Blood transfusion is mandatory for all children with Thalassemia major and for those children with Thalassemia intermedia who cannot maintain Hb above 7 gm% or for those who show evidence of growth retardation, severe bony changes or hypersplenism. Regular blood transfusions are presently the mainstay of treatment of Thalassemia.

In a-Thalassemia, a chain synthesis is decreased. In b-thalassemia, b chain synthesis is decreased. Excessive a chains precipitate in red cell membrane and damage it. It leads to premature red cell destruction both in the bone marrow and peripheral circulation particularly in reticuloendothelial system of spleen (ineffective erythropoiesis and hemolysis).

Synthesis of gamma chain persists after fetal life. Increased fetal hemoglobin (HbF) with its high affinity for oxygen leads to tissue hypoxia, which in turn stimulates erythropoietin secretion leading to both medullary and extramedullary erythropoiesis (expansion of bone marrow space) causing a characteristic hemolytic facies with frontoparietal and occipital bossing, malar prominence and malocclusions of teeth. Complications include distortion of ribs and vertebrae and pathological fracture of the long bones, splenomegaly and its complications (hypersplenism), hepatomegaly, gallstones and chronic leg ulcers.

Transfusion is started at the time of diagnosis, that is when the child becomes clinically symptomatic.

Thalassemia intermedia presents a complex therapeutic problem as these children may lead near normal life without being transfusion dependent. Occasionally, it may not be clear whether one is dealing with Thalassemia intermedia or major.

Majority of Thalassemia intermedia can be detected by

• Age of onset of symptoms is usually more than two year.
• Increased indirect hyperbilirubinemia of 2 mg/dl or more.
• High reticulocyte count more than 10% at the time of diagnosis.
• Hb is usually maintained above 7-10 gm% without blood transfusion.

If there is a doubt about the diagnosis, it is wiser to follow up these children regularly and transfusion therapy should be started only if Hb drops to less than 6-7 gm% and then regular transfusions are continued to maintain Hb level above 10-12 gm%.

Transfuse them with triple saline washed packed cells to avoid transfusion reactions as saline washing minimises reactions due to leucocytes and plasma proteins.

Frozen cells: Freezing the RBCs to -80 degree Celsius, with an addition of glycerol to protect RBCs from damage of freezing and thawing, preserves 2,3-DPG and ATP in the red cells. Thus frozen cells can be stored as long as seven years at -20 degree Celsius. However, cost and high technology is involved, which do not permit its use even in developed countries.

Leucocyte filters are also effective in eliminating neutrophils. Various filters available are ImmuGuard 500, Sepsea, Travanol, Ery Pure B, Pal leucocytes filters, which cost around Rs.150-500, and are not reusable. They are superfluous for those patients who have not developed febrile reactions.

Transfusion regimen may be (1) low transfusion regimen where Hb is maintained around 6-10 gm%, (2)hypertransfusion: Hb level 10-12 gm% and supertransfusion where Hb is maintained at 12-14 gm%.

The popular transfusion regimen of today is a hypertransfusion regime which aims at maintaining mean hemoglobin levels at12.5 gm/dl and pre-transfusion level not less than 10 gm%.

Such a regimen permits normal growth and physical activity, suppresses erythropoiesis, thus preventing skeletal changes and gastrointestinal iron absorption and also inhibits extra-medullary hemopoiesis, thereby preventing splenomegaly and hypersplenism.

With this regime, requirement of blood is high only at the start of therapy, and does not produce more iron overload than the low transfusion regime.

Pre-transfusion Hb level should be high enough to inhibit bone marrow activity i.e. around 9.5-10 gm%.

Post-transfusion Hb should not go above 16 gm/dl, since it can lead to hyperviscosity and its complications.

When this therapy is started late in life when already hypersplenism has set in, splenectomy becomes mandatory.