Thalassemia and Related Disorders

What is Thalassemia and Types of Thalassemia?

Thalassemia is an inherited blood disorder characterised by low haemoglobin (Haemoglobin is an iron rich protein present within the Red Blood Cells of the body. Haemoglobin is responsible for carrying oxygen to all parts of the body). Normal haemoglobin binds iron with alfa and beta globin (protein) chains. Due to genetic mutations in both the genes inherited from the parents, either alfa or beta chains are absent or reduced. This results in precipitation of other globin chains inside the red blood cells, leading to deformity of the red cells. These deformed red cells get destroyed either within the bone marrow (spongy material within the bones) or spleen resulting in anemia (Pallor). This is called Thalassemia Major.

When an individual inherits only one abnormal gene, the manifestations are very mild. This is called Thalassemia Minor or Thalassemia Trait.

The commonest form of Thalassemia in India is Beta-Thalassemia, where Beta-globin chains are deficient. When instead of absolute absence of one type of globin chain, there is reduction only; the condition is called Thalassemia Intermedia

Other Thalassemia like Syndromes such as HbE, HbDetc when co-inherited with Beta-thalassemia gene give rise to Thalassemia Intermedia

What are the Symptoms of Thalassemia Major?

The symptoms appear between 3-7 years age. The child starts becoming listless, irritable and pale. The parents often visit the doctor several times before this is detected. The spleen enlarges in size and the eyes turn yellow from jaundice. The child is often in pain due to rapid expansion of bone marrow.

What are the Symptoms of Thalassemia Intermedia?

This depends on the severity of the affection of globin gene production. In more severe form, the age of onset and symptoms are similar to Thalassemia Major. In others, the patient might present in late childhood or even in adulthood with yellowish discolouration of the eye and facial changes of Thalassemia with moderate anemia.

What are the Symptoms of Thalassemia Trait?

This does not produce any symptom and is often detected on routine blood tests. The red cell morphology bears all the features of iron deficiency, although serum iron levels are high in these patients.

How do we Diagnose Thalassemia?

• Complete Blood Count: An astute haematologist easily picks up the diagnosis on routine blood tests.
• Hemoglobin Electrophoresis: This is needed to confirm the diagnosis. HbF is the major component with very little of normal haemoglobin in Thalassemia major. The ratio of normal Hb to HbF varies considerably in Thalassemia Intermedia. This test has to be undertaken before any blood transfusion has taken place. If the patient is transfused, the results can be false negative.In Thalassemia Trait, only HbA2 is raised.
• Genetic Tests
  Genetic tests are done to test for the mutations of Thalassemia. This is needed in the following situations:
  • When the child is already transfused and the diagnosis cannot be confirmed by electrophoresis.
  • When a couple wants to confirm the status of the foetus i.e. antenatal testing.

How do we treat Thalassemia Major?

There are two approaches to the treatment of Thalassemia major:

Transfusion and Chelation (Removal of iron from body)

• This involves regular red cell transfusion to maintain the Hb above 12 gm% and not let it drop below 9 gm%.
• However, such regular transfusion, loads our body with excess iron which affects the heart, liver and other organs resulting in complete failure of these organs within a decade, if left untreated.
• There are medicines, both Intravenous and Oral to remove excess iron from our body.
• Effective iron chelation helps in maintaining organ function in regularly transfused patients.
• Other side effects of transfusion include :-
  • Transmission of viral infections
  • Transfusion reactions
  • Development of antibodies against red cells.
• During chelation, the effect on eyes and ears has to be monitored. Odd infections with bacteria like Yersisnia can happen.

Bone Marrow Transplantation (BMT)

• ALLOGENEIC Bone Marrow Transplantation (BMT) is the only curative treatment for this condition. This works by replacement of diseased stem cells by healthy ones.
• This doesn’t change the genetic composition of the patient, it only changes the genetic composition of blood stem cells resulting in production of normal red cells.

What is the best age for patients with Thalassemia to undergo Bone Marrow Transplantation?

• Best age is between 2 to 5 years.
• However, successful BMT has been carried out in older children and young adults.

Who can be the donor?

• Matched Family donor is the best option.
• A person who has Thalassemia trait can be a donor for a patient with Thalassemia major.
• Results with Matched Unrelated Donor are improving.
• Recent studies have shown that HAPLOIDENTICAL (Half Matched) FAMILY DONOR might be a viable option for these patients.

How do we predict the success or failure of BMT in a particular patient?

a. Prof. Lucarelli from Pessaro, Italy had proposed a scoring system for patients undergoing BMT for Thalassemia.

• This takes into account the effectiveness of transfusion, chelation and degree of iron overload
• The patients are classified as Class I, Class II, Class III.

b. Outcome based on Pessaro Classification: Thalassemia free Survival

• Class 1- 90%
• Class II- 80%
• Class III- 60%

Do patients with Thalassemia Intermedia need BMT?

Following categories of patients need Bone Marrow Transplantation

• Those with severe symptoms
• Those who are transfusion dependent
• Those who choose to be cured knowing the risks and benefits