ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production. on june 10, 2022, a u.s. federal advisory panel recommended that the fda approve a gene therapy treatment for use with beta thalassemia. the manufacturer bluebird bio charges $2.8 million in the united states for its one-time treatment zynteglo (betibeglogene autotemcel). gene editing therapies aimed at increasing fetal hemoglobin production in beta thalassemia as well as sickle cell anemia by inhibiting the bcl11a gene are also being explored. surgical patients with thalassemia major are more inclined to have a splenectomy. the use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. splenectomy is also associated with increased risk of infections and increased morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells. patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. the different surgical techniques are the open and laparoscopic method. the laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. if it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least one week (preferably three weeks) before the surgery. therapeutic long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9–10.5 g/dl (11-12 g/dl in those with concomitant heart disease). to ensure quality blood transfusions, the packed red blood cells should be leucoreduced. by having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. washed red cells have been removed of plasma proteins that would have become a target of the patient's antibodies allowing the transfusion to be carried out safely. cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. these regular transfusions promote normal growth, physical activities and suppress bone marrow hyperactivity. pharmaceutical during normal iron homeostasis the circulating iron is bound to transferrin. but with iron overload (such as with frequent blood transfusions), the ability for transferrin to bind iron is exceeded and non-transferrin bound iron accumulated. this unbound iron is toxic due to its high propensity to induce oxygen species and is responsible for cellular damage. the prevention of iron overload protects patients from morbidity and mortality. the primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. iron chelation is a medical therapy that may prevent the complications of iron overload. every unit of transfused blood contains 200–250 mg of iron and the body has no natural mechanism to remove excess iron. the excess iron can be removed by iron chelators (deferoxamine, deferiprone and deferasirox). luspatercept (ace-536) is a recombinant fusion protein that is used as a treatment in adults with transfusion dependent beta thalassemia. it consists of a modified extra-cellular domain of human activin receptor type iib bound to the fc portion of the human igg1 antibody. the molecule binds to select transforming growth factor beta superfamily ligands to block smad2 and 3 signaling, thus enhancing erythroid maturation. the medication has been shown to reduce the transfusion burden by 33% in adults with transfusion dependent beta thalassemia as compared to placebo and was also associated with decreased ferritin levels (with no significant decreases in liver or cardiac iron levels). beta thalassemia intermedia patients with beta thalassemia intermedia require no transfusions or may require episodic blood transfusions during certain circumstances (infection, pregnancy, surgery). patients with frequent transfusions may develop iron overload and require chelation therapy. transmission is autosomal recessive; however, dominant mutations and compound heterozygotes have been reported. genetic counseling is recommended and prenatal diagnosis may be offered. beta thalassemia minor patients with beta thalassemia minor are usually asymptomatic and are often monitored without treatment. beta thalassemia minor may coexist with other conditions such as chronic hepatitis b, chronic hepatitis c, non-alcoholic fatty liver disease and alcoholic liver disease that, when combined or co-existing, may cause a person to have iron overload of the liver and more severe liver disease. epidemiology the beta form of thalassemia is particularly prevalent among the mediterranean peoples and this geographical association is responsible for its naming: thalassa (θάλασσα) is the greek word for sea and haima (αἷμα) is the greek word for blood. in europe, the highest concentrations of the disease are found in greece and the turkish coastal regions. the major mediterranean islands (except the balearics) such as sicily, sardinia, corsica, cyprus, malta and crete are heavily affected in particular. other mediterranean peoples, as well as those in the vicinity of the mediterranean, also have high incidence rates, including people from west asia and north africa. the data indicate that 15% of the greek and turkish cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes. evolutionary adaptation the thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. in that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease. incidence the disorder is more prevalent in certain ethnicities and age groups. beta thalassemia is most prevalent in the "thalassemia belt" which includes areas in sub-saharan africa, the mediterranean extending into the middle east and southeast asia. this geographical distribution is thought to be due to beta-thalassemia carrier state (beta thalassemia minor) conferring a resistance to malaria. in the united states, thalassemia's prevalence is approximately 1 in 272,000 or 1,000 people. there have been 4,000 hospitalized cases in england in 2002 and 9,233 consultant episodes for thalassemia. men accounted for 53% of hospital consultant episodes and women accounted for 47%. the mean patient age is 23, with only 1% of consultants being older than 75, and 69% being 15–59. it is estimated that 1.5% of the world's population are carriers and 40,000 affected infants are born with the disease annually. beta thalassemia major is usually fatal in infancy if blood transfusions are not initiated immediately.