Beta thalassemia

on 4.3.09 with 0 comments

  • 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



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