How do you differentiate between alpha thalassemia and beta thalassemia?

Differentiating Alpha Thalassemia from Beta Thalassemia

The key distinction is that beta thalassemia shows elevated HbA2 (>3.5%) and/or elevated HbF on hemoglobin electrophoresis, while alpha thalassemia shows normal or low HbA2 with normal HbF in adults. 1, 2

Initial Screening Approach

Complete Blood Count Findings (Both Conditions)

• Both alpha and beta thalassemia present with microcytic anemia (MCV <80 fL) with normal or elevated ferritin levels, distinguishing them from iron deficiency anemia 3, 1
• The red blood cell count is typically elevated or normal despite the low MCV, a key feature differentiating thalassemia from iron deficiency 2

Hemoglobin Electrophoresis (The Definitive Differentiator)

Beta Thalassemia Trait:

• HbA2 elevated >3.5% (normal is 2.5-3.5%) - this is the hallmark finding 4
• HbF may be mildly elevated (1-5%) 4
• HbA is reduced 4

Alpha Thalassemia Trait:

• HbA2 is normal or slightly decreased 2
• HbF is normal in adults 2
• All hemoglobin fractions appear normal on standard electrophoresis 1, 2

Critical Pitfall

Alpha thalassemia trait cannot be diagnosed by hemoglobin electrophoresis alone in adults because all hemoglobin fractions appear normal - this is the most common diagnostic error. 2 You must proceed to DNA testing when you suspect alpha thalassemia based on microcytic anemia with normal ferritin and normal hemoglobin electrophoresis. 3, 5

Severe Forms (Neonatal Period)

Alpha Thalassemia Major (Hemoglobin Bart's):

• Presents with hydrops fetalis in utero or at birth 3, 2
• Hemoglobin Bart's (γ4) detected on neonatal screening 2
• Typically fatal without intrauterine intervention 3

Beta Thalassemia Major:

• Normal at birth because fetal hemoglobin (HbF) compensates 2
• Symptoms emerge at 6-24 months of age as HbF declines and beta chains are needed 6, 2
• Requires lifelong transfusions starting in early childhood 6, 7

Confirmatory Testing

When Hemoglobin Electrophoresis is Normal but Thalassemia Suspected:

• DNA testing for alpha-globin gene deletions is required to diagnose alpha thalassemia 3, 5
• Most alpha thalassemia results from deletions, while beta thalassemia results from point mutations 4, 5

When Hemoglobin Electrophoresis Shows Elevated HbA2:

• Beta thalassemia is confirmed; DNA testing can identify the specific mutation but is not required for diagnosis 4

Ethnic Background Clues

Alpha thalassemia is most common in:

• Southeast Asian populations (28-55% of non-immune hydrops fetalis cases) 3
• Mediterranean, Middle Eastern, and African populations 3

Beta thalassemia is most common in:

• Mediterranean populations 4
• Middle Eastern and Asian populations 4

Discriminant Formulas (Screening Tool Only)

The Mentzer Index (MCV/RBC) can help screen:

• Mentzer Index <13 suggests thalassemia 8
• Mentzer Index >13 suggests iron deficiency 8
• However, this cannot distinguish alpha from beta thalassemia and requires confirmation with hemoglobin electrophoresis 8