Anemia is defined as a reduction in the RBC mass as measured by either the hematocrit or the hemoglobin concentration.

If severe enough, all anemias result in symptoms of tissue hypoxia (i.e., the consequence of a low oxygen-carrying capacity of the blood) including weakness, headache, feeling “cold,” and exertional dyspnea.

Acquired anemia is a symptom and not a disease. Complete investigation for the underlying pathology is imperative.

When anemia is detected, the first step in evaluation is always to exclude acute blood loss by history and physical examination, including stool guaiac for occult blood loss.

The size of the red cells, or mean corpuscular volume (MCV), is an important tool to help determine the cause of the anemia.

The corrected reticulocyte count is a useful test because it serves to divide anemias into two major categories:

A peripheral blood smear (PBS) should be ordered on all patients as part of the initial anemia evaluation.

Common lab findings that suggest the presence of a hemolytic anemia include: indirect hyperbilirubinemia, reticulocytosis, hemoglobinemia, low haptoglobin levels, and possibly hemoglobinuria.

The two broad categories of immune hemolytic anemias include the autoimmune-mediated diseases [IgM-mediated (“cold agglutinin”), IgG-mediated (“warm agglutinin”)], and drug-induced hemolytic anemia.

A positive direct Coombs’ test identifies antibodies present on a patient’s circulating red blood cells, and an indirect Coombs’ test identifies antibodies present in a patient’s serum capable of reacting with red blood cells.

The presence of hypersegmented neutrophils on PBS in the setting of a macrocytic anemia indicates the presence of a megaloblastic process, that is, vitamin B₁₂ or folate deficiency and can help to differentiate the megaloblastic macrocytic anemias from other macrocytic processes.

Vitamin B₁₂ deficiency generally takes years to develop since the body maintains a storage pool in the liver; folate deficiency, however, can develop over weeks to months.