Diagnosis and management of thalassemia

Thalassemia is a type of hemolytic anemia in which a structural abnormality of hemoglobin renders the red blood cells susceptible to get damaged easily leading to shortened life span and hence anemia.

Lysis means breakdown and hemolytic anemia is a condition in which there is abnormally high destruction of the red blood cells.

Depending on the chain affected there are two types of thalassemia-alpha thalassemia in which the synthesis of alpha chain is decreased and beta thalassemia in which the synthesis of beta chain is decreased.

Alpha thalassemia:

There are four genes controlling the synthesis of alpha chains. Depending on the number of genes affected the disease varies in seventy from asymptomatic carrier state to intra uterine death. The genes are located on chromosome16.

Those with deletion of 1 or 2 genes may not have any symptoms. Those with deletion of 2 genes may have slightly decreased hemoglobin but may be able to lead normal lives.

Those with deletion of 3 genes suffer from mild to moderate anemia with enlargement of liver and spleen. The reticulocyte (reticulocytes are precursors of mature red blood cells) count is increased. Bony abnormalities may be present because the bone marrow expands in order to compensate for increased destruction of RBCs. Hemoglobin electrophoresis in the newborn period shows increase in a type of hemoglobin called Bart’s hemoglobin which is made up of four gamma chains. Later hemoglobin H (made up of 4 beta globin chains) will be present.

Deletion of all four genes leads to severe anemia in the fetus itself. It results in either intra uterine death or early neonatal death.

Mild alpha thalassemia must be distinguished from beta thalassemia and iron deficiency anemia. As iron deficiency anemia is more common than thalassemia especially in developing countries iron may be prescribed for this condition unnecessarily and it can even be harmful.

Serum iron and ferritin will be normal or even increased in thalassemia where as both will be decreased in iron deficiency anemia. Electrophoresis helps in distinguishing between alpha and beta thalassemia.

Treatment: Those with mild disease may not need any treatment. Those with moderate disease should receive folic acid supplements as its requirement is increased. Transfusion may be required if anemia is significant. Removal of spleen may be necessary if it is causing problems.

Beta thalassemia

There are only 2 genes for beta chain synthesis one or each chromosome 11. Persons with beta thalassemia may be either heterozygous (only one gene is affected) or homozygous (where both genes are affected ). Heterozygous people have what a called thalassemia minor which may not require any treatment.

But if there is family history of thalassemia it is important to screen all the children to identity those with thalassemia minor so that marriage between 2 people with this condition can be avoided.

Those with thalassemia major will be normal at birth but quickly develop anemia during the first year itself.

Without proper management they suffer from growth retardation massive enlargement of liver and spleen and changes in bones manifesting as prominent forehead and large maxilla (cheek bone) due to expansion of bone marrow. Pathological fractures can occur.

Laboratory examination reveals low hemoglobin and increased reticulocyte count. Hemoglobin electrophoresis will help in diagnosis after 6 month of age. Instead of normal adult hemoglobin fetal hemoglobin will be present. As in the case of alpha thalassemia the condition has to be differentiated from iron deficiency anemia.

Without treatment most of the children die during the first decade of life.

Treatment: There are 2 options for treating thalassemia. One is regular transfusion to maintain hemoglobin level between 9-10 grams per deciliter. A serious complication of repeated blood transfusion is accumulation of excess iron in the body. Human body is not equipped to eliminate excess iron which can get deposited in heart, liver and other tissues.

Such patients will die of heart failure or other complications. Hence they need to be given a drug which chelates iron and removes it from body. Currently deferoxamine is the drug available for this. Unfortunately this has to be given as an injection and hence patient compliance will be poor. It is also costly. Research is going on to bring out orally effective chelating agents.

Some children may need splenectomy (removal of spleen). They are at risk of developing serious pneumococcal infections and hence should receive pneumococcal vaccine.

The other option is bone marrow transplantation. This requires a compatible donor. The procedure is costly. One person’s body will not accept cells from every other person. It will mount an immune response against transplanted cells and destroy them. Hence several tests have to be done to ensure compatibility between two individuals.

Return to common childhood problems from thalassemia