From the Guidelines
Thalassemia patients typically exhibit moderate to severe microcytosis, with mean corpuscular volume (MCV) values often below 75 fL. The degree of microcytosis in thalassemia is a critical aspect of the disease, as it reflects the severity of the disorder. According to the study by 1, β-thalassemia major is a genetic condition characterized by severe reduction or absent production of the β-globin chain constituent of hemoglobin (Hb) A, leading to ineffective erythropoiesis and profound anemia.
Key Characteristics of Microcytosis in Thalassemia
- The microcytosis in thalassemia is due to defective hemoglobin synthesis, resulting in smaller red blood cells with reduced hemoglobin content.
- The degree of microcytosis generally correlates with the severity of the thalassemia, with beta thalassemia major patients showing more pronounced microcytosis than those with thalassemia minor or alpha thalassemia trait.
- Unlike iron deficiency anemia, the microcytosis in thalassemia persists despite iron supplementation and is accompanied by other characteristic findings such as elevated red blood cell count, target cells on peripheral smear, and normal or increased red cell distribution width (RDW).
Diagnostic Considerations
- Hemoglobin electrophoresis is necessary for definitive diagnosis, as it reveals the abnormal hemoglobin patterns characteristic of different thalassemia types.
- The persistent microcytosis serves as an important diagnostic clue that helps distinguish thalassemia from other causes of anemia, as noted in the context of β-thalassemia major by 1.
From the Research
Degree of Microcytosis in Thalassemia
- The degree of microcytosis in patients with thalassemia can be measured by the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels 2, 3.
- In beta-thalassemia carriers, MCV levels are typically between 60-70 fL, and MCH levels are between 19-23 pg 2.
- In alpha-thalassemia carriers, MCV and MCH levels may be slightly to moderately reduced, but the exact values can vary 2, 3.
- A study found that MCH exhibited the highest sensitivity, specificity, and diagnostic accuracy for alpha-thalassemia screening, with a cutoff value of < 27 pg 3.
- The combination of MCV, MCH, and hemoglobin A2 (HbA2) levels can be used to screen for alpha-thalassemia, with a sensitivity of 72.6% and specificity of 89.0% 3.
Comparison with Iron Deficiency Anemia
- Microcytosis can also be caused by iron deficiency anemia, which can be distinguished from thalassemia by serum ferritin measurement and other laboratory tests 4, 5.
- Red cell distribution width (RDW) can be used to differentiate iron deficiency anemia from thalassemia trait, but its utility is limited due to overlapping values 6.
- A study found that RDW had a sensitivity of 67.9% and specificity of 25% for detecting iron deficiency anemia, and 71.42% sensitivity and 40% specificity for detecting microcytic anemia 6.
Laboratory Diagnosis
- Laboratory diagnosis of thalassemia involves hematological tests, including red cell indices and morphology, followed by separation and measurement of Hb fractions 2.
- Molecular analysis is necessary to confirm the diagnosis of alpha-thalassemia carrier status and to predict severe transfusion-dependent and intermediate-to-mild non-transfusion-dependent cases 2.
- DNA analysis on chorionic villi can be used for prenatal diagnosis of thalassemia 2.