A Differential Diagnosis of Microcytic Hypochromic Anemia for High‐Risk Patients

Abstract

To the Editor: Traditionally, the differential diagnosis of microcytic hypochromic anemia includes, among others, iron deficiency anemia (IDA), anemia of chronic disorders (ACD), thalassemia, and sideroblastic anemia.1 The coexistence of hyperferritinemia should, in theory, be the feature that distinguishes IDA from other subtypes of microcytic hypochromic anemia; but in practice, IDA may coexist with chronic inflammatory disorders, with the consequence that serum ferritin levels up to 100 ng/mL may be compatible with unrecognized IDA, the likelihood ratio for IDA being of the order of 0.54 in subjects with serum ferritin of 45 to 100 ng/mL and only 0.08 in patients with serum ferritin of 100 ng/mL or more.2 Consequently, it has been suggested that “a pragmatic approach to interpreting ferritin concentrations is that … levels >100 mcg/L (i.e., 100 ng/mL) rule it (iron deficiency) out”3 and that “a ferritin cut-off of 100 ng/mL can be used to determine the need for colonoscopy in men with anemia.”4 Neither of these proposals3, 4 takes cognizance of the fact that prolonged chronic inflammation attributable to an unrecognized cause of chronic blood loss can generate high levels of serum ferritin despite depletion of iron stores. Anemia of the microcytic or hypochromic subtype may be the sole manifestation of a disorder for a long time, which then generates normal or even high levels of ferritin in the face of iron deficiency. The clue to recognition of the underlying cause is to include IDA in the differential diagnosis of the association between microcytic hypochromic anemia and normal or even high levels of serum ferritin. This was the case in a study in which serum ferritin levels up to 480 ng/mL were documented in 50 patients with histologically proven colorectal cancer.5 In another study, in which the original intention was to submit to gastroenterological investigation only patients in whom anemia of the microcytic or hypochromic subtype was associated with serum ferritin levels less than 100 ng/mL, in 17 cases of right-sided colonic neoplasm, three were identified with serum ferritin levels of 160 ng/mL, 142 ng/mL, and 356 ng/mL. The latter two instances were associated with palpable cecal neoplasms.6 Accordingly, when using microcytic or hypochromic anemia as a screening tool for occult blood loss attributable to colorectal carcinoma,7 right-sided colonic carcinoma should be included in the differential diagnosis of the association between microcytic or hypochromic anemia and normal or even high levels of serum ferritin. Microcytic or hypochromic anemia is more prevalent when colonic carcinoma is right sided than when it is more distal,7 and it is in the former context in which chronic blood loss goes along with chronic inflammation during the prolonged asymptomatic phase of this disorder. These caveats are especially relevant to population subgroups such as elderly people, in whom the risk of colorectal carcinoma is high, not only when its manifestations are easily recognizable,8 but also when it has a prolonged asymptomatic phase.9 Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this letter. Author Contributions: Author is the sole contributor to this letter. Sponsor's Role: None.