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

β-Thalassemia Minor (β-Thalassemia Trait)

• heterozygous for β-globin mutation
• mild microcytic anemia
• splenomegaly uncommon
• microcytosis, hypochromia, basophilic stippling on blood smear
• no 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)

• Hereditary
  • Sickle cell disease
  • Glucose-6-phosphate deficiency
• Acquired
• Microangiopathic Hemolytic Anemia (MAHA)
• Autoimmune hemolytic anemia

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

See Also

• Anemia

References

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

Authors

Kaoru Itakura, Claire, Ross Donaldson