Thalassemia: Everything You Want To Know About This Blood Disorder

When planning to have a child, the couples are recommended to get screened for beta thalassemia. This blood disorder poses several risk factors on pregnancy, including heart problems, hypothyroidism, gestational diabetes, and a higher probability of infections among others.

But then what is Thalassemia? What are the symptoms? What are the tests needed for diagnosis? How to manage it?

This post addresses every question you have – everything you want to know about thalassemia.

What is Thalassemia?

Thalassemia is an inherited blood disorder in which the amount of hemoglobin in your blood is inadequate or in abnormal amount. Hemoglobin is the protein in the RBC or Red Blood Cell that helps carry oxygen. Lack of it results in destruction of large number of RBC. This leads to anemia, a condition in which the blood doesn’t have enough healthy red blood cells; it requires regular blood transfusions for treatment.

There are two forms of serious thalassemia. (i) Alpha-thalassemia; one or more of alpha globin genes have an abnormality. (ii) Beta thalassemia; one or more beta globin genes have an abnormality.

Symptoms of Thalassemia

The symptoms of thalassemia aren’t visible. However, there are a few common signs that do help in diagnosis. Some of them include:

  • Shortness of breath
  • Chest pain
  • Yellow or Pale skin
  • Delay in growth and development
  • Fatigue and drowsiness
  • Headaches
  • Dizziness
  • Higher heartbeat
  • Leg cramps
  • Lack of appetite
  • Dark urine
  • Bone deformities

This isn’t an exhaustive list of thalassemia symptoms. Moreover, even when these symptoms are present, physical examination isn’t enough to diagnose thalassemia; at times, the problem could be different. The necessary tests need to be done to make the conclusion.

Causes of Thalassemia

The symptoms of thalassemia vary between individuals. Their severity depends on the type of thalassemia or what causes the disorder.

As mentioned previously, thalassemia is an inherited blood disorder, passed through genes from the parents to children. If one of the parents is “carrier” or affected by the disorder, the child may develop thalassemia minor; symptoms would be either absent or very mild. However, if both the parents are carriers, the child has a higher risk of inheriting a serious form of disease.

Our normal hemoglobin, called hemoglobin A, has 4 protein chains: Two alpha-globin and two beta-globin, both of which control globin-chain production. Due to spontaneous mutation, across the population, hemoglobin genes are present at low prevalence; they are often harmless. They fall into two groups: (i) Structural variants - it changes the amino acid sequence and produces unusual hemoglobin (ii) Thalassemias - it lowers the production of globin chains. When a person inherits a combination of hemoglobins, the chances of having serious hemoglobin disorder rises.

So, in the end, whether a person has alpha thalassemia or beta thalassemia depends entirely on how many faulty genes they have inherited.

Types of Thalassemia Syndrome

There are three types of thalassemia syndrome:

1. Thalassemia Minor: People with this carrier state live a normal life. In fact, it isn’t even referred to as a disease or disorder. These people have little to no symptoms; they only have mild anemia.

2. Thalassemia Intermedia: A stage advanced from minor thalassemia, people with this carrier state does not have serious anemia. However, they do have a higher risk of iron overload and various other complications. On occasions, they may need a transfusion and be put on medication.

3. Thalassemia Major: People with this carrier state have severe anemia. They are the most affected with very low hemoglobin, which results in severe symptoms. To survive, they require transfusion regularly or bone marrow transplantation.

Diagnosing Thalassemia

To diagnose thalassemia, your doctor would ask you to do several tests such as following :-

1. Complete Blood Count: CBC helps determine the levels of hemoglobin in the blood, as well as the level and size of red blood cells. The normal range of Hgb for women is between 12.3 and 15.3 gm/dL; for men, it’s between 14 and 17.5 gm/dL. In infants, the normal range is 9.5 to 13 gm/dL.

2. Reticulocyte Count: This checks how fast red blood cells called reticulocyte are produced and released into the bloodstream by the bone marrow. Reticulocyte count rises when red blood cells are destroyed in large numbers and prematurely. A normal range of reticulocytes in the blood in adults is between 0.5 and 2.5 percent; in infants, it’s between 2 and 6 percent. A higher percentage is a sign of anemia.

3. Genetic Testing: This includes DNA analysis. It identifies the changes in chromosomes, genes or proteins, which helps determine whether or not the person has faulty genes or thalassemia.

4. Prenatal Testing: This test is done to find if the fetus has thalassemia and its severity. It includes Chronic Villus Sampling (CVS) and Amniocentesis. Chronic Villus Sampling is done around the 11th week of pregnancy by testing a piece of placenta. Amniocentesis is done around the 16th week by testing the fluid around the fetus, also called amniotic fluid.

In addition, the doctor might also do a physical examination. For instance, an enlarged spleen can help them establish that the patient might have hemoglobin H disease.

Suggestive Findings

If any of the mother or father – or both – is a carrier, β-thalassemia should be suspected in an infant or a child younger than 2 years. Clinical and newborn screening findings should be done. Clinical findings include mild jaundice, severe microcytic anemia and hepatosplenomegaly. Newborn screening, resulting in the positive or suggestive screen, is done through isoelectric focusing, capillary electrophoresis, or high-performance liquid chromatography on newborn blood spots. The findings will reveal microcytic anemia, amount of HbA and HbF after the age of 12 months, and the clinical severity of anemia. Further, for at-risk newborn under 12 months with positive/suggestive screening or unexplained microcytic hypochromic anemia, identification of biallelic pathogenic variants in HBB on molecular testing can be useful for diagnosis.

For individuals who are in their midlife or beyond with similar but milder clinical findings, might be suspected of thalassemia intermedia. The right course of action should be followed after conclusive diagnosis, based on the severity of the condition, which could include occasional transfusion. For individuals who have thalassemia minor, they are usually asymptomatic with only mild anemia; they can live a normal and healthy life.

Establishing the Diagnosis

The diagnosis of beta-thalassemia, in proband younger than 12 months, is based on several findings. It includes: (i) Positive or suggestive newborn screening result; (ii) Microcytic hypochromatic anemia with anisopoikilocytosis and nucleated red blood cells on peripheral blood smear; (iii) Biallelic pathogenic variants in HBB identified on molecular genetic testing.

The diagnosis of beta-thalassemia, in proband older than 12 months, is based on several findings. It includes:

(i) Microcytic hypochromic anemia;

(ii) Anisopoikilocytosis with nucleated red blood cells on peripheral blood smear;

(iii) Haemoglobin analysis that reveals a complete absence or decreased amounts.

Each of these findings has its reference point that doctors use to make the final diagnosis and outline treatment plan.

Managing Thalassemia

Thalassemia is a serious blood disorder that can lead to many life-threatening conditions. Its treatment varies, based on several factors, including the severity of the disease. Some of the prevalent treatments include:

  • Medications
  • Blood transfusions
  • Bone marrow transplant
  • Surgeries to remove gallbladder or spleen.

For patients with thalassemia intermedia, the medical professional would usually recommend symptomatic therapy sporadic red cell transfusions, folic acid supplementation, and iron chelation. For those with thalassemia major, a host of curative measures will be deployed. Regular transfusions will aim to correct anemia, suppress erythropoiesis, and inhibit increased gastrointestinal absorption of iron. As an alternative to chelation therapy and transfusion, bone marrow transplantation from an HLA-identical sibling can be recommended too. In addition, in recent times, owing to its high probability of success and low risk of GVHD or Graft-versus-Host Disease, cord blood transplantation has become a popular option now.

Treating thalassemia also includes managing secondary complications efficiently. It includes regularly assessing iron overload through liver biopsy, ferritin concentration, biosusceptometry, more; iron overload should be treated through rigorous chelation therapy. In addition, myocardial siderosis should be assessed regularly, cardiac function be monitored, and osteoporosis should be treated.

Furthermore, the medical professionals would keep a close eye on the patient to see the effectiveness of transfusion therapy, determination of serum ferritin concentration, and evaluation of growth and development during childhood. They would also conduct an overall assessment of eyes, heart, endocrine function, and more. Also, if a family member is identified with the pathogenic variants, molecular genetic testing would be offered for early diagnosis and treatment.

Genetic Counselling

A sibling of a person with thalassemia has a 25 percent chance of being affected, 50 percent chance of being a carrier with no symptoms, and 25 percent changing of not being a carrier. That’s because beta thalassemia is inherited in an autosomal recessive manner. Once the couple is diagnosed with HBB pathogenic variants, they would have to go through genetic counselling wherein the professional would provide them with insights and advice on the risks of thalassemia in the future child. The couple would be given an effective plan, which could include Preimplantation Genetic Diagnosis (PGD) and prenatal testing among other measures, to minimize the risks during pregnancy.


As per the estimates, people with the most severe form of beta-thalassemia die by the age of 30. (Source) Diagnosing the disorder at the earliest and taking proper measures as soon as possible is essential here. Generally, those with minor thalassemia live a normal life. Those with a severe form of thalassemia encounter several challenges, including heart failure and endocrine issues. Also, since it affects the reproductive organ development which can cause several fertility difficulties, women should work closely with a medical team to ensure their good health, as well as that of the future baby.

Talk to your doctor and follow their treatment plan to improve the quality and longevity of your life. It’s possible to live a good life with thalassemia. In the end, it comes down to your mindset and how committed you are in the treatment/management.

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Dr. Dipanjana Datta

Dr. Dipanjana Datta is a Genetic Counselor and has 13 years of experience in the field of human genetics. She is also the State(WB) Coordinator for the Organization of Rare Disease India. Dr. Datta was a post doctoral fellow from Virginia Common Wealth University (VCU) and has published in numerous international journals of repute like PNAS, Journal of Neurology, Plos One, International Journal of Gastroenterology, etc. She is the member of various esteemed genetic associations like American Society for human genetics (ASHG), Indian Society for human genetics (ISHG), Calcutta consortium of human genetics (CCHuGe), and Society for Biological Chemist (SBC) and the Indian Immunological Society (IIS). She is also is a member with Indian genome variation Consortium.

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