Laboratory Diagnosis of Iron Deficiency

Until about 20 years ago, the diagnosis of iron deficiency was justifiably considered a simple matter. The focus of attention was then on hospitalized patients with a severe or moderate degree of anemia. When iron deficiency was suspected, the diagnosis could be substantiated by a decrease in serum iron, an elevation in the total iron-binding capacity (TIBC), and the typical changes of microcytosis, anisocytosis, and hypochromia on the blood smear. After the initiation of iron treatment, a rise in the reticulocyte count after 1 to 2 weeks and a slower, more gradual correction of the hemoglobin or hematocrit after about 2 months would confirm the diagnosis. During the last 20 years, however, attention has shifted to the more common, milder cases of iron deficiency that are typically seen in an outpatient setting. Mild cases, in which the concentration of hemoglobin may be no more than 1 g/dl below the reference range, have proven to be an unexpectedly difficult diagnostic challenge. This is partly because textbook recommendations for diagnosis are often based on severe iron deficiency anemia and cannot be successfully extrapolated to the mild cases. The two types of patients require different diagnostic approaches. In mild iron deficiency, the initial laboratory tests are less reliable in predicting a hemoglobin response than with severe iron deficiency because there is a substantial overlapping of results between iron-deficient and iron-sufficient populations (1-3). In contrast to severe iron deficiency, the blood smear cannot be distinguished from that of a normal individual (4). Furthermore, after treatment is initiated, the reticulocyte count does not usually rise sufficiently to allow a response to be detected. In partial compensation for these inherent difficulties in diagnosing mild iron deficiency, there have been many technical improvements in established laboratory tests and a broader application of additional laboratory tests (5,6). Laboratory tests that have come into widespread use include the mean corpuscular volume (MCV), erythrocyte protoporphyrin (EP), and serum ferritin. Progress has also been made in automating and standardizing each of these laboratory tests as well as serum iron, TIBC, and hemoglobin analysis. The availability of more reproducible methods has led to increasingly reliable normative data for age and sex which are based on