Thalassemia

"Thalassemia is just like an anaconda in a swamp. You don't realize it's there until it squeezes the life out of you."

What is Thalassemia

Thalassemia is an inherited blood disorder characterized by reduced or absent production of hemoglobin. Hemoglobin is the protein molecule in red blood cells that carries oxygen throughout the body. When there isn't enough hemoglobin, the body's organs don't get enough oxygen and are unable to function properly.

Understanding Hemoglobin

Hemoglobin is made up of two types of protein chains: alpha and beta. Thalassemia occurs when there is a defect in one of these genes, leading to reduced production of either alpha or beta chains. This results in abnormal red blood cells that are quickly destroyed, leading to anemia.

Role of Bone Marrow

Bone marrow is the soft, spongy tissue inside bones that produces blood cells. In people with thalassemia, the bone marrow tries to compensate for the lack of healthy red blood cells by producing more, which can lead to bone expansion and abnormalities, particularly in the face and skull.

Alpha Thalassemia

Alpha thalassemia occurs when one or more of the four alpha-globin genes are missing or mutated. The severity of the condition depends on how many genes are affected:

One Gene Mutated (Silent Carrier)

The person is a silent carrier with no signs or symptoms. They can pass the mutated gene to their children, but typically lead normal, healthy lives without any health complications from thalassemia.

Two Genes Mutated (Alpha Thalassemia Trait)

The person may have mild anemia, often mistaken for iron-deficiency anemia. They might experience mild fatigue but can generally lead a normal life. This is also called alpha thalassemia minor.

Three Genes Mutated (Hemoglobin H Disease)

This results in moderate to severe anemia. People with this condition may need regular blood transfusions, especially during illness or stress. They may experience fatigue, weakness, and an enlarged spleen.

Four Genes Mutated (Alpha Thalassemia Major)

This is the most severe form, also known as hydrops fetalis. It is usually fatal before or shortly after birth. Affected babies are either stillborn or die shortly after birth. Some may survive with intensive medical intervention including in-utero transfusions.

Beta Thalassemia

Beta thalassemia is particularly common in people of Mediterranean, Middle Eastern, Asian, and African descent. It occurs when there is a mutation in one or both of the two beta-globin genes.

Beta Thalassemia Minor (Trait)

One beta gene is mutated. People with beta thalassemia minor have mild anemia and may not require treatment. They often don't realize they have the condition unless discovered through blood tests.

Beta Thalassemia Intermedia

Both genes are affected, but some beta-globin is still produced. Symptoms are moderate and vary widely. Some people may need occasional blood transfusions, especially during illness, while others may not need any treatment.

Beta Thalassemia Major (Cooley's Anemia)

Both beta genes are severely mutated, resulting in little or no beta-globin production. This is the most severe form and requires lifelong regular blood transfusions, starting in early childhood. Without treatment, it is fatal in the first few years of life.

Signs and Symptoms

Signs of Beta Thalassemia

• Jaundice - Yellowing of the skin and whites of the eyes due to breakdown of red blood cells
• Fatigue and weakness - Due to insufficient oxygen delivery to tissues
• Pale or yellowish skin - Result of anemia and jaundice
• Cold hands and feet - Poor circulation due to low red blood cell count
• Shortness of breath - Difficulty breathing, especially during physical activity
• Poor feeding in infants - Babies may be irritable and have difficulty feeding
• Delayed growth and development - Children may grow more slowly than their peers
• Facial bone deformities - Expansion of bone marrow causes forehead prominence and cheekbone enlargement
• Iron overload - From repeated transfusions or increased iron absorption
• Increased susceptibility to infections - Especially after spleen removal
• Delayed puberty - Hormonal changes may be delayed in adolescents

Signs of Alpha Thalassemia

• Fatigue and weakness
• Drowsiness and irritability
• Pale appearance
• Chest pain (in severe cases)
• Dizziness or lightheadedness
• Cold hands and feet
• Headaches
• Leg cramps

Diagnosis

Diagnosing thalassemia involves several tests to determine the type and severity:

Complete Blood Count (CBC)

This test measures the amount of hemoglobin and the number and size of red blood cells. People with thalassemia typically have low hemoglobin levels and smaller than normal red blood cells (microcytosis).

Reticulocyte Count

Measures the number of young red blood cells (reticulocytes) in the blood. This helps determine if the bone marrow is producing red blood cells at an appropriate rate.

Iron Studies

These tests help distinguish thalassemia from iron deficiency anemia, which can have similar symptoms. In thalassemia, iron levels are usually normal or elevated, while in iron deficiency they are low.

Genetic Testing

DNA analysis can identify mutations in the alpha and beta globin genes. This is particularly useful for confirming the diagnosis, determining the specific type of thalassemia, and for genetic counseling.

Prenatal Testing

For couples at risk of having a child with thalassemia, prenatal testing is available:

• Chorionic Villus Sampling (CVS) - Performed around 11-14 weeks of pregnancy by removing a small piece of placenta for testing
• Amniocentesis - Performed around 15-20 weeks of pregnancy by taking a sample of amniotic fluid for genetic analysis

Treatment

Blood Transfusions

Regular blood transfusions are the mainstay of treatment for severe thalassemia. They provide healthy red blood cells and maintain hemoglobin at a level that allows normal growth and activity. People with thalassemia major typically need transfusions every 2-4 weeks.

Iron Chelation Therapy

Because regular transfusions lead to iron buildup in the body, patients require iron chelation therapy to remove excess iron. This prevents iron from damaging organs such as the heart, liver, and endocrine glands. Chelation therapy can be given orally or through subcutaneous injection.

Bone Marrow Transplant

Also known as stem cell transplant, this is currently the only potential cure for thalassemia. It involves replacing the patient's bone marrow with healthy bone marrow from a compatible donor, usually a sibling. The procedure carries significant risks but can be curative if successful.

Surgery

In some cases, surgical removal of the spleen (splenectomy) may be necessary if the spleen becomes enlarged and destroys too many blood cells. However, this increases the risk of infections, so patients need vaccinations and may require lifelong antibiotics.

Folic Acid Supplements

Folic acid helps the body produce red blood cells and is often recommended for people with thalassemia to support red blood cell production.

Complications

Iron Overload

This is one of the most serious complications of thalassemia treatment. Excess iron from repeated transfusions can accumulate in the heart, liver, and endocrine glands, causing:

• Heart problems including heart failure and arrhythmias
• Liver disease including cirrhosis and liver cancer
• Diabetes due to damage to the pancreas
• Thyroid and other hormone problems

Enlarged Spleen

The spleen filters old and abnormal red blood cells from the blood. In thalassemia, the spleen works overtime to remove the numerous abnormal cells, causing it to enlarge. An enlarged spleen can trap healthy blood cells and platelets, making anemia worse and increasing the need for transfusions.

Increased Risk of Infection

People with thalassemia have an increased risk of infection, especially if they've had their spleen removed. Common infections include those caused by encapsulated bacteria. Vaccinations and preventive antibiotics are important.

Bone Deformities

Thalassemia can cause bone marrow expansion, leading to bone abnormalities, particularly in the face and skull. This can cause:

• Prominent forehead and cheekbones
• Thinning and weakening of bones
• Increased risk of fractures
• Bone pain

Life Expectancy

Thalassemia Trait

People with thalassemia trait (minor) have a normal life expectancy and can lead completely normal lives. They typically don't require any treatment and may not even know they have the condition.

Beta Thalassemia Major

Historically, without proper treatment, children with beta thalassemia major rarely survived beyond early childhood. However, with modern treatment including regular transfusions and iron chelation therapy, life expectancy has improved dramatically.

The average life expectancy for people with beta thalassemia major who receive optimal treatment is now approximately 17 years or longer, with many patients living into their 30s, 40s, and beyond. Those who receive a successful bone marrow transplant early in life can potentially have a normal life expectancy.

Factors Affecting Life Expectancy

• Access to regular, quality medical care
• Compliance with transfusion schedules
• Adherence to iron chelation therapy
• Prevention and management of complications
• Availability of bone marrow transplant
• Overall health and other medical conditions

With advances in treatment and care, the outlook for people with thalassemia continues to improve. Early diagnosis, consistent treatment, and comprehensive medical care are key to living a longer, healthier life with thalassemia.