What is the initial workup for a patient suspected of having thalassemia?

Initial Workup for Suspected Thalassemia

The initial workup for a patient suspected of having thalassemia should include a complete blood count (CBC) with differential, peripheral blood smear examination, hemoglobin electrophoresis, and genetic testing based on preliminary findings. 1

Step 1: Initial Laboratory Testing

• Complete Blood Count (CBC): Essential first step to identify microcytic anemia with normal or elevated red blood cell count

  • Look for decreased MCV (< 80 fL)
  • Decreased MCH
  • Normal or elevated RBC count (distinguishes from iron deficiency)
  • Hemoglobin levels (variable depending on severity)

• Peripheral Blood Smear: Evaluate for characteristic morphological changes

  • Microcytosis
  • Hypochromia
  • Target cells
  • Basophilic stippling
  • Nucleated RBCs (in severe cases)

Step 2: Iron Studies

• Serum Ferritin: Normal or elevated (distinguishes from iron deficiency anemia)
• Serum Iron and TIBC: To rule out iron deficiency
• Transferrin Saturation: Usually normal or elevated in thalassemia

Step 3: Hemoglobin Analysis

• Hemoglobin Electrophoresis: Critical for diagnosis and classification 2
• High-Performance Liquid Chromatography (HPLC): More sensitive method to detect and quantify abnormal hemoglobins
• Capillary Electrophoresis: Alternative method for hemoglobin analysis
• Mass Spectrometry: Advanced technique for precise hemoglobin variant identification

Step 4: Molecular Genetic Testing

• DNA Analysis: Based on initial findings to confirm diagnosis 2
  • For α-thalassemia: Testing for common deletions in α-globin genes
  • For β-thalassemia: Sequencing of β-globin gene for mutations
  • Multiplex PCR or gap-PCR for common deletions
  • Next-generation sequencing for comprehensive analysis

Special Considerations

Family Testing

• Mean Corpuscular Volume (MCV) of parents: If < 80 fL, suggests carrier status 3
• Consider testing siblings and other family members

Ethnic Background Assessment

• Higher prevalence in Mediterranean, Middle Eastern, African, and Southeast Asian populations
• Specific mutations may be more common in certain ethnic groups

Pregnancy Considerations

• For pregnant women or couples planning pregnancy with family history:
  • Both partners should be tested
  • Consider genetic counseling
  • Prenatal diagnosis options if both parents are carriers 2

Diagnostic Algorithm

1. Initial Suspicion: Microcytic anemia with normal/high RBC count and normal/elevated ferritin
2. Confirm Iron Status: Rule out iron deficiency
3. Hemoglobin Analysis: Identify abnormal hemoglobin patterns
4. Genetic Testing: Confirm specific mutations or deletions
5. Family Testing: Screen at-risk family members

Common Pitfalls to Avoid

• Misdiagnosing as iron deficiency: Always check ferritin levels and iron studies
• Incomplete hemoglobin analysis: Some hemoglobin variants require specialized testing
• Overlooking combined disorders: Thalassemia can coexist with other hemoglobinopathies or iron deficiency
• Failure to consider alpha thalassemia: Normal hemoglobin electrophoresis doesn't rule out alpha thalassemia
• Inadequate family screening: Important for genetic counseling and prevention

By following this systematic approach, clinicians can accurately diagnose thalassemia, determine its severity, and develop appropriate management strategies to reduce morbidity and mortality associated with this condition.