Hematology · Microcytic Anemia
The facts most likely to be tested
Beta thalassemia is caused by mutations in the HBB gene leading to decreased or absent beta-globin chain synthesis.
Patients with Beta Thalassemia Minor (trait) typically present with asymptomatic microcytic anemia and an elevated HbA2 level on hemoglobin electrophoresis.
Beta Thalassemia Major (Cooley's anemia) presents in infancy with severe hemolytic anemia, failure to thrive, and hepatosplenomegaly.
Chronic hemolysis and ineffective erythropoiesis in severe cases lead to extramedullary hematopoiesis, causing 'chipmunk facies' and 'crew-cut' appearance on skull X-ray.
Peripheral blood smears in beta thalassemia demonstrate target cells, basophilic stippling, and microcytic, hypochromic RBCs.
The definitive diagnostic test for beta thalassemia is hemoglobin electrophoresis, which reveals elevated HbA2 and/or HbF.
Patients with transfusion-dependent beta thalassemia require lifelong iron chelation therapy (e.g., deferoxamine) to prevent secondary hemochromatosis.
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A 14-month-old male is brought to the clinic for poor growth and pallor. Physical examination reveals frontal bossing, maxillary hyperplasia, and a palpable spleen 4 cm below the costal margin. Laboratory studies show a hemoglobin of 7.2 g/dL, MCV of 62 fL, and a peripheral smear showing target cells and basophilic stippling. Hemoglobin electrophoresis shows a significant elevation of HbF and a decrease in HbA.
What is the most likely diagnosis?
Beta Thalassemia Major
The patient's clinical presentation of severe anemia, skeletal deformities from marrow expansion, and characteristic electrophoresis findings confirm Beta Thalassemia Major, as described in bets 3, 4, and 6.
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High yield triage
Etiology / Epidemiology
Autosomal recessive defect in beta-globin chain synthesis; highly prevalent in Mediterranean, African, and Southeast Asian populations.
Clinical Manifestations
Severe anemia, chipmunk facies, and hepatosplenomegaly due to ineffective erythropoiesis.
Diagnosis
Hemoglobin electrophoresis is the gold standard; shows elevated HbA2 and HbF.
Treatment
Regular transfusions and deferoxamine for iron overload; avoid iron supplements.
Prognosis
High risk of iron overload leading to cardiac failure; requires lifelong monitoring.
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Epidemiology & Etiology
Genetic mutation results in reduced or absent beta-globin chains. Most common in individuals of Mediterranean descent. Inheritance is autosomal recessive, with severity ranging from minor (trait) to major (Cooley's anemia).
Pertinent Anatomy
Defect occurs in the beta-globin gene cluster on chromosome 11. Ineffective erythropoiesis occurs primarily in the bone marrow and extramedullary sites like the spleen.
Pathophysiology
Decreased beta-globin leads to excess alpha-globin chains, which precipitate and damage red cell membranes. This causes premature hemolysis and ineffective erythropoiesis. The body compensates with massive marrow expansion, leading to skeletal deformities and extramedullary hematopoiesis.
Clinical Manifestations
Patients present with severe microcytic anemia, jaundice, and chipmunk facies due to maxillary overgrowth. Physical exam reveals hepatosplenomegaly and growth retardation. Red flag: severe anemia presenting in the first year of life requires immediate evaluation.
Diagnosis
Hemoglobin electrophoresis is the diagnostic test of choice. Beta-thalassemia minor shows elevated HbA2 (>3.5%). Beta-thalassemia major shows near-total absence of HbA and significant elevation of HbF.
Treatment
Management requires chronic blood transfusions to maintain hemoglobin levels. Iron supplements are contraindicated as they exacerbate iron overload. Deferoxamine is the first-line iron chelator used to prevent organ damage from hemosiderosis.
Prognosis
Primary cause of mortality is cardiac failure secondary to iron overload. Patients require regular monitoring of ferritin levels and cardiac function to manage the complications of chronic transfusion therapy.
Differential Diagnosis
Iron Deficiency Anemia: low ferritin, high TIBC
Alpha Thalassemia: normal Hb electrophoresis
Sideroblastic Anemia: ringed sideroblasts on bone marrow biopsy
Lead Poisoning: basophilic stippling on peripheral smear
Anemia of Chronic Disease: normal/high ferritin, low TIBC