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Source: Cook K. Anemias. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed January 30, 2017.


  • 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)


  • Macrocytic anemias are a result of quantitative deficiency in hemoglobin synthesis, usually due to iron deficiency or impaired iron utilization.

    • Can be divided into megaloblastic and nonmegaloblastic anemias.


  • Hypoproliferative.

    • Marrow damage.

    • Iron deficiency.

    • Decreased stimulation (renal disease, inflammation, metabolic disease)

  • Maturation disorders.

    • Cytoplasmic defects (thalassemia, iron deficiency, sideroblastic)

    • Nuclear maturation defect (folate deficiency, B12 deficiency, refractory anemia)

  • Hemorrhage/hemolysis.

    • Blood loss.

    • Intravascular hemolysis.

    • Autoimmune disease.

    • Hemoglobinopathy.

    • Metabolic/membrane defect.


  • 1.6 billion people in the world are anemic.

  • Iron deficiency is the leading cause of anemia worldwide.


  • May be asymptomatic or have vague complaints.

  • Patients with B12 deficiency may develop neurologic consequences.


  • Symptoms.

    • Decreased exercise tolerance.

    • Fatigue.

    • Dizziness.

    • Irritability.

    • Weakness.

    • Palpitations.

    • Vertigo.

    • Shortness of breath.

    • Chest pain.

    • Neurological symptoms in vitamin B12 deficiency.

  • Signs.

    • Tachycardia.

    • Pale appearance.

    • Decreased mental acuity.

    • Increased intensity of some cardiac valvular murmurs.

    • Diminished vibratory sense of gait abnormality in vitamin B12 deficiency.

  • Manifestations of iron deficiency anemia (IDA) (Hgb ≤9 g/dL [90 g/L; 5.59 mmol/L])

    • Glossal pain.

    • Smooth tongue.

    • Reduced salivary flow.

    • Pica (compulsive eating of nonfood items)

    • Pagophagia (compulsive eating of ice)

  • Folate deficiency is typically macrocytic but without neurological symptoms (unlike B12)




  • Complete blood count (CBC) (Table 1)

    • Focus on Hb, hematocrit (Hct), and RBC indices.

    • May initially be normal and then decrease as anemia progresses.

  • Serum iron (low with IDA and anemia of inflammation (AI))

  • Ferritin.

    • Low with IDA and normal to increased in AI

    • Earliest and most sensitive indicator of iron deficiency.

    • Interpret in conjunction with transferring saturation and total iron-binding capacity (TIBC)

  • TIBC (high with IDA and low or normal in AI)

  • Mean cell volume is elevated in vitamin B12 deficiency and folate deficiency.

  • Vitamin B12 and folate levels are low in their respective types of anemia.

  • Homocysteine is elevated in vitamin B12 deficiency and folate deficiency.

  • Methylmalonic acid is elevated in vitamin B12 deficiency.

TABLE 1.aNormal Hematologic Values...

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