Anemia, General Principles


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  1. Microcytic (MCV < 80) àIron-deficiency anemia, sideroblastic anemia,
    anemia of chronic disease, lead poisoning, thalassemia
  2. Normocytic (MCV 80-100) àaplastic anemia, anemia of chronic disease,
    myelofibrosis/bone marrow infiltration, chronic renal failure, hemolytic anemia,
    early stages of iron-deficiency anemia, hemorrhage
  3. Macrocytic (MCV > 100) àmegaloblastic anemia (vitamin B12 and/or folate
    deficiency; drug-induced), liver disease, myelodysplasia, reticulocytosis
    • Clinical features àfatigue, malaise, weakness, poor exercise tolerance,
    tachycardia/palpitations, dyspnea on exertion, dizziness/syncope, chest pain, pallor,
    systolic ejection murmur, wide pulse pressure, orthostatic hypotension
    • Presentation depends on:
  4. Degree of anemia
  5. Rapidity of onset of anemia
  6. Age/health status
    • Best initial diagnostic tests àCBC with RBC indices (e.g. MCV), reticulocyte count,
    blood smear
    • Management àetiology-dependent ± packed RBC transfusion
    • Indications for RBC transfusion à
  7. Acute blood loss > 30% (> 1500-2000 ml)
  8. Hb < 7 g/dL
  9. Hb < 8 g/dL (Hct < 26) + age > 65, cardiovascular/pulmonary disease and/or
    acute bleed
  10. Overtly symptomatic (e.g. chest pain, respiratory distress, CNS symptoms/signs)
    Microcytic Anemia
    Iron-deficiency Anemia
    • Most common cause of anemia
    • Females > Males
    • Etiology:
  11. Chronic blood loss àmost common cause; e.g. GI cancer, PUD, menorrhagia
  12. ↓ dietary intake/malabsorption à e.g. celiac disease, post-gastrectomy, cow’s
    milk diet in infants, achlorhydria
  13. ↑ requirements àe.g. pregnancy, growth spurt
  14. Chronic intravascular hemolysis à hemoglobinuria, hemosiderinuria
    • Promoters of iron absorption à ↓ gastric pH and ascorbic acid
    • Clinical features specific for iron-deficiency anemia à
  15. brittle nails/koilonychia (spoon-shaped nails)
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  16. glossitis/angular cheilitis
  17. pica (craving for non-nutritive substances)
  18. dysphagia (Plummer-Vinson syndrome)
    • Initial lab results (CBC, reticulocyte count, etc.) àlow Hb and/or Hct, low MCV, ↑
    RDW (red blood cell distribution width), ↓ reticulocyte count, possible thrombocytosis
    • Blood smear àhypochromic, microcytic RBCs ± poikilocytosis (abnormal shapes)
    • Best next step à perform iron studies:
  19. ↓ serum ferritin àmost specific laboratory test; lacks sensitivity (falsely
    elevated in inflammatory conditions, liver disease and/or malignancies)
  20. ↓ serum iron
  21. ↑ TIBC (total iron binding capacity)
  22. ↓ transferrin saturation (serum iron/TIBC ratio, expressed as %)
    • Most accurate diagnostic test àbone marrow biopsy + Prussian blue stain
    • Best next step in men > 50 and/or postmenopausal women àcolonoscopy to rule out
    colon cancer
    • Management:
  23. Treatment/correction of any underlying abnormality
  24. Packed RBC transfusion, when indicated (see above)
  25. PO ferrous sulfate (or ferrous gluconate) replacement àcontinued until serum
    ferritin becomes normal, indicating replenishment of iron stores (~ 3-12 months)
  26. Parenteral iron replacement, if malabsorption/intolerance to oral medications
    • Adequate iron replacement indicated by à
  27. Reticulocytosis after ~ 1 week
  28. Rise in Hb of ~ 1g/week
  29. Normalization of Hb after ~ 1 month
    Anemia of Chronic Disease
    • Anemia that accompanies any chronic inflammatory (e.g. RA, IBD, etc.), infectious
    (e.g. TB, bacterial endocarditis, etc.) and/or malignant condition
    • Pathophysiology à
  30. ↓ sensitivity to erythropoietin
  31. Impaired utilization of stored iron à due to ↑ levels of TNF-α and IL-6
    • Clinical features à symptoms/signs of anemia + that of the underlying disease
    • Initial lab results àlow Hb and/or Hct, low or normal MCV, ↓ reticulocyte count,
    normal RDW
    • Blood smear àhypochromic, microcytic or normochromic, normocytic RBCs
    • Best next step à perform iron studies:
  32. ↓ serum iron
  33. ↓ TIBC
  34. Normal transferring saturation
  35. Normal or ↑ serum ferritin
    • Bone marrow biopsy + Prussian blue stain à ↑ stainable iron
    • Management àtreatment/correction of any underlying abnormality ± large doses of
    exogenous erythropoietin ± iron replacement
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    Sideroblastic Anemia
    • A group of disorders of heme (protoporphyrin) synthetic pathway characterized by iron
    accumulation in the perinuclear mitochondria of nucleated RBCs à “ringed”
    sideroblasts
    • May be hereditary (e.g. X-linked; defective δ-aminolevulinic acid (ALA) synthase) or
    acquired (e.g. alcohol, isoniazid, lead poisoning, myelodysplastic syndrome)
    • Sideroblastic anemia associated with myelodysplasia may progress to acute
    myelogenous leukemia (AML)
    • Clinical features of lead poisoning à abdominal colicky pain, peripheral neuropathy
    (e.g. wrist drop, foot drop), encephalopathy, gingival lead lines, developmental delay +
    symptoms/signs of anemia
    • Initial lab results àlow Hb and/or Hct, low MCV, ↓ reticulocyte count
    • Blood smear àdimorphic (both normocytic and microcytic) population of RBCs ±
    basophilic stippling (with lead poisoning)
    • Best next step à perform iron studies:
  36. ↑ serum iron
  37. ↑ serum ferritin
  38. Normal TIBC
  39. ↑ transferrin saturation
    • Most accurate diagnostic test (required for diagnosis) à bone marrow biopsy +
    Prussian blue stain showing ↑ iron stores and ringed sideroblasts
    • Management àremoval of any underlying drug/toxin + trial of vitamin B6/pyridoxine
    (successful in some forms of hereditary sideroblastic anemia) ± lead chelation (e.g.
    EDTA, dimercaprol)
    • Packed RBC transfusion, as indicated