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Thalassemia

Thalassemia is a group of inherited hemoglobin disorders caused by reduced or absent production of alpha or beta globin chains. This leads to microcytic anemia, ineffective erythropoiesis, and increased red blood cell destruction

Also called

Mediterranean Anemia

ICD-10

D56.9

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Thalassemia occurs when the body produces insufficient amounts of one of the globin chains needed to make hemoglobin. The resulting red blood cells are small, pale, and easily destroyed, causing chronic anemia. Severe disease can lead to bone marrow expansion, hepatosplenomegaly, growth problems, and iron overload.

Etiology & Risk Factors

-Etiology

It is caused by inherited mutations or deletions in globin genes, resulting in reduced or absent production of globin chains.

–Alpha Thalassemia

Caused by abnormalities involving the alpha-globin genes on chromosome 16.

Severity depends mainly on the number of affected alpha-globin genes.

–Beta Thalassemia

Caused by mutations affecting the beta-globin gene on chromosome 11.

Mutations may cause:

  • Reduced beta-globin production

  • Absent beta-globin production

-Types

Alpha Thalassemia

  • Silent carrier

  • Alpha thalassemia trait

  • Hemoglobin H disease

  • Hydrops fetalis with Hb Bart’s

Beta Thalassemia

  • Beta thalassemia trait

  • Beta thalassemia intermedia

  • Beta thalassemia major

-Risk Factors

  • Family history

  • Parents carrying thalassemia mutations

  • Consanguinity

  • Mediterranean ancestry

  • Middle Eastern ancestry

  • South Asian ancestry

  • Southeast Asian ancestry

  • African ancestry

Pathophysiology

Globin gene mutation → reduced globin-chain synthesis → imbalance between globin chains → ineffective hemoglobin production → ineffective erythropoiesis and red blood cell destruction → chronic anemia → increased erythropoietin production → bone marrow expansion and extramedullary hematopoiesis → hepatosplenomegaly and skeletal changes → chronic anemia and transfusion therapy may lead to iron overload.

Clinical Presentation

-Symptoms

Mild disease may be asymptomatic.

Moderate or severe disease may cause:

  • Fatigue

  • Weakness

  • Pallor

  • Shortness of breath

  • Dizziness

  • Poor growth

  • Delayed puberty

  • Abdominal fullness

  • Exercise intolerance

-Signs

  • Pallor

  • Jaundice

  • Hepatomegaly

  • Splenomegaly

  • Growth retardation

  • Skeletal abnormalities in severe untreated disease

  • Signs of iron overload in chronically transfused patients

-Severe Disease

Beta thalassemia major may present during infancy with:

  • Severe anemia

  • Failure to thrive

  • Feeding difficulties

  • Recurrent infections

  • Marked hepatosplenomegaly

History Taking

-Ask about:

  • Fatigue
  • Pallor
  • Exercise intolerance
  • Jaundice
  • Recurrent infections
  • Growth and development
  • Delayed puberty
  • Abdominal fullness
  • Previous blood transfusions
  • Iron chelation therapy
  • Family history
  • Consanguinity
  • Previous diagnosis of anemia
  • Dietary history
  • Previous iron therapy

Physical Examination

-General Examination

Look for:

  • Pallor

  • Jaundice

  • Growth retardation

  • Delayed puberty

  • Signs of chronic anemia

-Abdominal Examination

Assess for:

  • Splenomegaly

  • Hepatomegaly

-Skeletal Examination

In severe untreated disease, look for:

  • Frontal bossing

  • Maxillary enlargement

  • Facial bone changes

  • Bone deformities

-Cardiovascular Examination

Assess for:

  • Tachycardia

  • Flow murmur

  • Signs of heart failure

  • Cardiac complications from iron overload

Investigations

-Complete Blood Count

Typical findings:

  • Low hemoglobin

  • Marked microcytosis

  • Low MCV

  • Low MCH

  • RBC count may be relatively high, particularly in thalassemia trait

  • Variable reticulocytosis

-Peripheral Blood Film

May show:

  • Microcytosis

  • Hypochromia

  • Target cells

  • Anisopoikilocytosis

  • Basophilic stippling

  • Nucleated red blood cells in severe disease

-Iron Studies

Usually:

  • Ferritin normal or increased

  • Serum iron normal or increased

–Iron studies are important to distinguish thalassemia from iron deficiency anemia.

-Hemoglobin Analysis

Hemoglobin Electrophoresis / HPLC: Useful for identifying abnormal hemoglobin patterns.

In beta thalassemia trait:

  • HbA2 is usually increased

  • HbF may be mildly increased

In severe beta thalassemia:

  • HbF is markedly increased

  • HbA may be reduced or absent depending on the genotype

Alpha thalassemia may have a normal adult hemoglobin electrophoresis, particularly in the trait state.

-Genetic Testing

Useful for:

  • Confirming the diagnosis

  • Identifying specific mutations

  • Prenatal diagnosis

  • Family screening

Additional Investigations in Severe Disease

  • Liver function tests

  • Ferritin

  • Transferrin saturation

  • Cardiac MRI for iron overload

  • Liver MRI for iron concentration

  • Endocrine assessment

  • Bone density assessment

Diagnosis

-Diagnosis is based on:

  • Chronic microcytic anemia
  • Peripheral blood film findings
  • Iron studies
  • Hemoglobin electrophoresis or HPLC
  • Genetic testing when required
  • Family history
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Management

-Thalassemia Trait

Usually requires:

  • No specific treatment

  • Avoid unnecessary iron therapy

  • Genetic counseling

  • Screening of partners when appropriate

-Severe Thalassemia

1. Regular Blood Transfusion

Used for severe anemia and transfusion-dependent disease.

Goals include:

  • Maintaining adequate hemoglobin

  • Suppressing ineffective erythropoiesis

  • Reducing skeletal complications

  • Supporting normal growth and development

2. Iron Chelation

Repeated transfusions cause iron overload.

Chelation options include:

  • Deferasirox

  • Deferoxamine

  • Deferiprone

Treatment is guided by iron burden and organ involvement.

3. Folic Acid

May be used in patients with increased erythropoiesis when clinically appropriate.

4. Splenectomy

May be considered in selected patients with:

  • Severe hypersplenism

  • Increasing transfusion requirements

  • Symptomatic splenomegaly

5. Luspatercept

May be used in selected adults with transfusion-dependent beta thalassemia to reduce transfusion requirements.

6. Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation can be curative, particularly when performed in appropriately selected younger patients.

7. Gene Therapy

Gene-based therapies are available for selected patients with transfusion-dependent beta thalassemia in appropriate specialist settings.

Complications

  • Severe chronic anemia
  • Growth retardation
  • Delayed puberty
  • Hepatosplenomegaly
  • Skeletal abnormalities
  • Gallstones
  • Extramedullary hematopoiesis
  • Iron overload
  • Cardiomyopathy
  • Liver fibrosis
  • Endocrine dysfunction
  • Diabetes mellitus
  • Hypogonadism
  • Osteoporosis
  • Increased infection risk
  • Transfusion reactions
  • Alloimmunization

Prognosis

Prognosis varies according to the type and severity of thalassemia. Patients with thalassemia trait usually have a normal life expectancy, while severe transfusion-dependent disease requires lifelong specialist care. Modern transfusion therapy, iron chelation, stem cell transplantation, and newer gene-based treatments have significantly improved outcomes.

Key Points / Clinical Pearls

  • Thalassemia is an inherited hemoglobin disorder.
  • It results from reduced production of alpha or beta globin chains.
  • It causes microcytic, hypochromic anemia.
  • Thalassemia trait is often mild or asymptomatic.
  • Severe disease causes chronic anemia and hepatosplenomegaly.
  • The red blood cell count may be relatively high despite microcytosis.
  • Iron studies are usually normal unless iron deficiency is also present.
  • Hemoglobin electrophoresis is useful, particularly for beta thalassemia.
  • Genetic testing is important in selected cases.
  • Severe disease may require regular blood transfusions.
  • Repeated transfusions can cause iron overload.
  • Iron chelation is essential when significant iron overload develops.
  • Hematopoietic stem cell transplantation can be curative in suitable patients.