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Source: Cook K, Ineck BA, Lyond WL. Anemias. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Accessed June 12, 2012.

  • Pernicious anemia

  • Decreased oxygen-carrying capacity of blood characterized by a decrease in hemoglobin (Hb) or red blood cells (RBCs)
  • World Health Organization (WHO definition)
    • Men: Hb <13 g/dL (<130 g/L; <8.07 mmol/L)
    • Women: Hb <12 g/dL (<120 g/L; <7.45 mmol/L)

  • Major causes of vitamin B12 deficiency
    • Inadequate dietary intake
    • Decreased absorption
      • Pernicious anemia: Deficiency of intrinsic factor can cause decreased absorption of vitamin B12
      • Chronic gastritis due to Helicobacter pylori infection
    • Inadequate utilization

  • Vitamin B12 functions
    • With folate in the synthesis of building blocks for DNA and RNA
    • In maintaining the integrity of the neurologic system
    • In fatty acid biosynthesis and energy production
  • Vitamin B12 deficiency develops over several years of deprivation because of efficient enterohepatic circulation and body stores.
  • Macrocytic, megaloblastic anemia

  • Increasing age
  • Use of gastric acid–suppressing agents

  • Neurologic findings often precede hematologic findings and may occur in the absence of anemia.

Signs and Symptoms

  • Neurologic findings
    • Numbness and paraesthesias
    • Peripheral neuropathy
    • Ataxia
    • Diminished vibratory sense
    • Decreased proprioception
    • Vision changes if optic nerve is involved
  • Psychiatric findings
    • Irritability
    • Personality changes
    • Memory impairment
    • Depression
    • Psychosis
  • In children: prolonged deficiency can lead to poor brain development
  • Pallor
  • Mild icterus
  • Glossitis

Means of Confirmation and Diagnosis

Laboratory Tests

  • CBC
  • Reticulocyte count
  • Vitamin B12 serum levels
    • <150 pg/mL (<111 pmol/L), together with appropriate peripheral smear and clinical symptoms, is diagnostic of vitamin B12–deficiency anemia.
  • Serum homocysteine
  • Serum methylmalonic acid (MMA)
    • Elevations >1000 nmol/L can confirm diagnosis.

Diagnostic Procedures

  • Shilling test to help identify intrinsic factor deficiency
  • Bone marrow aspirate

Differential Diagnosis

  • Folic acid deficiency (another cause of megaloblastic anemia)
  • Myelodysplastic syndrome (another cause of macrocytic anemia)
  • Other causes of neurologic symptoms

  • Reversal of hematologic manifestations
  • Replacement of body stores
  • Prevention or resolution of neurologic manifestations

  • Early treatment is critical. Neurologic damage may be irreversible if vitamin B12 deficiency not detected and corrected within months.
  • Counsel patients on types of food high in vitamin B12.

  • Oral vitamin B12 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because alternate vitamin B12 absorption pathway is independent of intrinsic factor.
    • Initiate oral cobalamin 1–2 mg daily for 1–2 weeks, followed by 1 mg daily.
  • Parenteral vitamin B12 may also be used. Recommended regimens:
    • Cyanocobalamin 1000 mcg IM daily for 1 week, then weekly for 1 month, and then monthly.
    • ...

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