Thalassemia

Background

  • A group of hereditary disorders resulting in microcytic, hypochromic, hemolytic anemia
  • Most common in Mediterranean, Middle Eastern, African and Southeast Asian population

Clinical Features

  • Categorized depending on globin chain affected or the abnormal Hb produced
    • β-globin gene mutations cause β-thalassemia; ɑ-globin mutations cause ɑ-thalassema

ɑ-Thalassemia Carrier and Trait

  • No clinical symptoms or physical findings
  • Microcytic RBCs and normal Hb level

Hemoglobin H Disease (HbH disease)

  • One ɑ-globin chain gene is still functional
  • Typically presents in neonatal period with severe hypochromic anemia
  • Hypochromic, microcytic anemia with jaundice and hepatosplenomegaly
  • May not require regular transfusions
  • Tranfusions may be necessary in setting of increased oxidative stress or infection which may precipitate hemolysis
  • Note that alpha thalassemia major (Hb Bart) results in hydrops fetalis, and thus is not an adult disease process

β-Thalassemia Minor (β-Thalassemia Trait)

  • Heterozygous for β-globin mutation
  • Mild microcytic anemia
  • Splenomegaly uncommon
  • Microcytosis, hypochromia, basophilic stippling on blood smear
  • Co clinical symptoms

β-Thalassemia Major (Cooley Anemia)

  • Both β-globin genes defective; β-globin chain production severely impaired
  • Typically presents >6mos of life (HbF production replaced with β-globin to form HbA)
  • Hepatosplenomegaly, jaundice, expansion of erythroid marrow causing bone changes and osteoporosis, susceptible to infection
  • Severe anemia requiring regular and lifelong blood transfusions
    • Iron overload secondary to frequent transfusions is etiology of most of morbidity and mortality
  • Low MCV with microcytic and hypochromic RBC

Sickle Cell-β-Thalassemia Disease

  • Gene for sickle Hb is inherited from one parent and gene for β-thalassemia is inherited from the other parent
  • 1 per 1600 African American births
  • Severity depends on type of β-thalassemia gene inherited
    • 80-90% inherit β-thalassemia gene that has some normal β-chain production; these patients have mild hemolytic anemia with near-normal Hb levels, few crises
    • 10-20% inherit β-thalassemia gene that produces no-chains; these patients have severe hemolytic anemia and vaso-occlusive symptoms

Differential Diagnosis

Anemia

RBC Loss

  • Hemorrhage

RBC consumption (Destruction/hemolytic)

Impaired Production (Hypochromic/microcytic)

  • Iron deficiency
  • Anemia of chronic disease
  • Thalassemia
  • Sideroblastic anemia

Aplastic/myelodysplastic (normocytic)

  • Marrow failure
  • Chemicals (e.g. ETOH)
  • Radiation
  • Infection (HIV, parvo)

Megaloblastic (macrocytic)

  • Vitamin B12/folate deficiency
  • Drugs (chemo)
  • HIV

Evaluation

  • CBC
  • CMP
  • Blood smear
  • Reticulocyte count
  • LDH
  • Haptoglobin

Management

  • Identify and discontinue precipitating agent
  • Supportive care
  • Blood transfusions for severe anemia

Disposition

See Also

External Links

References

  • Tintinalli's Emergency Medicine 7th Edition, pg1486-7