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 thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.HBB blockage over time leads to decreased beta-chain synthesis. The bodys inability to construct new beta-chains leads to the underproduction of HbA (adult hemoglobin). Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. Repeated blood transfusions cause severe problems associated with iron overload. Signs and symptoms
Three main forms have been described: thalassemia minor, thalassemia intermedia, and thalassemia major which vary from asymptomatic or mild symptoms to severe anemia requiring lifelong transfusions. Individuals with beta thalassemia major (those who are homozygous for thalassemia mutations, or inheriting 2 mutations) usually present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, prenatal screening is very important.