Beta thalassemia

• Most frequent in people from Mediterranean countries, Africa, and southeast Asia where heterozygotes are protected against malaria from it

• There are 2  globin genes, with one being located one of the two chromsome 11s; there are 2 -thalassemia gene variants

  • °, associated with complete absence of  globin chains in the homozygous state

  • ⁺, associated with reduced  globin synthesis in the homozygous state

• Most mutations producing -thalassemias come from point mutations

• Reduced synthesis of  globins leads to decreased formation of HbA

  • The extra, un-paired  chains aggregate and precipitate within RBC precursors as insoluble inclusions

  • The resultant cell membrane damage and impairment of DNA synthesis cause destruction of RBC precursors in the marrow (this is called ineffective erythropoiesis)

  • EPO secretion in response to ineffective erythropoiesis leads to hyperplasia of the marrow, with resultant skeletal abnormalities and extramedullary hematopoiesis; dietary iron absorption is also increased excessively (never give a thalassemia patient Fe; it will make them worse and may lead to hemosiderosis

• Marked hepatomegaly and splenomegaly may result from the hypertrophy of the RES secondary to active erythrophagocytosis and from extramedullary hematopoiesis

• Homozygous individuals for either -thalassemia gene have severe, transfusion-dependent anemias (called -thalassemia major)

  • Severe anemia develops 6-9 months after birth when HbA takes over as the major Hb

  • Peripheral smear findings

    • There is marked anisocytosis (variation in RBC size), microcytosis, and hypochromia

    • Codocytes (target cells; blob of Hb in the middle of the cell), basophilic stippling (from toxic effects of  chains), and fragmented RBCs (schizocytes/spherocytes; these aren’t seen in Fe-deficiency anemia) are common

  • HbF and HbA2 will be increased as the body tries to compensate for the lack of  chains

  • With transfusions and Fe chelators, survival has improved; marrow transplant from and HLA-identical sibling is the only current therapy that offers a cure

• Heterozygotes are usually asymptomatic (-thalassemia trait) or only mildly anemic (-thalassemia minor)

  • Their peripheral smears show mild morphological abnormalities and microcytosis

  • There will be more HbA2 and maybe a little more HbF

  • Recognition of these peeps is important for genetic counseling and looking for cause of anemia in a patient

• -thalassemia intermedia

  • Associated with moderately severe anemia, but not transfusion-dependant

  • May be seen with mild variants of homozygous ^-thalassemia, severe variants of heterozygous thalassemia (or ^), and with double heterozygosity for ^ and 

Category: Medical Subject Notes , Pathology Notes