Thalassemia Diagnosis and Management

Introduction to Thalassemia

Beta thalassemia results from reduced or absent synthesis of beta-globin chains due to mutations in the HBB gene on chromosome 11, with humans having only two beta-globin genes, and the condition is caused predominantly by point mutations, including single nucleotide substitutions, small deletions, or insertions 1
Even heterozygous mutations in the HBB gene cause detectable hematologic changes, known as beta thalassemia trait 2

Infants with beta thalassemia are healthy at birth because fetal hemoglobin does not require beta-globin chains 1
Symptoms of beta thalassemia emerge at approximately 1-2 years of age as fetal hemoglobin production declines and the switch to adult hemoglobin occurs 3 1
Beta thalassemia major becomes life-threatening by age 1-2 years, requiring lifelong transfusions starting before age 2 3 1
Beta thalassemia trait causes persistent microcytic anemia that does not respond to iron supplementation 2

Beta thalassemia major requires more than 8 transfusion events per year in adults over 16 years 3 1
Before modern chelation therapy, patients with beta thalassemia major died by age 10 from cardiac complications; now survival into the 7th decade is possible with optimal care 4 3
Cardiac iron loading accounts for approximately 70% of mortality in transfusion-dependent patients 3 1
Each transfused unit contains approximately 200-250 mg of elemental iron, necessitating lifelong iron chelation therapy 5 3

Both alpha and beta thalassemia present with microcytic hypochromic anemia with normal or elevated ferritin levels 2
Mean corpuscular volume (MCV) is typically <80 fL in patients with thalassemia 2
Genetic testing confirms the diagnosis for both alpha and beta thalassemia 2

Do not prescribe iron supplementation to patients with confirmed thalassemia trait—it provides no benefit and may contribute to unnecessary iron accumulation 2
In pregnant women of Mediterranean, Middle Eastern, Southeast Asian, or African ancestry with persistent mild anemia unresponsive to prenatal iron, evaluate with MCV, RDW, and hemoglobin electrophoresis 2
Always check serum ferritin to rule out concurrent iron deficiency before attributing microcytic anemia solely to thalassemia trait 2
Failure to consider ethnicity leads to missed diagnoses, as thalassemias are significantly more common in populations from malaria-endemic regions 2