Differences between etiologies of anemia resulting from impaired RBC production

• Stem cell failure

  • Aplastic anemia

    • Pancytopenia with marked bone marrow hypoplasia; splenomegaly and reticulocytosis is characteristically absent (because problems are in the bone marrow)

    • Patients are at risk for bacterial infections (due to neutropenia), bleeding (from thrombopenia), and acute leukemia (this is a stem cell thing)

    • Causes

      • Most are idiopathic (65%)

      • Most of the cases of known etiology follow exposure to myelotoxic drugs

      • Other known causes are insecticides, whole body irradiation, and infections like HIV, CMV, EBV, VZV, parvovirus B19, and viral hepatitis

    • If they are known, w/d of causative agents may be curative; marrow transplantation has been effective in younger patients, whereas older adults may benefit from immunosuppression

    • Proposed mechanisms

      • Immunologically-mediated suppression of marrow stem cells via the secretion of inhibitory cytokines like IFN- and TNF- by activated T cells (T cell response thought to be due to antigenic alteration of stem cells after exposure to environmental insult)

      • Intrinsic abnormality of stem cells from genetic damage (supported by occasional transformation to acute leukemia)

      • The environmental kind is more responsive to steroids

    • Hereditary bone marrow aplasia (Faconi’s anemia)

      • Rare, AR syndrome characterized by defects in DNA repair

      • May also see hypoplasia of the spleen, kidneys, and bones (especially of the thumbs and radii)

      • Kids with this are at high risk of developing leukemia and carcinomas

      • Bone marrow transplant will cure anemia, but won’t decrease the risk for CA

  • Pure red cell aplasia

    • Acute forms may be seen with chronic pre-existing hemolytic anemia (infection shuts down the overworked marrow) or as a drug or infection-related d/o (these 2 affect previously normal marrow); these are usually self-limited and referred to as transient erythroblastopenia of childhood

    • Chronic forms

      • Diamond-Blackfan syndrome: idiopathic and hereditary; marrow transplant is the only treatment

      • Associated with neoplasms like leukemia of large granular lymphocytes and thymoma (resection of thymoma may be curative in up to ½ of patients; in the others do plasmapheresis or immunosuppressive therapy)

  • Anemia of renal failure

    • Comes from decreased EPO production or from uremia and platelet dysfunction (latter may lead to bleeding and Fe deficiency)

    • Recombinant EPO is helpful

  • Anemia of endocrine d/o

    • Usually mild and asymptomatic

    • Seen with d/o of the thyroid, adrenal, nads, and pituitary

• D/o of erythroblast proliferation and maturation

  • Megaloblastic anemias

  • Myelodysplastic syndromes

  • Fe deficiency
    

  • Sideroblastic anemias

    • Come from an Fe utilization defect with abnormal accumulation of hemosiderin in “ring sideroblasts” (Fe accumulates in the mitochondria around the nucleus)

    • May be idiopathic, hereditary, or drug-induced

  • Anemias of chronic disease
    

  • Myelophthisic anemia
    

Category: Medical Subject Notes , Pathology Notes