate form of anemia with splenomegaly.{{Cite web |date=February 2011 |title=Hemoglobin C |url=https://doh.wa.gov/sites/default/files/legacy/Documents/5220/HbCFactSheet.pdf |website=Washington State Department of Health}}
• Hemoglobin D/ beta thalassemia: common in the northwestern parts of India and Pakistan (Punjab region).{{cite journal |vauthors=Torres Lde S |date=March 2015 |title=Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis |journal=Revista Brasileira de Hematologia e Hemoterapia |volume=37 |issue=2 |pages=120–126 |doi=10.1016/j.bjhh.2015.02.007 |pmc=4382585 |pmid=25818823}}

• Hemoglobin E/ beta thalassemia: common in Cambodia, Thailand, and parts of India, it is clinically similar to β thalassemia major or β thalassemia intermedia.{{cite journal | vauthors = Olivieri NF, Muraca GM, O'Donnell A, Premawardhena A, Fisher C, Weatherall DJ | title = Studies in haemoglobin E beta-thalassaemia | journal = British Journal of Haematology | volume = 141 | issue = 3 | pages = 388–397 | date = May 2008 | pmid = 18410572 | doi = 10.1111/j.1365-2141.2008.07126.x }}
• Hemoglobin S/ beta thalassemia: common in African and Mediterranean populations, it is clinically similar to sickle-cell anemia.{{Cite web | vauthors = Gerber GF |date=April 2024 |title=Hemoglobin S–Beta-Thalassemia Disease - Hematology and Oncology |url=https://www.msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/hemoglobin-s-beta-thalassemia-disease |access-date=2024-12-24 |website=MSD Manual Professional Edition |language=en}}
• Delta-beta thalassemia is a rare form of thalassemia in which there is a reduced production of both the delta and beta globins. It is generally asymptomatic.{{cite book | vauthors = Pal GK |url=https://books.google.com/books?id=XpUAihQ7Ib4C&q=microcytosis+definition&pg=PA53 |title=Textbook Of Practical Physiology | edition = 2nd |date=2005 |publisher=Orient Blackswan |isbn=978-81-250-2904-5 |page=53 |language=en |access-date=17 September 2016}}

Checking for hemoglobinopathies begins during pregnancy, with a prenatal screening questionnaire which includes, among other things, a consideration of health issues in the child's parents and close relatives. During pregnancy, genetic testing can be done on samples taken of fetal blood, of amniotic fluid, or chorionic villus sampling.Colah, R. B., Gorakshakar, A. C., & Nadkarni, A. H. (2011). Invasive & non-invasive approaches for prenatal diagnosis of haemoglobinopathies: experiences from India. The Indian Journal of Medical Research, 134(4), 552–560.{{Cite web | vauthors = Ghidini A |date=19 March 2024 |title=Fetal blood sampling |url=https://www.uptodate.com/contents/fetal-blood-sampling |access-date=2025-01-13 |website=UpToDate, Inc.}} A routine heel prick test, in which a small sample of blood is collected a few days after birth, can detect some forms of hemoglobinopathy.{{Cite web |date=5 September 2024 |title=Newborn blood spot test |url=https://www.nhs.uk/conditions/baby/newborn-screening/blood-spot-test/ |access-date=2024-11-20 |website=National Health Service |language=en}}

File:0264Thalassemia.tif, small lymphocyte, platelets and monocyte are also present.]]The initial tests for thalassemias are:

• Complete blood count (CBC): Checks the number, size, and maturity of blood cells. Hemoglobin of less than 10 g/dl may indicate a carrier, below 7 g/dl is indicative of thalassemia major. In thalassemia major, mean corpuscular volume (MCV) are less than 70 fl, in thalassemia intermedia, MCV levels are below 80 fl (The normal range for MCV is 80–100 fl).{{cite book | vauthors = Bajwa H, Basit H | chapter = Thalassemia |date=August 2023 | title = StatPearls | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK545151/ |access-date=2025-01-13 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31424735 }} The Mentzer index can be a pointer for diagnosis of thalassemia; it can can be calculated from a CBC report.{{cite book |url=https://books.google.com/books?id=dlZDhbXDuOQC |title=Laboratory Hematology Practice |vauthors=Kottke-Marchant K, Davis B |publisher=John Wiley & Sons |year=2012 |isbn=978-1-4443-9857-1 |edition=1st |page=569}}
• Peripheral blood smear: A blood smear examined under a microscope can show red blood cells that are abnormal in shape (poikilocytosis or codocytes), color (hypochromic), or size (microcytic), as well as those with abnormal inclusions (Heinz bodies).
• Serum iron and ferritin: these tests are needed to rule out iron-deficiency anemia.

For an exact diagnosis, the following tests can be performed:

• Hemoglobin electrophoresis is a test that can detect different types of hemoglobin. Hemoglobin is extracted from the red cells, then introduced into a porous gel and subjected to an electrical field. This separates the normal and abnormal types of hemoglobin which can then be identified and quantified. Due to reduced production of HbA in beta thalassemia, the proportion of HbA2 and HbF relative to HbA are generally increased above normal. In alpha thalassemia the normal proportion is maintained.{{Cite web |title=Hemoglobin Electrophoresis: MedlinePlus Medical Test |url=https://medlineplus.gov/lab-tests/hemoglobin-electrophoresis/ |access-date=2024-11-20 |website=medlineplus.gov |language=en}}{{cite book | vauthors = Harewood J, Azevedo AM |chapter=Alpha Thalassemia |date=4 September 2023 | title = StatPearls |chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK441826/ |access-date=2025-01-13 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722856 }}
• High-performance liquid chromatography (HPLC) is reliable, fully automated, and able to distinguish most types of abnormal hemoglobin including carriers, The method separates and quantifies hemoglobin fractions by measuring their rate of flow through a column of absorbent material.{{cite journal | vauthors = Khera R, Singh T, Khuana N, Gupta N, Dubey AP | title = HPLC in characterization of hemoglobin profile in thalassemia syndromes and hemoglobinopathies: a clinicohematological correlation | journal = Indian Journal of Hematology & Blood Transfusion | volume = 31 | issue = 1 | pages = 110–115 | date = March 2015 | pmid = 25548455 | pmc = 4275515 | doi = 10.1007/s12288-014-0409-x }}
• DNA analysis using polymerase chain reaction (PCR) or next-generation sequencing. These tests can identify carriers of thalassemia genes and combination hemoglobinopathies, as well as identifying the exact mutation which underlies the disease.{{cite journal | vauthors = Munkongdee T, Chen P, Winichagoon P, Fucharoen S, Paiboonsukwong K | title = Update in Laboratory Diagnosis of Thalassemia | language = English | journal = Frontiers in Molecular Biosciences | volume = 7 | pages = 74 | date = 2020-05-27 | pmid = 32671092 | pmc = 7326097 | doi = 10.3389/fmolb.2020.00074 | doi-access = free }}

{{Main|Management of thalassemia}}

Treatment for thalassemia depends on the severity of the disease. People with thalassemia traits (thalassemia minor or non transfusion dependent thalassemia), may not require medical or follow-up care after the initial diagnosis is made.

{{Emedicine|article|958850|Pediatric Thalassemia|treatment}} Occasionally transfusions may be necessary particularly around childbirth, surgery, or if other conditions provoke anemia. A folic acid supplement may also be recommended.

For those with severe forms of thalassemia (thalassemia major, or transfusion-dependent thalassemia), the three principal treatments are red blood cell transfusions to relieve anemia, iron chelation to mitigate the side effects of transfusion, and folic acid supplementation to encourage the growth of new blood cells.{{Cite web |date=2018-01-25 |title=Treatment of Thalassemias |url=https://www.hoacny.com/patient-resources/blood-disorders/what-thalassemias/other-names-thalassemias/treatment-thalassemias |access-date=2025-01-17 |website=Hematology-Oncology Associates of CNY |language=en}} Other forms of treatment available depending on individual circumstances.

Blood transfusions are the main treatment approach for prolonging life. Donated healthy red blood cells have a functional life of 4 to 6 weeks before they wear out and are broken down in the spleen. Regular transfusions every three to four weeks are necessary in order to maintain hemoglobin at a healthy level. Transfusions come with risks including iron overload, the risk of acquiring infections, and the risk of immune reaction to the donated cells (alloimmunization).{{Cite web |last=CDC |date=2025-01-02 |title=Treatment of Thalassemia |url=https://www.cdc.gov/thalassemia/treatment/index.html |access-date=2025-01-15 |website=Thalassemia |language=en-us}}{{Cite web | vauthors = Butler C |date=16 January 2025 |title=Transfusion Issues in Thalassemia |url=https://thalassemia.org/files/galleries/Transfusion.pdf |access-date=16 January 2025 |website=The Cooley’s Anemia Foundation}}

Multiple blood transfusions lead to severe iron overload, as the body eventually breaks down the hemoglobin in donated cells. This releases iron which it is unable to excrete. Iron overload may be treated by chelation therapy with the medications deferoxamine, deferiprone, or deferasirox.{{Cite web |date=17 October 2022 |title=Thalassaemia - Treatment |url=https://www.nhs.uk/conditions/thalassaemia/treatment/ |access-date=2025-01-15 |website=nhs.uk |language=en}} Deferoxamine is only effective as a daily injection, complicating its long-term use. Adverse effects include primary skin reactions around the injection site and hearing loss. Deferasirox and deferiprone are both oral medications, whose common side effects include nausea, vomiting and diarrhea.{{cite journal |vauthors=Neufeld EJ |year=2010 |title=Update on iron chelators in thalassemia |journal=Hematology. American Society of Hematology. Education Program |volume=2010 |pages=451–455 |doi=10.1182/asheducation-2010.1.451 |pmid=21239834 |doi-access=free}}

Folate is a B group vitamin which is involved in the manufacture of red blood cells. Folate supplementation, in the form of folic acid, is often recommended in thalassemia.

Luspatercept is a drug used to treat anemia in adults with β-thalassemia, it can improve the maturation of red blood cells and reduce the need for frequent blood transfusions. It is administered by injection every three weeks. Luspatercept was authorised for use in the US in 2019 and by the European Medicines Agency in 2020.{{cite journal | vauthors = Cappellini MD, Taher AT | title = The use of luspatercept for thalassemia in adults | journal = Blood Advances | volume = 5 | issue = 1 | pages = 326–333 | date = January 2021 | pmid = 33570654 | pmc = 7805339 | doi = 10.1182/bloodadvances.2020002725 }}

Hydroxyurea is another drug that can sometimes be administered to relieve anemia caused by beta-thalassemia. This is achieved, in part, by reactivating fetal haemoglobin production; however its effectiveness is uncertain.{{Cite web | vauthors = Tidy C |date=23 Feb 2023 |title=Thalassaemia |url=https://patient.info/allergies-blood-immune/thalassaemia-leaflet |access-date=2025-01-16 |website=Egton Medical Information Systems Limited |language=en}}{{cite journal | vauthors = Banan M | title = Hydroxyurea treatment in β-thalassemia patients: to respond or not to respond? | journal = Annals of Hematology | volume = 92 | issue = 3 | pages = 289–299 | date = March 2013 | pmid = 23318979 | doi = 10.1007/s00277-012-1671-3 }}{{cite journal | vauthors = Ansari SH, Lassi ZS, Khowaja SM, Adil SO, Shamsi TS | title = Hydroxyurea (hydroxycarbamide) for transfusion-dependent β-thalassaemia | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD012064 | date = March 2019 | pmid = 30882896 | pmc = 6421980 | doi = 10.1002/14651858.CD012064.pub2 | collaboration = Cochrane Cystic Fibrosis and Genetic Disorders Group }}

People with thalassemia are at a higher risk of osteoporosis. Treatment options include bisphosphonates and zinc supplementation.{{cite journal | vauthors = Bhardwaj A, Swe KM, Sinha NK | title = Treatment for osteoporosis in people with beta-thalassaemia | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD010429 | date = May 2023 | pmid = 37159055 | pmc = 10167785 | doi = 10.1002/14651858.CD010429.pub3 }}

File:Spleen_after_spleenectomy.jpg

The spleen is the organ which removes damaged or misshapen red blood cells from the circulation. In thalassemia, this can lead to the spleen becoming enlarged, a condition known as splenomegaly. Slight enlargement of the spleen is not a problem, however if it becomes extreme then surgical removal of the spleen (splenectomy) may be recommended.

Hematopoietic stem cells (HSC) are cells in the bone marrow that can develop into all types of blood cells, including red blood cells, white blood cells, and platelets.{{Cite web |date=December 12, 2022 |title=Hematopoiesis |url=https://my.clevelandclinic.org/health/articles/24287-hematopoiesis |access-date=6 December 2024 |website=Cleveland Clinic}} There are two possible ways to treat hemoglobinopathies by targeting HSCs. One is to transplant HSCs from a healthy donor into the patient's bone marrow; this was pioneered in 1981. More recently, it has become possible to use CRISPR gene editing technology to modify the patient's own HSCs in a way that increases production of functional beta-globin chains, leading to near normal levels of healthy hemoglobin.{{cite journal | vauthors = Olson TS, Walters MC | title = Allogeneic haematopoietic stem-cell transplantation versus gene therapy for haemoglobinopathies | language = English | journal = The Lancet. Haematology | volume = 10 | issue = 10 | pages = e798-e800 | date = October 2023 | pmid = 37793770 | doi = 10.1016/S2352-3026(23)00246-6 }}

All stem cell treatments must involve myeloablation of the patients' bone marrow in order to remove HSCs containing the faulty gene. This requires high doses of chemotherapy agents with side effects such as sickness and tiredness. A long hospital stay is necessary after infusion of the replacement HSCs while the cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin.{{Cite web |date=2017-10-23 |title=Stem cell transplant - What happens |url=https://www.nhs.uk/conditions/stem-cell-transplant/what-happens/ |access-date=2024-12-07 |website=nhs.uk |language=en}}

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for both alpha and beta thalassemia. It involves replacing the dysfunctional stem cells in the bone marrow with healthy cells from a well-matched donor. Cells are ideally sourced from human leukocyte antigen matched relatives; the procedure is more likely to succeed in children rather than adults.{{Cite web |date=2023-11-10 |title=NHS England » Clinical commissioning policy: allogeneic haematopoietic stem cell transplantation (Allo-HSCT) for adult transfusion dependent thalassaemia |url=https://www.england.nhs.uk/publication/clinical-commissioning-policy-allogeneic-haematopoietic-stem-cell-transplantation/ |access-date=2025-01-18 |website=www.england.nhs.uk |language=en-US}}{{cite journal | vauthors = Lucarelli G, Isgrò A, Sodani P, Gaziev J | title = Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia | journal = Cold Spring Harbor Perspectives in Medicine | volume = 2 | issue = 5 | pages = a011825 | date = May 2012 | pmid = 22553502 | pmc = 3331690 | doi = 10.1101/cshperspect.a011825 }}

The first HSC transplant for thalassemia was carried out in 1981 on a patient with beta thalassemia major. Since then, a number of patients have received bone marrow transplants from healthy matched donors, although this procedure has a high level of risk.{{cite journal | vauthors = Angelucci E, Pilo F, Targhetta C, Pettinau M, Depau C, Cogoni C, Usai S, Pani M, Dessì L, Baronciani D | title = Hematopietic stem cell transplantation in thalassemia and related disorders | journal = Mediterranean Journal of Hematology and Infectious Diseases | volume = 1 | issue = 1 | pages = e2009015 | date = December 2009 | pmid = 21415993 | pmc = 3033161 | doi = 10.4084/MJHID.2009.015 }}

In 2018 an unborn child with hydrops fetalis, a potentially fatal complication of alpha thalassemia, was successfully transfused in utero with her mother's stem cells.{{Cite web | vauthors = Leigh S |date=2018-05-25 |title=Baby Born in World's First In Utero Stem Cell Transplant Trial {{!}} UC San Francisco |url=https://www.ucsf.edu/news/2018/05/410436/baby-born-worlds-first-utero-stem-cell-transplant-trial |access-date=2025-01-20 |website=University of California San Francisco |language=en}}

HSCT is a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. Risks associated with HSCT can include graft-versus host disease, failure of the graft, and other toxicity related to the transplant.{{cite journal | vauthors = Rotin LE, Viswabandya A, Kumar R, Patriquin CJ, Kuo KH | title = A systematic review comparing allogeneic hematopoietic stem cell transplant to gene therapy in sickle cell disease | journal = Hematology | volume = 28 | issue = 1 | pages = 2163357 | date = December 2023 | pmid = 36728286 | doi = 10.1080/16078454.2022.2163357 | doi-access = free }} In one study of 31 people, the procedure was successful for 22 whose hemoglobin levels improved to the normal range, in seven the graft failed and they continued to live with thalassemia, and two died of transplantation-related causes.{{cite journal | vauthors = Sodani P, Isgrò A, Gaziev J, Paciaroni K, Marziali M, Simone MD, Roveda A, De Angelis G, Gallucci C, Torelli F, Isacchi G, Zinno F, Landi F, Adorno G, Lanti A, Testi M, Andreani M, Lucarelli G | title = T cell-depleted hla-haploidentical stem cell transplantation in thalassemia young patients | journal = Pediatric Reports | volume = 3 Suppl 2 | issue = Suppl 2 | pages = e13 | date = June 2011 | pmid = 22053275 | pmc = 3206538 | doi = 10.4081/pr.2011.s2.e13 }}

Gene therapy for hemoglobinopathies was first trialled in 2014 on a single patient with sickle cell disease (a fault in the beta globin gene),{{cite journal | vauthors = Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chrétien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M | title = Gene Therapy in a Patient with Sickle Cell Disease | journal = The New England Journal of Medicine | volume = 376 | issue = 9 | pages = 848–855 | date = March 2017 | pmid = 28249145 | doi = 10.1056/NEJMoa1609677 }} and followed by clinical trials in which a number of patients with either sickle cell or beta thalassemia were successfully treated.{{cite web |date=5 December 2020 |title=CRISPR and another genetic strategy fix cell defects in two common blood disorders |url=https://www.science.org/content/article/crispr-and-another-genetic-strategy-fix-cell-defects-two-common-blood-disorders |access-date=7 December 2020 |website=ScienceMag.org |publisher=Science |quote="... teams report that two strategies for directly fixing malfunctioning blood cells have dramatically improved the health of a handful of people with these genetic diseases." |vauthors=Kaiser J}}

Gene therapies work by first harvesting the patient's HSCs, then using CRISPR gene editing to modify their DNA in the laboratory. In parallel with this, the person with thalassemia disease undergoes a myeloablation procedure (a form of chemotherapy) to destroy the remaining HSCs in their bone marrow. The laboratory treated cells are then infused back into the patient where they colonise the bone marrow and eventually commence production of healthy blood cells. There are fewer risks from this procedure than from HSCT, since the transplanted cells are autologous having originated from the patient herself/himself. {{cite journal | vauthors = Biffi A | title = Gene Therapy as a Curative Option for β-Thalassemia | journal = The New England Journal of Medicine | volume = 378 | issue = 16 | pages = 1551–1552 | date = April 2018 | pmid = 29669229 | doi = 10.1056/NEJMe1802169 }}

There are two approved forms of gene therapy for beta thalassemia.{{cite web |date=17 August 2022 |title=Zynteglo |url=https://www.fda.gov/vaccines-blood-biologics/zynteglo |url-status=live |archive-url=https://web.archive.org/web/20220826182752/https://www.fda.gov/vaccines-blood-biologics/zynteglo |archive-date=26 August 2022 |access-date=26 August 2022 |website=U.S. Food and Drug Administration}}{{Cite web |date=14 Jan 2024 |title=CRISPR Therapeutics Announces U.S. Food and Drug Administration (FDA) Approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia |url=https://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-announces-us-food-and-drug-administration/ |access-date=20 January 2025 |website=CRISPR Therapeutics}}

Betibeglogene autotemcel, sold under the brand name Zynteglo, is a gene therapy for the treatment for beta thalassemia which adds a healthy beta-globin gene to the HSCs.{{cite journal |vauthors=Negre O, Eggimann AV, Beuzard Y, Ribeil JA, Bourget P, Borwornpinyo S, Hongeng S, Hacein-Bey S, Cavazzana M, Leboulch P, Payen E |date=February 2016 |title=Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene |journal=Human Gene Therapy |volume=27 |issue=2 |pages=148–165 |doi=10.1089/hum.2016.007 |pmc=4779296 |pmid=26886832}} It was approved for medical use in the United States in August 2022.{{cite press release |title=FDA Approves First Cell-Based Gene Therapy to Treat Adult and Pediatric Patients with Beta-thalassemia Who Require Regular Blood Transfusions |date=17 August 2022 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-treat-adult-and-pediatric-patients-beta-thalassemia-who |access-date=20 August 2022 |url-status=live |archive-url=https://web.archive.org/web/20220821044703/https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-treat-adult-and-pediatric-patients-beta-thalassemia-who |archive-date=21 August 2022 |website=U.S. Food and Drug Administration (FDA)}} {{PD-notice}} The procedure involves collecting hematopoietic stem cells (HSCs) from the affected person's blood. In the laboratory, these HSCs then have a new gene for T87Q-globin (a modified beta-globin) introduced to them using a lentiviral vector. Meanwhile the affected person undergoes myeloablative conditioning, after which the altered HSCs can be infused back, becoming engrafted in the bone marrow where they proliferate. This results in a progressive increase in beta-globin synthesis which improves the balance of alpha and beta globins in all subsequent developing red blood cells. Healthy hemoglobin A is generated resolving the anemia.

Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy for the treatment of transfusion-dependent beta thalassemia which induces increased production of fetal hemoglobin HbF.{{cite web |date=31 October 2023 |title=FDA advisers see no roadblocks for gene-editing treatment for sickle cell disease |url=https://www.npr.org/sections/health-shots/2023/10/31/1208041252/a-landmark-gene-editing-treatment-for-sickle-cell-disease-moves-closer-to-realit |url-status=live |archive-url=https://web.archive.org/web/20231204214937/https://www.npr.org/sections/health-shots/2023/10/31/1208041252/a-landmark-gene-editing-treatment-for-sickle-cell-disease-moves-closer-to-realit |archive-date=4 December 2023 |access-date=4 December 2023 |website=NPR |vauthors=Stein R}} The treatment was approved in the United Kingdom for the treatment of transfusion-dependent beta thalassemia in November 2023{{cite press release |title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia |date=16 November 2023 |url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |access-date=8 December 2023 |url-status=live |archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |archive-date=25 November 2023 |website=Medicines and Healthcare products Regulatory Agency (MHRA)}} and in the United States in January 2024. Casgevy works by editing the BCL11A gene, which normally inhibits the production of HbF in adults. The edit has the effect of increasing production of gamma globin, a component of fetal hemoglobin HbF, and thereby resolving the anemia.{{Cite web |title=Patient Information {{!}} CASGEVY® (exagamglogene autotemcel) |url=https://www.casgevy.com/beta-thalassemia |archive-url=http://web.archive.org/web/20241202201940/https://www.casgevy.com/beta-thalassemia |archive-date=2024-12-02 |access-date=2025-01-20 |website=www.casgevy.com |language=en}}

The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they have thalassemia.{{cite web |title=Carrier Screening in the Age of Genomic Medicine – ACOG |url=http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Genetics/Carrier-Screening-in-the-Age-of-Genomic-Medicine |url-status=live |archive-url=https://web.archive.org/web/20170225052721/http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Genetics/Carrier-Screening-in-the-Age-of-Genomic-Medicine |archive-date=25 February 2017 |access-date=24 February 2017 |website=www.acog.org}} Genetic counseling and genetic testing are recommended for families who carry a thalassemia trait.{{cite journal | vauthors = Hussein N, Henneman L, Kai J, Qureshi N | title = Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 10 | pages = CD010849 | date = October 2021 | pmid = 34634131 | pmc = 8504980 | doi = 10.1002/14651858.CD010849.pub4 | collaboration = Cochrane Cystic Fibrosis and Genetic Disorders Group }} Understanding the genetic risk, ideally before a family is started, would hopefully allow families to understand more about the condition and make an informed decision that is best for their family.

A screening policy exists in Cyprus to reduce the rate of thalassemia, which, since the program's implementation in the 1970s (also including prenatal screening and abortion), has reduced the number of children born with the disease from one of every 158 births to almost zero.{{cite journal | vauthors = Leung TN, Lau TK, Chung TK | title = Thalassaemia screening in pregnancy | journal = Current Opinion in Obstetrics & Gynecology | volume = 17 | issue = 2 | pages = 129–134 | date = April 2005 | pmid = 15758603 | doi = 10.1097/01.gco.0000162180.22984.a3 | s2cid = 41877258 }} Greece also has a screening program to identify people who are carriers.{{cite journal | vauthors = Loukopoulos D | title = Haemoglobinopathies in Greece: prevention programme over the past 35 years | journal = The Indian Journal of Medical Research | volume = 134 | issue = 4 | pages = 572–576 | date = October 2011 | pmid = 22089622 | pmc = 3237258 }}

In Iran as a premarital screening, the man's red cell indices are checked first. If he has microcytosis (mean cell hemoglobin < 27 pg or mean red cell volume < 80 fl), the woman is tested. When both are microcytic, their hemoglobin A2 concentrations are measured. If both have a concentration above 3.5% (diagnostic of thalassemia trait) they are referred to the local designated health post for genetic counseling.{{cite journal | vauthors = Samavat A, Modell B | title = Iranian national thalassaemia screening programme | journal = BMJ | volume = 329 | issue = 7475 | pages = 1134–1137 | date = November 2004 | pmid = 15539666 | pmc = 527686 | doi = 10.1136/bmj.329.7475.1134 }}

Large-scale awareness campaigns are being organized in India both by government and non-government organizations to promote voluntary premarital screening, with marriage between carriers strongly discouraged.{{cite journal | vauthors = Petrou M | title = Screening for beta thalassaemia | journal = Indian Journal of Human Genetics | volume = 16 | issue = 1 | pages = 1–5 | date = January 2010 | pmid = 20838484 | pmc = 2927788 | doi = 10.4103/0971-6866.64934 | doi-access = free }}

The beta form of thalassemia is particularly prevalent among Mediterranean peoples, and this geographical association is responsible for its original name. Thalassemias resulted in 25,000 deaths in 2013, down from 36,000 deaths in 1990.{{cite journal | vauthors = Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou MG, etal | collaboration = GBD 2013 Mortality and Causes of Death Collaborators | title = Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 | journal = Lancet | volume = 385 | issue = 9963 | pages = 117–171 | date = January 2015 | pmid = 25530442 | pmc = 4340604 | doi = 10.1016/S0140-6736(14)61682-2 | hdl = 11655/15525 }}

In Europe, the highest concentrations of the disease are found in Greece, coastal regions in Turkey (particularly the Aegean Region such as İzmir, Balıkesir, Aydın, Muğla, and Mediterranean Region such as Antalya, Adana, Mersin), in southern Spain, in parts of Italy, particularly southern Italy. With the exception of the Balearics, the major Mediterranean Islands, such as Sicily, Sardinia, Malta, Corsica, Cyprus, and Crete are heavily affected. Other Mediterranean peoples, as well as those in the vicinity of the Mediterranean, also have high rates of thalassemia, including people from North Africa and West Asia. Far from the Mediterranean, South Asians are also affected, with the world's highest concentration of carriers (16–18% of the population) in the Maldives.{{cite journal | vauthors = Waheed F, Fisher C, Awofeso A, Stanley D | title = Carrier screening for beta-thalassemia in the Maldives: perceptions of parents of affected children who did not take part in screening and its consequences | journal = Journal of Community Genetics | volume = 7 | issue = 3 | pages = 243–253 | date = July 2016 | pmid = 27393346 | pmc = 4960032 | doi = 10.1007/s12687-016-0273-5 }}

The disease is also found in populations living in Africa, the Americas, and in Tharu people in the Terai region of Nepal and India.{{cite journal | vauthors = Modiano G, Morpurgo G, Terrenato L, Novelletto A, Di Rienzo A, Colombo B, Purpura M, Mariani M, Santachiara-Benerecetti S, Brega A | title = Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population | journal = American Journal of Human Genetics | volume = 48 | issue = 2 | pages = 390–397 | date = February 1991 | pmid = 1990845 | pmc = 1683029 }} It is believed to account for much lower rates of malaria illnesses and deaths,{{cite journal | vauthors = Terrenato L, Shrestha S, Dixit KA, Luzzatto L, Modiano G, Morpurgo G, Arese P | title = Decreased malaria morbidity in the Tharu people compared to sympatric populations in Nepal | journal = Annals of Tropical Medicine and Parasitology | volume = 82 | issue = 1 | pages = 1–11 | date = February 1988 | pmid = 3041928 | doi = 10.1080/00034983.1988.11812202 }} accounting for the historic ability of Tharus to survive in areas with heavy malaria infestation while others could not. Thalassemias are particularly associated with people of Mediterranean origin, Arabs (especially Palestinians and people of Palestinian descent), and Asians.E. Goljan, Pathology, 2nd ed. Mosby Elsevier, Rapid Review Series.{{page needed|date=June 2013}} The estimated prevalence is 16% in people from Cyprus, 1%{{cite web |language=th |title=Thalassemia |date=September 2011 |publisher=Department of Medical Sciences |url=http://www.dmsc.moph.go.th/webrOOt/ri/Npublic/p04.htm |archive-url=https://web.archive.org/web/20110925075716/http://www.dmsc.moph.go.th/webroot/ri/Npublic/p04.htm |archive-date=25 September 2011}} in Thailand, and 3–8% in populations from Bangladesh, China, India, Malaysia and Pakistan.

Estimates suggest that approximately 1.5% of the global population (80 – 90 million people) are β-thalassemia carriers.{{cite journal | vauthors = Galanello R, Origa R | title = Beta-thalassemia | journal = Orphanet Journal of Rare Diseases | volume = 5 | issue = 1 | page = 11 | date = May 2010 | pmid = 20492708 | pmc = 2893117 | doi = 10.1186/1750-1172-5-11 | doi-access = free }} However, exact data on carrier rates in many populations are lacking, particularly in developing areas of the world known or expected to be heavily affected.{{cite journal | vauthors = Vichinsky EP | title = Changing patterns of thalassemia worldwide | journal = Annals of the New York Academy of Sciences | volume = 1054 | issue = 1 | pages = 18–24 | date = 1 November 2005 | pmid = 16339647 | doi = 10.1196/annals.1345.003 | s2cid = 26329509 | bibcode = 2005NYASA1054...18V }} Because of the prevalence of the disease in countries with little knowledge of thalassemia, access to proper treatment and diagnosis can be difficult.{{cite journal | vauthors = Weatherall DJ | title = Keynote address: The challenge of thalassemia for the developing countries | journal = Annals of the New York Academy of Sciences | volume = 1054 | issue = 1 | pages = 11–17 | date = November 2005 | pmid = 16339646 | doi = 10.1196/annals.1345.002 | s2cid = 45770891 | bibcode = 2005NYASA1054...11W }} While there are some diagnostic and treatment facilities in developing countries, in most cases these are not provided by government services and are available only to patients who can afford them. In general, poorer populations only have access to limited diagnostic facilities and blood transfusions. In some developing countries, there are virtually no facilities for diagnosis or management of thalassemia.

Rudolf Von Jaksch in 1889 first described “anaemia leucaemic infantum” as a form of chronic anemia in children which combined with an enlarged spleen, and abnormal size and shape of the red blood cells. His discovery was subsequently found to comprise a collection of different conditions.{{cite journal | vauthors = Siddiqui S, Steensma DP, Kyle RA | title = Thalassemia and Thomas Benton Cooley | language = English | journal = Mayo Clinic Proceedings | volume = 92 | issue = 11 | pages = e161-e162 | date = November 2017 | pmid = 29101943 | doi = 10.1016/j.mayocp.2017.06.024 }}

The first definitive identification of a thalassemia was in 1925 by Thomas Benton Cooley, an American pediatrician specialising in hematology and childhood anemias. Cooley noted similarities in symptoms of children in his care having Greek or Italian ancestry; he named it "erythroblastic anemia," but it became popularly known as Cooley's anemia (now termed beta thalassemia major).{{cite book |author=Stuart H. Orkin |title=Nathan and Oski's Hematology of Infancy and Childhood, Volume 1 |author2=David G. Nathan |author3=David Ginsburg |author4=A. Thomas Look |publisher=Elsevier Health Sciences |year=2009 |isbn=978-1-4160-3430-8 |pages=1054–1055}}

The term "thalassemia" was coined by George Whipple in 1932. The word "thalassemia" comes from the Greek word thalassa, which means "sea". The suffix "-emia" comes from the Greek word haima, which means "blood". The term was coined because the condition was strongly associated with people of Mediterranean descent.

In 1948, Italian researchers established that the type of thalassemia which was prevalent in Italy was inherited in a recessive pattern.{{Cite journal | vauthors = Greco F, Marino F |date=2022-04-28 |title=Editor's Pick: Social Impact and Quality of Life of Patients with β-Thalassaemia: A Systematic Review |url=https://www.emjreviews.com/hematology/article/social-impact-and-quality-of-life-of-patients-with-%ce%b2-thalassaemia-a-systematic-review-j060121/ |journal=EMJ Hematol Hematology 2022 |language=en-GB |doi=10.33590/emjhematol/22-00041 |issn=2053-6631|hdl=11383/2140214 |hdl-access=free }}{{cite journal | vauthors = De Simone G, Quattrocchi A, Mancini B, di Masi A, Nervi C, Ascenzi P | title = Thalassemias: from gene to therapy | journal = Molecular Aspects of Medicine | volume = 84 | pages = 101028 | date = April 2022 | pmid = 34649720 | doi = 10.1016/j.mam.2021.101028 | series = Hemoglobin and Myoglobin in their reactions with ligands }}

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{{refbegin}}

• {{cite journal | vauthors = De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M, Karimi M, Yassin MA, El Awwa A, Stoeva I, Raiola G, Galati MC, Bedair EM, Fiscina B, El Kholy M | title = Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines | journal = Indian Journal of Endocrinology and Metabolism | volume = 17 | issue = 1 | pages = 8–18 | date = January 2013 | pmid = 23776848 | pmc = 3659911 | doi = 10.4103/2230-8210.107808 | doi-access = free }}

{{refend}}

{{Reflist}}

{{Medical resources

| DiseasesDB = 448

| DiseasesDB_mult = {{DiseasesDB2|33334}}

| ICD11 = {{ICD11|3A50}}

| ICD10 = {{ICD10|D|56||d|56}}

| ICD9 = {{ICD9|282.4}}

| MedlinePlus = 000587

| eMedicineSubj = article

| eMedicineTopic = 958850

| eMedicine_mult = {{eMedicine2|article|206490}} {{eMedicine2|article|955496}} {{eMedicine2|article|396792}}

| MeshID = D013789

| OMIM = 141800

| OMIM_mult = {{OMIM|141850||none}} {{OMIM|142310||none}} {{OMIM|604131||none}} {{OMIM|141800||none}} {{OMIM|141850||none}} {{OMIM|142310||none}} {{OMIM|604131||none}}

| GeneReviewsNBK = NBK1435

| GeneReviewsName = Alpha-Thalassemia

| GeneReviewsNBK2 = NBK1426

| GeneReviewsName2 = Beta-Thalassemia

}}

• {{cite web | url = http://www.genome.gov/10001221 | title = Learning About Thalassemia | work = National Human Genome Research Institute | date = 27 December 2013 }}

{{Diseases of RBCs}}

Category:Autosomal recessive disorders

Category:Hereditary hemolytic anemias

Category:Disorders of globin and globulin proteins

Category:Wikipedia medicine articles ready to translate

Category:Mediterranean