Thalessemia is ?

Thalessemia is a group of hereditary anemias caused by reduced synthesis of one of the globin chains that combine hemoglobin (HbA, A2, B2). Thalassemia is an inherited disorder syndrome and belongs to the hemoglobinopathy group, which is a disorder caused by impaired hemoglobin synthesis due to mutations in or near the globin gene. Children who experience thalassemia show signs and symptoms including weakness, physical development not according to age, weight loss, not being able to live without blood transfusions, changes in facial shape, anemia, enlarged spleen, facecoley, hepatomegaly.

Thalassemia Mayor, Thalassemia major is the most severe clinical condition of Thalassemia. Thalassemia major occurs because the hemoglobin encoding gene on 2 chromosomal alleles is abnormal. Patients need blood transfusions from the first year of growth in the age range of 6-24 months and continuously throughout their lives. The initial symptom is a pale state on the skin seen on the palms of the hands, eyes, inner eyelids, and abdominal area. and all skin surfaces. Thalassemia Minor It is referred to as a carrier of traits, traits, carrier of mutants, or career Thalassemia. Thalassemia's career did not show any clinical symptoms during her lifetime. Thalassemia intermedia It occurs due to abnormalities in 2 chromosomes that descend from the father and mother. The difference is in the type of mutant gene that is descended. Thalassemia major individuals decreased 2 mutant genes of the severe mutant type, while in Thalassemia intermediate, the 2 genes are a combination of heavy and mild mutants, tau mild mutants and mild mutants. (Andriyani, 2021) Cause According to (HASANAN, 2018) the cause of Thalassemia is due to the inability of the bone marrow to form the proteins needed to produce hemoglobin perfectly. Hemoglobin is an iron-rich protein that is located in red blood cells (erythrocytes) and functions to carry oxygen from the lungs to the rest of the body. This disease is a recessively inherited hereditary hemolytic anemia. It is characterized by a deficiency in globin production in hemoglobin. The occurrence of 12 damage to red blood cells in the blood vessels so that the lifespan of erythrocytes becomes short. The damage is due to abnormal hemoglobin.

Classification The classification of Thalassemia is divided into 3 namely: Thalassemia major In thalassemia major, the production of globin chains is disrupted, resulting in an imbalance in the synthesis of globin chains (alpha>beta). This causes ineffective erythropoesis and severe microcytic hypochromic anemia. An alpha chain that has no partner will form a substance that will damage the red blood cell membrane, this premature damage leads to intramedular death and ineffective erythropoesis Thalassemia intermedia Thalassemia intermedia occurs due to abnormalities in 2 chromosomes that descend from the father and mother. In thalassemia intermedia, there are 2 mutant genes that decrease, namely a combination of heavy and mild mutants, or mild mutants and mild mutants. Intermedia patients are not routine in fulfilling their blood transfusions, sometimes only once every 3 months17, once every 6 months or even once a year. However, in certain circumstances, the intermedia state can fall into a major state if the body produces a large amount of blood, or the body requires a high metabolism or other clinical conditions that weaken the physiological system of hematology or the blood system. Thalassemia minor/trait/carrier trait: Thalassemia minor (thalassemia trait) is a carrier of thalassemia, inherited from one parent so that it is heterozygous. Clinically it can be asymptomatic or accompanied by mild microcytic anemia that does not require a blood transfusion. This condition occurs in healthy people, but can pass on the thalassemia gene in their offspring. (Andriyani, 2021)

Physiological Anatomy Definition of Hemoglobin Hemoglobin is the transport of oxygen and carbon dioxide and is an iron-containing pigment found in red blood cells and functions mainly in the transport of oxygen from the lungs to all tissue cells of the body. (Muttaqin, 2012) Function of Hemoglobin The main function of hemoglobin for the human body is as a carrier of oxygen to be circulated throughout the body tissues from the lungs and in the blood circulation. The level of hemoglobin with oxygen is called HbO2 (Oxyhemoglobin). In addition to its role in transporting oxygen, hemoglobin also functions to transport carbon dioxide and carbon monoxide forms carbon monoxide bonds and forms HbCO bonds (hemoglobin carbon monoxide) bonds. Hemoglobin also affects blood pH (HASANAN, 2018) Hemoglobin binding process During the maturation phase, hemoglobin is formed in the spinal cord. Red blood cells enter the bloodstream as reticulocytes from the bone marrow. After 24-48 hours of maturation, a small amount of hemoglobin is still formed. After that, the reticucytes break down and produce mature red blood cells. Red blood cells become more fragile and stiff as they age, and eventually red blood cells break down. Most phagocytosis of hemoglobin occurs in the spleen, bone marrow, and liver, and is then reduced to heme and globin, where globin returns to the source of amino acids. Iron is released by heme and most of the 9 is transported with transfiren plasma to the bone marrow to function for the formation of new red blood cells (HASANAN, 2018).

Pathophysiology of thalassemia In the first trimester of intrauterine life, zeta, epsilon, alpha, and gamma chains are at significant levels and in some conditions form Hb Gower I, Hb Gower II, Hb Portland, and hemoglobin F. Hb Gower and Hb Portland soon disappear, HbF will settle and form respiration pigments during intrauterine life. Before birth, the production of gamma chain (γ) begins to decrease so that after 6 months of age after birth, only a small amount of HbF (<2%) is left detected in the blood. In the early phase of intrauterine life, beta chain synthesis is maintained at low levels, but gradually increases to significant levels by the end of the third trimester and continues into neonatal and adulthood. Delta chain synthesis remains maintained at low levels until adulthood (<3%). Therefore during normal development, fetal and Portland Gower Hb synthesis is replaced by HbF synthesis, and later replaced by adult hemoglobin, HbA and HbA2. The γ chain that is replaced by the β chain will bind to the α chain to form HbA. The reduction of β globin chains leads to a decrease in the synthesis of HbA and an increase in α free globin chains, leading to the formation of hypochromic and microcytic erythrocytes. An imbalance in the synthesis of globin chains α and β affects the degree of thalassaemia. Precipitates formed from the accumulation of α chains form an inclusion body in erythrocytes, causing erythrocyte membrane damage as well as premature destruction of developing erythroblasts in the bone marrow.

Membrane damage causes immunoglobulins and complements to bind to the membrane, signaling macrophages to get rid of damaged erythroid precursors and erythrocytes. Reticuloendothelial cells remove abnormal erythrocytes from the spleen, liver, and bone marrow before their lifetime ends, creating a state of hemolytic anemia. Ineffective erythropoiesis as well as hemolysis are the main signs of thalassemia β . Erythrocytes can still maintain the production of γ chains, binding to excess free α chains to form HbF. Such binding causes levels of free α chains to decrease, thereby reducing disease symptoms and providing additional hemoglobin capable of binding oxygen. However, the increase in HbF levels results in an increase in oxygen affinity resulting in hypoxia. The state of anemia and hypoxia stimulates the production of erythropoietin. Ineffective erythropoiesis increases, causing bone enlargement and deformity. Ineffective erythropoiesis inhibits the production of hepcidin by the liver, which is responsible for inhibiting iron absorption and iron release from macrophages and hepatocytes. Thus, in thalassemia beta there is an increase in iron absorption and iron release from macrophages, resulting in iron accumulation in the circulation and then in the organs. Iron is stored in the tissue in the form of ferritin, which is then degraded to hemosiderin, so in thalassemia beta the levels of ferritin and hemosiderin increase. (Andriyani, 2021).

Governance According to (Lestari, 2024) The management of thalassemia patients to date is in the form of supportive therapy. The supportive therapy provided is adjusted to the main pathology, namely the treatment of anemia. In general, the management carried out for thalassemia patients is Giving blood transfusions The administration of blood transfusions in thalassemia patients depends on two things: body weight and initial HB. The determination of the number of transfuses is as follows: Body weight (BB) X (12-Hb early) X 4= amount of blood needed (one term). Transfusion administration with Hbawal above 9 Transfusions is done in 1 term. If Hb 7-9 transfusions are divided in 2 terms, if Hb 5-7 transfusions are divided in 3 terms. While Hb is under 5 transfusions under supervision by doctors and nurses. Giving iron cleats Desferal or called iron chelation is a treatment action that is carried out after a blood transfusion. In the action of administering iron chelation with thalassemia patients, it aims to maintain the stability of Fe (iron) in the body. Nutritional Supplementation Thalassaemia patients experience various metabolic conditions due to anemia disorders and can result in growth and developmental disorders. The nutrition of thalassaemia patients must be considered considering the condition of iron overload due to transfusion. The administration of antioxidant nutrition is indicated for all patients such as intake containing calcium, vitamin D, folate, trace minerals (copper/copper, zinc, and selenium), and antioxidants (vitamins C and E).

Splenectomy or removal of the spleen A splenectomy is an incisive procedure to cut off the splen or spleen from the body. Surgical splenectomy will be an alternative when routine transfusions can be performed from an early age and take place adequately. Splenectomy may be indicated for circumstances such as increased transfusion needs of more than 200 – 250 ml PRC/kg/year or 1.5 times the usual need, leukopenia and thrombocytopenia. Vaccination Intensive and optimal treatment in thalassaemia patients involves vaccination measures to prevent several diseases. The pneumococcal vaccine is recommended from 2 months of age, and repeated at 24 months of age. Re-giving can be given every 5 to 10 years. Routine transfusions can cause an increased risk of hepatitis b, so the hepatitis b vaccine should be given, hepatitis monitoring is carried out routinely with examinations such as SGOT, SGPT, IgG and IgM for hepatitis. The infuenza vaccine is adequately administered every year. In addition, monitoring HIV must also be considered considering that patients get donations from others.