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What is Thalassemia?

Thalassemia refers to a group of genetic blood disorders that present similar signs and symptoms. It's the most common inherited single gene disorder worldwide.

People inherit the defective gene responsible for thalassemia from one or both parents.

The severity of the disorder depends on the number of genes affected.

Who Thalassemia Affects

People at risk for thalassemia include those with a family history of the inherited blood disorder or in an ethnic group, such as:

  • Italian
  • Greek
  • Middle East
  • African
  • Asian

Hemoglobin and Hemoglobinopathies

Thalassemia belongs to a group of several related blood diseases called hemoglobinopathies characterized by structural variations in the hemoglobin molecule.

Hemoglobin is found on every red blood cell (erythrocyte) in the blood stream. In healthy people, each hemoglobin molecule has one iron (Fe) ion on each of its four heme structures.

This vital compound performs several essential functions:

  • Binds to oxygen (O2) in the lungs
  • Carries O2 to all tissues and parts of the body
  • Releases life-sustaining O2
  • Removes carbon dioxide (CO2) waste
  • Delivers CO2 back to the lungs for exhalation

The importance of hemoglobin: In short, a person with consistently insufficient hemoglobin levels most likely cannot take in and use enough oxygen to sustain life.

Microcytic Anemia

Doctors refer to a person as anemic if he has deficient levels of hemoglobin in the blood.

The body of a person with thalassemia makes abnormal hemoglobin, causing excessive red blood cell destruction. Because of this high rate of red blood cell destruction, a condition known as microcytic anemia develops.

People with thalassemia may have mild, moderate, or severe life-threatening anemia.

Types of Thalassemia

Alpha thalassemia and beta thalassemia represent the two main types of the disorder.

The alpha or beta designation depends on which gene chain, associated with hemoglobin structural protein production, fails to function:

  • Alpha globin — Four genes help control production of this protein
  • Beta globin — Two genes help control production of this protein

Thalassemia — Genetic and Clinical Classifications

The signs and symptoms of thalassemia manifest in varying degrees, depending on the type and subtype inherited.

Alpha thalassemia (thal)

Alpha thal occurs when one or more of the genes associated with production of the alpha globin protein are defective or missing. It's more common in people of Asian, Middle Eastern, and African ancestry.

Alpha thal genetic variants

  • Loss of one gene — People with this type have no symptoms and no signs of the disease, but they are silent carriers.
  • Loss of two genes — People with this type, mild alpha thalassemia, may experience the mildest anemia, but usually look and feel healthy. Their bodies produce abnormally small red blood cells, a condition called microcytosis.
  • Loss of three genes — Hemoglobin H disease results in severe, life-threatening anemia that frequently requires blood transfusions for patient survival. Left untreated, the majority of people with this type die in childhood or as adolescents.
  • Loss of four genes — This produces a condition that cannot sustain life. The majority of people with this type die in the womb.

Beta thalassemia (thal)

Beta thal differs from alpha thal in that it rarely arises due to a complete beta globin gene deletion.

Instead, the gene has a suppressed function in varying degrees. It may produce very little beta globin protein or none at all.

Beta thal mostly affects those with Mediterranean heritage, but can sometimes affect Asians and African Americans.

Beta thal genetic variants

Severity of symptoms and impact of disorder depend on the type of beta thal an individual inherited.

  • One-gene beta thalassemia — When one normal beta globin gene and one suppressed gene produce diminished levels of beta globin in varying degrees, people have abnormally small red blood cells and mild anemia.
  • Two-gene beta thalassemia — This variant of beta thal results in severe anemia giving rise to a potentially fatal condition.

Beta thal effects

  • Thalassemia minor (also called thalassemia trait) — Refers to people whose only symptoms include small red blood cells and mild to no anemia. Often, these people don’t realize they have the trait until their blood is tested.
  • Thalassemia intermedia — People with thal intermedia do experience anemia that approaches a severe level, but many do not need blood transfusions to live. Some people, with close monitoring, may rarely, or never, need a transfusion.
  • Thalassemia major — also called Cooley’s anemia. This is the life-threatening form of beta thal in which both beta genes have suppressed function or none at all. People with this form require chronic blood transfusions throughout their lives. The transfusions may cause too much iron to build up in the system and damage vital organ systems. Iron chelation therapy removes the excess iron.

Learn More About Thalassemia

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Contact the UPMC Adult Sickle Cell Disease Program at 412-692-4724 to schedule an appointment.

Thalassemia Symptoms, Diagnosis, and Complications

People with thalassemia have had it from birth, even though it may sometimes not be apparent.

Doctors usually diagnose moderate to severe thalassemia during infancy, since the signs and symptoms typically occur within the first 24 months of life. People with milder forms of thalassemia may not discover their status until much later, during a routine blood test, indicating that they have anemia.

At the UPMC Adult Sickle Cell Disease Program, you'll find specialists with experience in diagnosing and treating thalassemia.

Signs and Symptoms of Thalassemia

The signs and symptoms vary, depending on the type and subtype of thalassemia.

Babies and children with one of the severe forms — like Cooley’s anemia (thalassemia major) or hemoglobin H disease — usually exhibit symptoms of severe anemia within the first 12 months of life. The spleen often enlarges to many times its normal size, causing intense pain and a possible rupture.

Other symptoms for moderate to severe thalassemia variants include:

  • Facial bone deformities (abnormal bone protrusions in the face and forehead)
  • Fatigue (a symptom of anemia)
  • Failure to reach growth milestones
  • Jaundice (yellow tinged skin and whites of eyes)
  • Shortness of breath
  • Heart failure (unmanaged severe thalassemia)

Those with minor forms of alpha and beta thalassemias have minimal or no symptoms, but do have microcytosis (small red blood cells). A look at a blood sample under a microscope will reveal the abnormally small blood cells.

In asymptomatic people, this usually means they have the thalassemia trait, but not the disorder itself.

Complications of Thalassemia

Common complications associated with thalassemia include mild to severe anemia or an enlarged spleen that could rupture.

Tests for Diagnosing Thalassemia

Blood tests to diagnose thalassemia type and carrier status include:

  • Complete blood count (CBC) — Measures the size, maturity, and number of the various blood cells in a specific amount of blood.
  • Free erythrocyte protoporphyrin (FEP) and ferritin — Helps doctors rule out anemia caused by iron deficiency in anemia patients.
  • Hemoglobin electrophoresis — Determines the types of hemoglobin in the blood. The procedure uses A2 and F quantitation for alpha thalassemia and A2 quantitation for beta thalassemia (Cooley’s anemia).

Prenatal diagnosis of thalassemia

Doctors use chorionic villus sampling (CVS) or amniocentesis tests to determine if a fetus has thalassemia.

Since children inherit the thalassemia gene from their parents, family genetic studies can also help diagnose the type and severity of the disease. People with family members who have thalassemia, and who want to have children, should consider gene counseling to determine their risk of passing the disease to their offspring.

Almost all people with thalassemia will need continued treatment and support throughout their lives.

Those diagnosed with:

  • Moderate to major thalassemia frequently need treatment very early in life.
  • Mild forms of thalassemia may never need treatment, or need very little.
  • The thalassemia trait (silent carriers) should consider genetic counseling when planning a family, or consult a doctor if already pregnant.

See thalassemia treatment options at UPMC's Adult Sickle Cell Disease Program.

Learn More About Thalassemia Symptoms and Tests

Visit our Health Library for more on:

Contact the UPMC Adult Sickle Cell Disease Program at 412-692-4724 to schedule an appointment.

Thalassemia Treatment

Medical technology has transformed a once-fatal genetic blood disease in to a chronic illness. Comprehensive treatment models and medical advances have made it possible for many people with thalassemia to experience full, productive lives.

The experts at UPMC's Adult Sickle Cell Disease Program in Pittsburgh, Pa., provide complete and ongoing care for adults with thalassemia.

Treatment strategies depend on the type and severity of the disease.

Blood Transfusions

Blood transfusions represent the primary treatment protocol for those with moderate to severe thalassemia.

Transfusions provide healthy red blood cells with normal hemoglobin. They also help people with thalassemia feel well, participate in normal daily activities, and live to adulthood.

  • The vast majority of people with thalassemia do not need regular transfusions at all (transfusion independent).
  • Some only need intermittent transfusions. People with alpha (hemoglobin H) or beta thalassemia intermedia may need occasional blood transfusions if anemia becomes severe and causes fatigue.
  • A small number of people require regular transfusions (transfusion dependent). Those with beta thalassemia major (Cooley’s anemia) usually require blood transfusions every two to four weeks.

Treatment for transfusion independent people

Adults who do not depend on regular or intermittent blood transfusions to manage their thalassemia usually visit their doctor two to six times a year.

At each visit, the doctor will evaluate:

  • Spleen size and activity
  • Gallbladder function
  • Orthopaedic concerns
  • Nutrition

Treatment for transfusion dependent people

Transfusion dependent individuals have additional health care needs and require a comprehensive exam once a year.

They also need to have a battery of diagnostic tests before their annual visit.

These tests may include:

  • Cardiac assessment (i.e. echocardiogram)
  • Endocrine assessment (thyroid, glucose tolerance, bone density, sex hormone levels)
  • Hepatic (liver function) panel
  • Vision health exam; nutritional screen
  • Dental health exam
  • Quantitative iron staging (liver biopsy, ferritin)

Based on the results, the health care team assesses how the patient's needs may have changed and adjusts treatment strategies.

For people with transfusion dependent thalassemia, care focuses on the most common complications:

  • Transfusion
  • Excess iron levels — Iron toxicity is the leading cause of death for people with thalassemia in the western world
  • Cardiac issues
  • Endocrine system failure
  • Hepatitis
  • Infectious disease
  • Enlarged spleen (splenomegaly)
  • Psychosocial concerns

Chelation therapy — desferal infusion

Chronic blood transfusion therapy causes excessive iron buildup.

The spleen, liver, heart, and endocrine systems act as primary storage sites for the large amounts of exogenous (from an outside source) iron received from frequent blood transfusions. The body has no way of excreting this excess iron, which can lead to organ system failure, including the heart and liver.

Doctors must monitor body iron levels to facilitate survival and wellness of the transfusion dependent individual.

Testing for excess iron

At the UPMC Adult Sickle Cell Disease Program, we test iron burden using one of two procedures:

  • Ferritin test — Measures gross iron burden or drastic iron level reduction.
  • Liver biopsy — Measures iron storage in the liver by taking a direct sample of liver tissue.

Removing excess iron

People who have excessive body iron levels must have chelation therapy to remove the excess iron.

Iron chelation therapy involves daily intravenous infusions of Desferal (deferoxamine). Desferal binds to iron in the body, which then passes out in urine and stool.

Bone Marrow and Cord Blood Transplants

Proteins called human leukocyte antigens (HLA), on the surface of every human body cell, help the immune system determine whether cells belong to foreign invaders like viruses or bacteria, or whether they belong to the individual’s body cells and tissue.

HLA typing plays a critical role when trying to find a transplant donor. Proper HLA matching helps prevent transplant rejection and graft-versus-host disease (GVHD).

Bone marrow transplant

People with Cooley’s anemia, also called beta thalassemia major, are possible candidates for bone marrow transplants. Unfortunately, most people cannot find a perfect match (HLA-identical) donor.

Siblings who share both parents provide the best chance of an appropriate match. Even then, a sibling only represents a 25 percent chance of providing the required perfect match.

Those who overcome the significant hurdle of finding an HLA-identical donor will undergo chemotherapy to remove all, or almost all, of the stem cells from the bone marrow. Doctors then replace these removed cells with the donor stem cells.

In successful transplants, donor stem cells repopulate the recipient’s bone marrow and create new, normal blood cells.

Generally, the younger the person, the better the outcome of bone marrow transplantation; though adults can undergo the therapy also, provided they meet certain criteria.

Cord blood transplant

Cord blood refers to the umbilical cord blood that remains in the umbilical cord and placenta after birth. Cord blood contains an abundance of stem cells.

Cord blood transplants offer some advantages over bone marrow transplants. The biggest advantage is that recipients show a greater tolerance for a partial match (HLA-partial) donor.

As with bone marrow transplants, siblings who share both parents represent the optimal donors.

Parents can arrange to collect and store their newborn’s stem cell-rich cord blood for potential future use.

Other Thalassemia Treatment Options

  • Daily folic acid supplements
  • Spleen removal (only when necessary)
  • Gallbladder removal (only when necessary)
  • No iron supplements

Learn More About Thalassemia Treatments

Visit our Health Library for more on:

Contact the UPMC Adult Sickle Cell Disease Program at 412-692-4724 to schedule an appointment.