What test do I order to screen for thalassemia traits?

Screening for Thalassemia Traits

The most appropriate initial test to screen for thalassemia traits is a complete blood count (CBC) with red blood cell indices, followed by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) if the CBC shows microcytosis with normal or elevated RBC count.

Initial Screening Algorithm

1. Complete Blood Count (CBC) with RBC indices

   • Look for:
     • Microcytosis (MCV < 80 fL)
     • Normal or elevated RBC count
     • Decreased MCH (mean corpuscular hemoglobin)
     • Normal or slightly decreased hemoglobin

2. Differentiate from iron deficiency

   • Check serum ferritin levels
   • If ferritin is normal or elevated with microcytosis, suspect thalassemia trait
   • If ferritin is low, consider iron deficiency (but note that iron deficiency and thalassemia trait can coexist)

3. Confirmatory testing

   • Hemoglobin electrophoresis or HPLC
   • For beta thalassemia trait: Look for elevated HbA2 (>3.5%) 1, 2
   • For alpha thalassemia trait: Normal HbA2 with microcytosis and normal iron studies

Key Diagnostic Patterns

Beta Thalassemia Trait

• MCV typically < 80 fL
• Normal or elevated RBC count
• Elevated HbA2 (>3.5%) on hemoglobin electrophoresis/HPLC
• Percentage of microcytes typically higher than percentage of hypochromic cells 3
• Normal or elevated ferritin levels

Alpha Thalassemia Trait

• MCV typically < 80 fL
• Normal or elevated RBC count
• Normal HbA2 and HbF levels
• Normal or elevated ferritin levels
• Diagnosis often made by exclusion or molecular genetic testing

Important Considerations

• The RDW (red blood cell distribution width) can help differentiate between thalassemia trait and iron deficiency. In thalassemia trait, RDW is often normal (≤14.0%), while in iron deficiency, it's typically elevated (>14.0%) 1

• Several discriminant formulas can help differentiate between thalassemia trait and iron deficiency when both conditions are suspected:

  • Mentzer index (MCV/RBC): <13 suggests thalassemia trait, >13 suggests iron deficiency 4
  • Green and King formula (MCV² × RDW/Hb × 100): High sensitivity and specificity 4
  • RDWI (RDW × MCV/RBC): Effective in distinguishing beta thalassemia trait from iron deficiency 4

• Molecular genetic testing is the definitive diagnostic method for thalassemia traits but is usually reserved for:

  • Prenatal diagnosis
  • Family studies
  • Cases where hemoglobin analysis is inconclusive 2

• Important pitfall: Iron deficiency can mask elevated HbA2 in beta thalassemia carriers, potentially leading to missed diagnoses 2. Therefore, iron status should always be assessed when thalassemia trait is suspected.

• Another pitfall: Co-inheritance of alpha and beta thalassemia can normalize MCV and MCH, making diagnosis more challenging 2.

By following this systematic approach, thalassemia traits can be effectively identified, allowing for appropriate genetic counseling and management of affected individuals.