Potential Utility of Ret-Y in the Diagnosis of Iron-Restricted Erythropoiesis

Abstract

Diagnosis of iron deficiency (ID) or functional iron deficiency (FID) is particularly challenging in patients with acute or chronic inflammatory conditions because most biochemical markers for iron metabolism are affected by the acute-phase response (APR) (1). The hemoglobin content of reticulocytes (CHr) is an early and sensitive indicator of FID (2). Recently, we presented a novel approach to provide insights into the diagnosis of FID in APR by use of the CHr (3). ID and FID were defined as a CHr <28 pg based on the distribution of CHr and biochemical markers of iron status in healthy controls. When a CHr <28 pg was used for identification of ID and FID in anemic patients, the values of ferritin, soluble transferrin receptor (sTfR), and the sTfR-F index (sTfR/log ferritin) (4) performed significantly better in patients without APR [based on a C-reactive protein (CRP) cutoff of 5 mg/L]. In ID combined with inflammation, the cutoff value for the sTfR-F index was 0.8, and in simple ID, it was 1.5. A diagnostic plot was developed that combined CHr and sTfR-F index, which allowed identification of four major categories of ID: ( a ) iron repletion, normal erythropoiesis; ( b ) patients with reduced iron supply, but not yet in an iron-deficient erythropoietic state; ( c ) depletion of storage and functional iron with decreased hemoglobinization of erythrocytes, classic ID; and ( d ) FID in an iron-replete state, with decreased hemoglobinization of erythrocytes. The plot provided a useful approach to the diagnosis of iron-deficient states. To date, the measurement of reticulocyte hemoglobin has been restricted to the analyzers of a single manufacturer. Now a second manufacturer has produced what would appear to …