General Principles


Anemia is defined as a decrease in circulating red blood cell (RBC) mass, the usual criteria in adults being hemoglobin (Hgb) <12 g/dL or hematocrit (Hct) <36% for nonpregnant women and Hgb <13 g/dL or Hct <39% in men.


Anemia can be broadly classified into three etiologic groups: blood loss (acute or chronic), decreased RBC production, and increased RBC destruction (hemolysis). Anemia can also be categorized by RBC size as microcytic, normocytic, or macrocytic.

Clinical Presentation

Common signs and symptoms of anemia include pallor, tachycardia, hypotension, dizziness, tinnitus, headaches, decreased cognitive ability, fatigue, and weakness. Atrophic glossitis, angular cheilosis, koilonychia (spoon nails), and brittle nails are more common in severe, long-standing anemia. Patients may also experience reduced exercise tolerance, dyspnea on exertion, and heart failure. High-output heart failure and hypovolemic shock may be seen in acute, severe cases.

Diagnostic Testing


  • The complete blood count (CBC), reticulocyte count, and inspection of the peripheral smear will guide further laboratory testing because they provide a morphologic classification and assessment of RBC production.
  • The Hgb level is a measure of the concentration of Hgb in blood as expressed in grams per deciliter (g/dL), whereas the Hct is the percentage of the blood that is RBCs. Hgb and Hct are unreliable indicators of red cell mass in the setting of rapid shifts of intravascular volume (i.e., an acute bleed).
  • The most useful red cell indices include the following:
    • Mean cellular volume (MCV): Measures the mean volume of the RBCs.
      • Microcytic: MCV <80 fL
      • Normocytic: MCV 80–96 fL
      • Macrocytic: MCV >96 fL
    • Red cell distribution width (RDW): Reflects the variability in the volume of the RBCs and is proportional to the standard deviation of the MCV. An elevated RDW indicates an increased variability in RBC size, which is a nonspecific but important finding in anemic patients (i.e., increased reticulocytes can cause elevation in RDW as they are larger than mature RBCs).
    • Mean cellular Hgb: Defines the concentration of Hgb in each cell, and an elevated level is often indicative of spherocytes or a hemoglobinopathy.
  • The relative reticulocyte count measures the percentage of immature red cells in the blood and reflects production of RBCs in the bone marrow (BM).
    • A normal RBC has a life span of approximately 120 days, and the reticulocytes circulate for about 1 day; therefore, the normal reticulocyte count is 0.4%–2.9%.
    • In the setting of anemia from blood loss, the BM should increase its production of RBCs in response to the blood loss, and thus a reticulocyte count of 1% in this setting is inappropriately low.
    • The reticulocyte index (RI) is a determination of the BM’s ability to respond to anemia and is calculated by % reticulocytes/maturation correction × actual Hct/normal Hct (normally 45). The maturation correction factor is 1.0 for Hct > 30%, 1.5 for 24%–30%, 2.0 for 20%–24%, and 2.5 for <20%. RI <2 with anemia indicates decreased production of RBCs (hypoproliferative anemia). RI >2 with anemia may indicate a compensatory increase in RBC production caused by hemolysis or bleeding (hyperproliferative anemia).
    • The absolute reticulocyte count (relative reticulocyte count × RBCs) may provide a more accurate reflection of a patient’s response to anemia than the relative reticulocyte count.
  • The peripheral smear should be reviewed to assess the morphologic characteristics of RBCs including the shape, size, presence of inclusions, and orientation of cells in relation to each other. RBCs assume many abnormal forms, such as acanthocytes, schistocytes, spherocytes, or tear drop cells, and abnormal orientation such as agglutination or rouleaux formation. Each is associated with several specific disease processes that may warrant additional evaluation.

Diagnostic Procedures

A BM biopsy may be indicated in cases of unexplained anemia with a low reticulocyte count or with anemia associated with other cytopenias. The severity of anemia that should trigger a BM biopsy is not well defined, but it should be strongly considered if the diagnosis is uncertain and RBC transfusions are required.

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