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  • RBC ↓, evidenced by hemoglobin (Hb) (<13.5g/dL ♂, <12g/dL ♀) or hematocrit (Hct) (<41% ♂, <36% ♀)
  • Expert opinions vary on precise definition of anemia; Hb & Hct are volume dependent


3 Primary Etiologies


  1. Blood loss: trauma, menstruation, GI bleeding (NSAIDs), blood donation, parasites

  2. Inadequate RBC production: nutritional deficiency (B12, folate, iron), endocrine abnormalities (thyroid, EPO, hypogonadism), malignancy, etc.

  3. RBC destruction: hemolysis—genetic or acquired


Classification Based on Average RBC Size


  • Signs/symptoms: result of impaired O2 delivery to tissues; perfusion can be maintained down to ∼Hb 8–9g/dL
    • Fatigue, SOB/DOE, palpitations, headache, confusion, mental slowing, change in stool habits (GI bleeding), tachycardia, hypotension, pallor, splenomegaly, jaundice
  • Initial evaluation: Hb/Hct, MCV, RDW, reticulocyte count, WBC, platelet count, peripheral smear
    • Macrocytic anemia: B12 & folate deficiencies; result in indistinguishable anemias
      • B12 deficiency: RDA 2.4mcg/d—macrocytosis can precede anemia by several months
      • Complications: myelopathy, ataxia, paresthesia, loss of proprioception & vibratory sensation, cognitive impairment, confusion, depression, psychosis, osteoporosis
      • Efficient use of B12 requires a working gut, gastric acid & pepsin to free B12 from food proteins in the gut, & intrinsic factor (IF) to facilitate absorption in the ileum
        • Pernicious anemia (PA) (loss of intrinsic factor) is common cause of B12 deficiency; ∼1% of ingested B12 is passively absorbed without IF
      • Typical diet provides adequate B12; most Americans ≥2–5y of stores (highly conserved) (Neurology 1995;45:1435)
        • At risk: elderly (achlorhydria, dietary deficiency), strict vegetarians/vegans, GI disease/surgery, pancreatic insufficiency, PPI use, metformin use (South Med J 2010;103:265)
      • Causes functional folate deficiency (folate trap)
      • B12 serum concentrations vary with age & gender, making it less than optimal for determining deficiency (Food & Nutrition Bulletin 2008;29:S67)
        • Accumulation of methylmalonic acid (MMA) specific to B12 deficiency
          • Fasting urine MMA 99% specific for diagnosing B12 deficiency (Ann Intern Med 1987;106:707); serum MMA affected by renal status (Clin Chem 2000;46:1277)
      • Folate deficiency: RDA 400mcg/d—associated with hyperhomo–cysteinemia & periconceptually with neural tube defects (Lancet 1997;350:1666)
        • RBC folate: may be more reliable indicator of deficiency than serum folate in acutely ill → serum levels susceptible to dietary change, while RBC levels reflect span of RBC life (Am J Clin Nutr 2011;94:303S); both ↑ with age (J Nutr 2006;136:153); this may make interpreting results problematic
        • Homocysteine accumulates in B12 & folate deficiencies; serum homocysteine concentration may be a better indicator of folate deficiency than direct folate measurements (JAMA 1993;270:2693)
    • Microcytic anemia: iron-deficiency anemia (IDA)
      • Iron RDA: ♂ & postmenopausal ♀ ∼8mg/d; menstruating ♀∼18mg/d
        • No mechanism for excretion ∴ regulated by GI tract absorption (↓); heme iron (animal source) absorbed better than nonheme (plant source)
        • Serum iron sensitive to daily intake; diurnal variation (Am J Clin Pathol 2002;117:802)
        • Ferritin: best indicator of IDA (J Nutr 2005;135:1974); acute phase reactant; ↑ with inflammation (Am J Clin Nutr 2010;92:546), true iron deficiency; <15ng/mL without infection, <30ng/mL during infection (WHO Vitamin & Mineral Nutrition Information System 2011)
        • Transferrin saturation (TSAT): ...

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