Thalassemia is a disease of the blood in which there is increased destruction (hemolysis) of the red cells. There are various severities of the disease from thalassemia major-the severe form in which the patient needs regular blood transfusions in order to survive, to thalassemia minor an asymptomatic carrier state with patients of thalassemia intermedia in between. This is an inherited (can be passed on to the children from parents) blood disorder, in which the inheritance is autosomal recessive, that is both parents must carry the defective gene in order to pass on thalassemia major to the child.
Historically it is believed that the defective gene originated from near the Mediterranean region, hence the name thalas meaning sea. It is found in many countries of Europe, and Asia, including India.
What is Thalassemia?
In Thalassemias there is anemia- that is the hemoglobin in the blood is less than the normal level, this is due to the rapid breakdown of the red cells, a process called hemolysis. The patients of thalassemia major have severe anemia, which needs regular blood transfusions for treatment.
Cause of Thalassemia
The anemia is due to increased destruction of the red cells, this increased destruction is due to a genetic defect that decreases the red cell survival.
Thalassemias are inherited disorders—that is, they are passed from parents to children through genes. People who inherit the defective hemoglobin genes from one parent but normal genes from the other are called carriers. Carriers often have no signs of illness other than mild anemia, but carry the defective gene. Normal hemoglobin, also called hemoglobin A, has four protein chains—two alpha globin and two beta globin. The two major types of thalassemia, alpha and beta, are named after genetic defects in these protein chains. This can affect both males and females.
Types of Thalassemia Syndrome
The carrier state is called thalassemia trait or thalassemia minor, these patients have very few problems and lead a normal life. The thalassemia intermedia patients can be like either thalassemia major, or minor or somewhere in between. Usually they do not have such severe anemia as thalassemia major patients, though many need transfusion. They are at risk for iron overload and need medicines to treat this, even those patients who do not get extra blood transfusions may also develop iron overload. Patients of thalassemia major are the most severely affected.
Thalassemia Trait / Minor
Normal, with only mild anemia
Occasional blood transfusion to regular transfusions, may benefit from medicines. They have a risk of iron overload and other complications
Severe anemia needing regular transfusions in order to survive or a bone marrow transplant. Risk of iron overload and other complications
Thalassemia minor/trait is not a disease and may have only mild anemia and will not be discussed further. Patients of thalassemia major have the signs of anemia, as the hemoglobin becomes lower they have more problems. The symptoms of anemia include- tiredness, fatigue, pallor, breathlessness, difficulty breathing high heart rate and if severe enough even heart failure. This is due to lack of oxygen in the blood. The severity of symptoms depends on the severity of the disorder and the hemoglobin level.
How do Patients of Thalassemia present?
Patients with beta thalassemia intermedia have mild to moderate anemia. They also may have other problems, such as:
Patients with beta thalassemia major have severe anemia. The signs and symptoms of disease usually occur within the first 2 years of life. They may include severe anemia and other health problems, such as:
How to Diagnose Thalassemia?
Special blood tests are need to diagnose thalassemia, a routine blood test can only tell the degree of anemia, but red cell indices like MCV are usually low and a peripheral smear findings may make your doctor suspect thalassemia.
The special tests to confirm thalassemias detect the abnormal hemoglobin chains in the blood, for beta thalasemia and some other hemoglobinopathies an HPLC (high performance liquid chromatography, this separates different hemoglobins by their physical properties) test is usually ordered, for alpha thalassemia the confirmatory test is the genetic test for presence of abnormalities in the genes.
If the baby is less than one year old these tests may be needed to be repeated after one year of age, if the patient has already received a blood transfusion then thee tests are not valid, and the doctor may have to rely on reports of the parents blood to diagnose a child of suspected thalassemia. Hence the tests done before a blood transfusion are the most reliable.
The treatment for thalassemias depend on the type and severity of the disorder. Thalassemia trait patients do not require treatment, but it is important for them to know that if they marry another thalassemia trait individual then they have a risk of bearing a child who has thalassemia major.
Treatment for thalassemia major patients includes regular blood transfusions of packed red cells to keep the hemoglobin more than 10 g/dl, care needs to be taken to prevent diseases like hepatitis B, C and HIV, through proper blood banking practices and testing of donors. The frequency of transfusion is dependent on the severity of disease, spleen size, allo- immunization and other factors. Discuss requirement and changes of frequency with your treating doctor.
The patient needs regular follow up for measurement of iron levels, when the iron levels are increased iron chelation (key-LAY-shun) therapy needs to be started. This is available in the form of several medicines which must be taken under the supervision of a qualified doctor to ensure the best iron removal as well as prevention of toxicity. Iron overload is important to treat, as the extra iron is toxic to the body and excess iron can damage the liver, heart and affects the endocrine glands leading to short stature, delayed or even absent puberty, diabetes etc. Bone problems like osteoporosis and increased risk of fractures are seen in older children with thalassemia. Folic acid supplements are recommended for all patients with hemolytic anemia, calcium and other supplements are also given to the patients, as and when they are needed and may be tailored to the needs of the patient.
Chelation medicines available in India
Blood and Marrow Stem Cell Transplant
The only known curative treatment is a bone marrow or peripheral blood stem cell transplant. This procedure replaces the defective blood forming cells with healthy blood forming cells from another person (allogeneic / allo-), usually a brother or sister who are HLA matched (genetic match suitable for transplant) and do not have the defective genes. It cannot be done from the cord blood of the patient, as this also has the same defective gene. Cord blood transplant can be done from a sibling or another person but is not usually preferred for thalassemia patients, due to risk of rejection, but can tried if no bone marrow matched donor is available. Even cord blood needs HLA matching. Sometimes a non related HLA matched transplant BMT may be performed, the results are not as good as with an HLA matched sibling, there are more risks and complications and the cost is more. However, this may be suitable for some patients without a sibling donor.
The benefit of bone marrow transplant is that after this procedure the patient will not need further blood transfusions, but in patients with iron overload they may still need iron chelation for several years to reduce their iron levels. All transplants do have risks (allo -BMT, PBSCT or cord blood), patients may develop complications during and after the procedure, the serious complications include infections, veno-occlusive disease, graft versus host disease, rejection and even death. Usually the risks are more in older children or those with enlarged liver and spleen and liver fibrosis. Patients with very high iron overload can develop heart problems even during the transplant and liver failure, hence, proper iron chelation is needed before transplant. Proper iron chelation, right from infancy will help to reduce the chances of complications.
Hydroxyurea is an oral medicine that is a fetal hemoglobin inducer, and most commonly used in thalassemia intermedia and sickle cell disease. It is Hydroxyurea is cytotoxic, anti metabolic medicine. The exact mechanisms by which it increases fetal hemoglobin (a normal hemoglobin) is not fully understood. Hydroxyurea treatment increases γ-mRNA expression leads to an improvement in the α/non-α chain imbalance and more effective red cell production, thereby increasing the hemoglobin and need for blood transfusion. Hydroxyurea should be used at a starting dose of 10 mg/kg/day, check for response every 3 months. The dose may be increased to a maximum dose of 20 mg/kg/day. If no response it may be discontinued 6 months.
Complications of Thalassemias
With better blood transfusion practices and chelation therapy even patient without bone marrow transplant are surviving longer and many lead productive lives.
The complications which may occur in older thalassemia patients include
If you or your family members have thalassemias, talk to your doctor who can help you before planning a family. This will help you understand the chances of passing on the defect to your children and help you have an unaffected child through prenatal testing.
Prenatal testing involves taking a sample of amniotic fluid or chorio villus sample (CVS) tissue tests done on the fluid or tissue can show if the baby has thalassemia.
The content of this module has been validated by Dr Tulika Seth, Department of Hematology, AIIMS, New Delhi on 24/9/2014.