if the person has stunted growth, presence of extramedullary erythropoiesis (pediatrics), if a person is pregnant, and heart health. blood transfusions come with risks including making iron overload worse, the risk of infections, risk of red blood cell antibody formation, increased risk of the development of hypersensitivity reactions, and the risk of gall bladder inflammation (cholecystitis). multiple blood transfusions may result in iron overload. the iron overload related to thalassemia may be treated by chelation therapy with the medications deferoxamine, deferiprone, or deferasirox. these treatments have resulted in longer life expectancy for those with thalassemia major. deferoxamine is only effective as a daily injection, complicating its long-term use. however, it is inexpensive and safe. 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. when comparing effectiveness, there is no evidence that deferasirox or deferiprone is superior, however, a long term comparison has not been performed. deferasirox is not effective for all patients and may not be suitable for those with significant cardiac issues related to iron overload, while deferiprone appears to be the most effective agent when the heart is involved. furthermore, the cost of deferasirox is also significant. combining calcium channel blocker medications with iron chelation therapy is under study, however, the benefits are not clear from clinical trials conducted. growth hormone therapy there is some evidence that growth hormone replacement therapy may help to increase the rate at which children with thalassemia grow taller. bone-marrow transplantation bone-marrow transplantation may offer the possibility of a cure in young people who have an hla-matched donor. success rates have reached the 80–90% range. mortality from the procedure is about 3%. there are no randomized controlled trials that have tested the safety and efficacy of non-identical donor bone-marrow transplantation in persons with β- thalassemia who are dependent on blood transfusion. graft-versus-host diseases (gvhd) are one relevant side effect of bone-marrow transplantation. further research is necessary to evaluate whether mesenchymal stromal cells can be used as prophylaxis or treatment for gvhd. if the person does not have an hla-matched compatible donor, bone-marrow transplantation from haploidentical mother to child (mismatched donor) may be attempted. in a study of 31 people, the thalassemia-free survival rate was 70%, rejection 23% and mortality 7%. the most positive results tend to occur with very young people. other treatments many treatments are being investigated with the goal of reducing the number of blood transfusions that a person requires. foetal haemoglobin (hbf) inducer medications have been trialed with the goal of increasing hemoglobin and decreasing the person's reliance of a blood transfusion, however, the benefits are not clear and early results do not show a clinically meaningful benefit. hydroxyurea treatment with the goal of reactivating gamma‐genes to produce hbf also does not have any high quality evidence supporting its effectiveness. there is no evidence from randomized controlled trials to support zinc supplementation for those with thalassemia. computer programs or mobile applications have been suggested as tools to help people manage thalassemia and follow their therapies including iron chelation therapy. the effectiveness of these applications has not been well investigated. people with thalassemia are at a higher risk of osteoporosis. treatment options include bisphosphonates and sometimes the addition of hormonal therapy. other treatments have been suggested including calcitonin, zinc, hydroxyurea, and calcium supplementation. the effectiveness of bisphosphonates and zinc is not clear and further studies are required. dental care helping people with thalassemia with dental care and treating dental problems can be challenging due to the underlying condition. overload of iron due to blood transfusions may lead to iron deposition in the teeth and discolouration, and there is an increased risk for infection. treatment options for people with thalassemia need to be modified to ensure that the needs of the person are considered and early detection and early management of any problems is strongly suggested in order to reduce the risk of the person needing more complicated dental treatments. the evidence supporting the effectiveness of dental treatments on people with thalassemia is weak and higher quality clinical trials are needed. mild thalassemia people with thalassemia traits do not require medical or follow-up care after the initial diagnosis is made. people with β-thalassemia trait should be warned that their condition can be misdiagnosed as the more common iron-deficiency anemia. they should avoid routine use of iron supplements, but iron deficiency may develop during pregnancy or from chronic bleeding. genetic counseling is indicated for all persons with genetic disorders, especially when the family is at risk of a severe form of disease that may be prevented. prevention the american college of obstetricians and gynecologists recommends all people thinking of becoming pregnant be tested to see if they have thalassemia. genetic counseling and genetic testing are recommended for families who carry a thalassemia trait. 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. greece also has a screening program to identify people who are carriers. 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. 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. epidemiology the beta form of thalassemia is particularly prevalent among mediterranean peoples, and this geographical association is responsible for its original name. thalassemia resulted in 25,000 deaths in 2013 down from 36,000 deaths in 1990. 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. the disease is also found in populations living in africa, the americas, and in tharu people in the terai region of nepal and india. it is believed to account for much lower rates of malaria illnesses and deaths, 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. the estimated prevalence is 16% in people from cyprus, 1% 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. 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. because of the prevalence of the disease in countries with little knowledge of thalassemia, access to proper treatment and diagnosis can be difficult. 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. etymology and synonym the word thalassemia (/θælɪˈsiːmiə/) derives from the greek thalassa (θάλασσα), "sea", and neo-latin -emia (from the greek compound stem -aimia (-αιμία), from haima (αἷμα), "blood"). 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.: 877 research gene therapy gene therapy is being studied for thalassemia. the procedure involves collecting hematopoietic stem cells (hscs) from the affected person's blood. the hscs then have a beta-globin gene added using a lentiviral vector. after destroying the affected person's bone marrow with a dose of chemotherapy (a myeloablative conditioning regimen), the altered hscs are infused back into the affected person where they become engrafted in the bone marrow where they proliferate. this potentially results in a progressive increase in hemoglobin a2 synthesis in all subsequent developing red blood cells, with resultant resolution of the anemia. while one person with beta thalassemia has no longer required blood transfusions following treatment within a research trial, it is not an approved treatment as of 2018. hbf induction hbf induction is an attempt to reactivate fetal globin gene transcription. efforts involve trying to disrupt the fetal globin gene promoter.