Hematology · USMLE Step 1 and Step 2

Thalassemia song

Thalassemia - Alpha vs Beta & Smear Findings, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Thalassemia

Full song on YouTube ↗Spotify ↗

Key points in this song10

Alpha thalassemia results from deletion of alpha-globin genes on chromosome 16; severity scales with number of deletions: 1 (silent carrier), 2 (alpha trait), 3 (HbH disease), 4 (hydrops fetalis with Hb Barts – incompatible with life).
Beta thalassemia results from point mutations in the beta-globin gene on chromosome 11, causing reduced (β+) or absent (β0) beta-chain synthesis.
Beta thalassemia minor (trait) presents as mild microcytic anemia with a normal or elevated RBC count; classically distinguished from iron deficiency by Mentzer index <13.
Beta thalassemia major (Cooley anemia) presents in the first 1–2 years of life when fetal hemoglobin (HbF) declines, causing severe transfusion-dependent hemolytic anemia.
Classic findings in beta thalassemia major include crew-cut skull X-ray (hair-on-end appearance), chipmunk facies, hepatosplenomegaly, and extramedullary hematopoiesis from compensatory marrow expansion.
Hemoglobin electrophoresis in beta thalassemia major shows elevated HbF and HbA2 (>3.5%) with absent or reduced HbA.
HbH disease (3 alpha-gene deletions) produces unstable HbH (β4 tetramers) that precipitate in RBCs, causing hemolytic anemia with splenomegaly and Heinz bodies on crystal violet stain.
Hydrops fetalis (4 alpha-gene deletions) produces Hb Barts (γ4 tetramers) with very high O2 affinity, leading to severe tissue hypoxia, generalized edema, and intrauterine or neonatal death.
Chronic transfusions in beta thalassemia major cause secondary hemochromatosis; iron chelation with deferoxamine or deferasirox is required to prevent cardiac, hepatic, and endocrine damage.
Definitive treatment for transfusion-dependent thalassemia is allogeneic hematopoietic stem cell transplantation; folic acid supplementation is indicated in all thalassemia patients due to increased RBC turnover.