Thalassemia- Is There a Potential Cure?

Thalassemia- Is There a Potential Cure?

Thalassemia- Is there a potential cure

Thalassemia is one of the most common genetic diseases worldwide. It is estimated that around 60,000 individuals are born it with every year.

What Is Thalassemia?

They are a group of autosomal recessive inherited conditions where there is decreased or absence of synthesis of one of the two polypeptide chains (α or β) that form the normal adult human hemoglobin molecule (hemoglobin A, α2/β2), which results in reduced hemoglobin in red cells leading to anemia.

Thalassemia = thalassa (sea) and haima (blood)

Thalassemia Syndromes are named according to the globin chain affected.

β globin gene defects may give rise to β thalassemia, and α globin gene defect may cause α thalassemia.

How Can Thalassemia be Diagnosed?

The Symptoms of hemolytic anemia appear first which includes paleness, hepatosplenomegaly- directly from birth in α thalassemia. While in β thalassemia these symptoms appear after many months of birth with the disease.

Investigatory Workup

1. Laboratory investigations reveal classically microcytic, hypochromic red blood cells (mean corpuscular volume <70 fL), not responding to iron supplementation.

2. Second-line testing consists of separation and measurement of the hemoglobin fractions with high-performance liquid chromatography (HPLC) or capillary electrophoresis.

3. Third-line testing at the DNA level by standard Gap-PCR technologies or direct DNA sequencing.

Can Thalassemia be Prevented?

Prevention of thalassemia is based on public awareness of the disease, detection of carriers, genetic counseling, and prenatal testing.

Carriers of α thalassemia should be offered to counsel to estimate the risk of hydropsfetalis.

Testing and counseling should also be offered to all first-degree relatives of a patient diagnosed with thalassemia.


Asymptomatic carriers

Carriers require no specific treatment. However, they should be evaluated for iron deficiency, and Iron supplementation should be given only after confirmation of iron deficiency


Patients with thalassemia intermedia or hemoglobin H disease are monitored for progression of complications that can result from chronic hemolytic anemia.

Symptoms usually develop when the hemoglobin level is sustained at below 7.0g/dL.

A blood transfusion may be required during periods of rapid growth, infection-associated aplastic crisis, and pregnancy.

Indications for regular transfusion include growth impairment and skeletal deformities. Ifhypersplenism develops, splenectomy is indicated.

Thalassemia Major

This is the most severe form of the disease and requires intensive management with regular blood transfusions to maintain a hemoglobin level> 9.5 mg/dL

Due to regular blood transfusions, these patients develop iron overload, so iron chelation is required regularly.

Excessive Blood Transfusion- Is it a Problem?

Hypertransfusion decreases autogenous, ineffective erythropoiesis and hemolytic anemia but the patient has to face the consequences of iron overload because each unit of red blood cells adds 200 mg of iron, which can only be slowly removed from the body. The complications of iron overload are cardiomyopathy and liver cirrhosis and effects on endocrine organs causing growth impairment, delayed or absent puberty, infertility, and diabetes mellitus.

The risk of transmission of HIV, hepatitis B, and hepatitis C is always there.

How Should Iron Overload be Prevented and Treated?

Experts recommend that iron overload be treated when serum ferritin levels exceed 1000 μg/L, which will occur after 10 to20 red cell transfusions.

Oral or parenteral chelation therapy remains the mainstay to prevent iron overload.

Alternative Therapeutic Options

Splenectomy can be considered if hypersplenism causes a marked increase in transfusion requirements. In general, it should be delayed for as long as possible, in order to prevent life-threatening infections, pulmonary hypertension, and thrombi-embolic complications.

Hydroxyurea, a cytotoxic drug has also shown some benefits.

Is There a Potential Cure? The Most Common Question That Comes to Our Mind.

The only potential cure for β thalassemia is hematopoietic stem cell transplantation.

The success of stem cell transplantation depends on the number of erythrocyte transfusions received and the severity of iron overload.

The potential for success is furthermore determined by HLA matching between the donor stem cells and patient HLA. The preferred source of donor stem cells is an HLA identical family member.

Hematopoietic stem cell transplantation has shown in studies overall survival of 90% and disease-free survival of 86% for a mean follow-up period of 15 years.

The younger the patient is at the time of stem cell transplantation is the better the outcome.

Reviewed By:

Dr. Kaushal M. Bhavsar (MBBS, MD)

Assistant Professor in Pulmonary Medicine, GMERS Medical College, Ahmedabad