Can thalassemia (a genetic disorder affecting hemoglobin production) cause anemia?

Does Thalassemia Cause Anemia?

Yes, thalassemia definitively causes anemia through defective hemoglobin production, resulting in ineffective erythropoiesis, premature red blood cell destruction, and chronic hemolytic anemia. 1, 2

Pathophysiology of Anemia in Thalassemia

Thalassemia represents a group of autosomal recessive hemoglobinopathies where defective synthesis of alpha- or beta-globin chains creates an imbalance in the α/β-globin chain ratio. 1, 2 This fundamental defect triggers a cascade of pathological processes:

• Ineffective erythropoiesis: The imbalanced globin chain production leads to premature destruction of red blood cell precursors in the bone marrow before they can mature into functional erythrocytes. 1, 2

• Chronic hemolytic anemia: Red blood cells that do reach circulation are unstable and undergo premature destruction, further contributing to anemia. 2, 3

• Bone marrow expansion: The body attempts to compensate for severe chronic anemia by expanding bone marrow production and developing extramedullary hematopoiesis, though this compensation is ultimately inadequate. 1

Severity Spectrum of Anemia

The degree of anemia varies dramatically based on the specific genetic mutation:

Thalassemia Major (Transfusion-Dependent)

• Profound, life-threatening anemia develops by 1-2 years of age due to severe reduction or complete absence of β-globin chain production. 4
• Requires lifelong regular red blood cell transfusions (more than 8 transfusion events per year in adults) for survival. 4
• Before modern transfusion therapy, patients typically died by age 10 from complications of severe anemia. 4

Thalassemia Intermedia

• Presents with moderate anemia and variable clinical severity based on specific gene mutations. 4, 1
• Patients present later in life and initially do not require regular transfusions, though many eventually need them to prevent cardiovascular complications. 4

Thalassemia Trait/Minor

• Generally asymptomatic with mild microcytic anemia. 1, 5
• The vast majority of carriers remain asymptomatic, though they exhibit characteristic microcytic hypochromic anemia on peripheral smear. 5

Alpha-Thalassemia Major

• Results in hydrops fetalis with severe intrauterine anemia and hypoxia, often fatal at birth due to the complete absence of functional hemoglobin. 6, 1

Clinical Recognition

Suspect thalassemia in patients presenting with microcytic anemia and normal or elevated ferritin levels, distinguishing it from iron deficiency anemia which presents with low ferritin. 1 Key diagnostic features include:

• Mean corpuscular volume (MCV) <80 fL in thalassemia carriers. 6
• Hemoglobin electrophoresis reveals characteristic patterns (elevated HbA2 in beta-thalassemia trait, Bart's hemoglobin in alpha-thalassemia). 6, 5
• Genetic testing confirms the specific diagnosis. 1

Critical Pitfall

A common and dangerous error is prescribing iron supplementation to thalassemic patients based solely on the presence of anemia. 7 Thalassemic subjects typically have normal or excessive iron stores and do not require iron supplements. 7 In fact, thalassemia patients develop iron overload from both increased gastrointestinal absorption (due to ineffective erythropoiesis) and repeated transfusions, with each transfused unit containing 200-250 mg of elemental iron. 8, 4 Iron supplementation in these patients worsens iron overload and accelerates organ damage, particularly cardiac complications which account for 70% of deaths in transfusion-dependent patients. 8