Evaluation of Anemia

Barbara Tindle, M.D. September 2001

The term "anemia" evokes a simple definition, but finding a simple approach to the evaluation of anemia presents some challenges. The proposed guideline is an attempt to present a basic approach in a one-page scheme. Part of the algorithm indicates what tests to perform, and part indicates what disease(s) to consider. When a disease is considered, appropriate testing can be gleaned from standard hematology and clinical pathology texts. This scheme is not all-inclusive, but should serve as at least a starting point for the evaluation of anemia.

Some caveats are offered as follows:

• A CBC should initiate the evaluation.The CBC results should be no older than 48 hours from the initiation of additional testing. This is a guideline, not absolute. However, it is stated because of changing values over time eg: a CBC performed on day one may be different from that of a month later, and should be repeated if additional testing is planned for a month later.
• Red cell indices may reflect multiple etiologies, e.g. vitamin and iron deficiency. Therefore, the indices may not reflect all etiologies. Clinical information is essential in order to plan for complete/appropriate testing.

Microcytic-Hypochromic Anemia:

• Serum ferritin is a more sensitive indicator than are serum iron and iron binding capacity. Therefore, it is recommended that serum ferritin be performed first in the evaluation of microcytic-hypochromic anemia.
• Caution; serum ferritin values may not accurately reflect the true value since serum ferritin is affected in the presence of liver disease, inflammation, and bone marrow damage.
• The red blood cell count may be normal or elevated in the presence of thalassemia and other hemoglobinopathies.
• In the consideration of thalassemia, hemoglobin electrophoresis is usually recommended as the test to order. HGB A2 may be ordered together with HGEP, or may be recommended in the event that the HGEP is unclear.
• HGB A2 is elevated in thalassemia trait; but may be in the normal range if there is concomitant severe iron deficiency anemia.

Normocytic-Normochromic Anemia:

• Serum ferritin (low) will be helpful in ruling in early iron deficiency anemia when the HGB is low but the MCV is normal.
• Anemia of chronic disease (early) may be associated with normocytic-normochromic indices together with elevated serum ferritin.

Macrocytic Anemia:

• Serum folate and Vitamin B12 should be performed to evaluate for megaloblastic anemia representing deficiency of one or both vitamins.
• There is an overlap between normal and low Vitamin B12 values. If the evaluation of the patient suggests vitamin B12 deficiency, measurement of homocysteine and methylmalonic acid should be considered even if the Vitamin B12 level is within normal range.