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Snapshot
  •  A 22-year-old Vietnamese woman presents for a routine gyn exam. Her menstrual cycle is normal, and there is no evidence of other bleeding. Guaiac is negative. Her hemoglobin is at 11 (12-16), RBC is 5.8 (3.5-5.5), and an MCV of 70 (80-100) with a normal RDW of 10. WBC and platelets are normal. Hemoglobin electrophoresis shows an increase in the amount of Hgb A2, and Hgb F.
Introduction

  • Autosomal recessive disease caused by decreased production of hemoglobin
    • may involve mutations in α (α-thalassemia) or β (β-thalassemia) globin gene
  • There are 4 α genes (2 on each chromosome) and 2 β genes that make up three forms of Hgb
    • Hgb A
      • subunits: α,α,β,β
      • 96-98% of adult hemoglobin
    • Hgb A2
      • subunits: α,α,δ,δ
      • present in trace amounts in adults.
    • Hgb F
      • subunits: α,α,γ,γ
      • declines in the first year of life
      • cannot bind 2,3 DPG so has a left-shifted curve
  • α-thalassemia types
    • 1 gene deletion is asymptomatic
    • 2 gene deletion is associated with a mild anemia with RBC hyperplasia
      • called α-thalassemia trait
      • seen in Asians and Africans
        • Asians more commonly have a deletion of two α genes on 1 chromosome (cis deletion)
        • Africans more commonly have a deletion of 1 α gene from each chromosome (trans deletion)
    • 3 gene deletion is associated with severe anemia
    • 4 gene deletion is not compatible with life
      • will cause hydrops fetalis
  • β-thalassemia types
    • 1 gene involvement
      • called β-thalassemia minor 
      • chain may be truncated (β+) or deleted (β0)
      • β/β+ is the most benign form
      • may be caused by mutation in Kozak consensus sequence
    • 2 gene involvement
      • called β-thalassemia major
      • β0/β0 is the most severe form
      • α,α,α,α hemoglobin present
Presentation
  • Symptoms
    • α-thalassemia
      • mild anemia in 2 gene deletion
      • severe anemia in 3 gene deletion
        • symptoms being at birth
    • β-thalassemia 
      • minor form
        • largely asymptomatic
      • intermedia form
        • hypochromic, microcytic anemia 
      • major form
        • severe anemia
        • symptoms begin after several months of life due to initial presence of HbF
        • chipmunk facies
          • secondary to extramedullary hematopoiesis in the skull
  • Physical exam
    • β-thalassemia
      • major form
        • hepatosplenomegaly due to chronic hemolysis, additionally exacerbated by extramedullary hematopoiesis in these organs
Evaluation
  • Peripheral smear
    • β-thalassemia minor
      • target, hypochromic, microcytic cells
    • β-thalassemia major
      • nucleated RBCs
      • target, hypochromic, microcytic cells
  • Hemoglobin gel-electrophoresis
    • α-thalassemia trait
      • normal
    • 3 gene deletion α-thalassemia
      • HbH (β,β,β,β)
    • 4 gene deletion α-thalassemia
      • Hb Barts (γ,γ,γ,γ)
    • β-thalassemia minor 
      • ↑ HbA2, HbF
      • ↓ HbA
    • β-thalassemia major
      • ↑ HbA2, HbF
      • no HbA
  • Imaging
    • β-thalassemia major
      • hair-on-end/crew cut appearance of the skull
        • secondary to extramedullary hematopoiesis in the skull
Treatment
  • β-thalassemia major 
    • frequent transfusions required
      • can cause iron overload and hemochromatosis
Prognosis, Prevention, and Complications
  • β-thalassemia major
    • ↑ risk of B19-mediated aplastic crises
  • Thalassemia trait 
    • protects against malaria

 

 

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