Thalassemia

Thalassemia Introduction

• Thalassemia is a group of inherited blood disorders caused by mutations affecting hemoglobin production.
• Results in reduced production of either alpha or beta globin chains, leading to imbalanced globin synthesis, ineffective erythropoiesis, and hemolysis.
• Categorized into alpha and beta thalassemia based on the affected globin chain.

Types of Thalassemia

1. Alpha 

   • Caused by deletions or mutations in the HBA1 and HBA2
   • Severity depends on the number of affected genes:
     1. Silent Carrier: One gene affected; asymptomatic.
     2. Alpha Thalassemia Trait: Two genes affected; mild anemia.
     3. Hemoglobin H Disease: Three genes affected; moderate to severe anemia.
     4. Hydrops Fetalis: Four genes affected; usually fatal before or shortly after birth.

2. Beta

   • Resulting from mutations in the HBB
   • Classified by severity:
     1. Beta Thalassemia Minor (Trait): One gene affected; mild anemia.
     2. Beta Intermedia: Two genes affected; moderate anemia.
     3. Beta Major (Cooley’s Anemia): Two genes affected; severe anemia requiring regular transfusions.

Pathophysiology

• Imbalanced globin chain production leads to ineffective erythropoiesis and hemolysis.
• Excess unpaired globin chains damage RBC membranes, causing premature cell death.
• Chronic anemia stimulates erythropoietin production and bone marrow expansion, leading to skeletal deformities.

Symptoms

• Symptoms vary based on type and severity:

  1. Mild:

     • Often asymptomatic or mild anemia.

  2. Moderate to Severe:

     • Severe anemia: Fatigue, weakness, pallor.
     • Growth delays and delayed puberty.
     • Bone deformities, especially in the face and skull.
     • Splenomegaly (enlarged spleen).
     • Jaundice from increased hemolysis.
     • Frequent infections.
     • Iron overload leading to organ damage.

Diagnosis of Thalassemia:

• It is diagnosed through:
  1. Complete Blood Count (CBC): Shows low hemoglobin and abnormal RBC indices.
  2. Hemoglobin Electrophoresis: Identifies abnormal hemoglobin types and quantifies hemoglobin fractions.
  3. Genetic Testing: Confirms mutations in globin genes.
  4. Peripheral Blood Smear: Shows microcytic, hypochromic RBCs with target cells and other abnormalities.

Treatment:

• Treatment depends on severity:

  1. Mild Thalassemia:

     • Regular monitoring: usually no treatment needed.

  2. Moderate to Severe:

     1. Regular Blood Transfusions: Maintain hemoglobin levels.
     2. Iron Chelation Therapy: Remove excess iron to prevent organ damage.
     3. Folic Acid Supplements: Support RBC production.
     4. Splenectomy: Removal of the spleen if enlarged.
     5. Bone Marrow Transplant: Potential cure for severe cases.
     6. Gene Therapy: Experimental treatment with curative potential.

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