The usual signals of iron deficiency are a decreased MCV (or anemia with a low-normal MCV) or elevated RDW. Hypochromia with or without microcytosis on peripheral blood smear is also suspicious. Conditions frequently associated with chronic iron deficiency (e.g., malabsorption, megaloblastic anemia, pregnancy, infants on prolonged milk feeding) should also prompt further investigation. The major conditions to be considered are chronic iron deficiency, thalassemia minor, and anemia of chronic disease. The most frequently used differential tests are the serum iron plus TIBC (considered as one test) and the serum ferritin. Although the serum ferritin test alone may be diagnostic, the test combination is frequently ordered together to save time (since the results of the serum ferritin test may not be conclusive), to help interpret the values obtained, and to provide additional information. Low serum iron levels plus low TIBC suggests chronic disease effect (Table 3-2 and Table 37-2). Low serum iron levels with high-normal or elevated TIBC suggest possible iron deficiency. If the serum iron level and %TS are both low, it is strong evidence against thalassemia minor. Laboratory tests for thalassemia minor are discussed elsewhere in more detail. If the serum ferritin level is low, this is diagnostic of chronic iron deficiency and excludes both thalassemia and anemia of chronic disease, unless they are coexisting with iron deficiency or the ferritin result was a lab error. If iron deficiency is superimposed on another condition, the iron deficiency can be treated first and the other condition diagnosed later. In some cases there may be a question whether chronic iron deficiency is being obscured by chronic disease elevation of the serum ferritin value. In some of these instances there may be indication for a bone marrow aspiration or a therapeutic trial of oral iron.

Since RBC indices and peripheral blood smear may appear to be normal in some patients with chronic iron deficiency, it may be rational and justifiable to perform a biochemical screening test for iron deficiency (serum iron or serum ferritin) in patients with normocytic-normochromic anemia. In fact, no single biochemical test, not even serum ferritin determination, will rule out iron deficiency simply because the test result is normal. In 42 of our patients with chronic iron deficiency anemia, 9% had an MCV of 90-100 fL and 45% overall had a normal MCV. Fifteen percent had normal serum iron levels and 65% had normal TIBC. Ten percent had a serum iron level and TIBC pattern suggestive of anemia of chronic disease (presumably coexistent with the iron deficiency). Thirty percent had a serum ferritin level greater than 15 ng/100 ml (although all but one were less than 25 ng).