Biochemical Markers and Hematologic Indices in the Diagnosis of Functional Iron Deficiency

TLDR

The hypochromic red cell directly indicates functional iron deficiency, unlike most biochemical markers that only indirectly reflect iron‑deficient erythropoiesis. This study aimed to assess how biochemical markers differentiate functional iron deficiency from anemia of chronic disease and their combined state, using red‑cell hemoglobinization as the gold standard in 442 anemic and 154 nonanemic patients. Researchers measured reticulocyte hemoglobin content and hypochromic red‑cell proportion with an Advia 120 analyzer, alongside ferritin, transferrin, transferrin saturation, soluble transferrin receptor, and the sTfR/log‑ferritin ratio, applying defined thresholds to identify iron‑deficient erythropoiesis in patients with and without acute‑phase response. Positive likelihood ratios ranged from 2.6 to 6.9 for biochemical markers and 4.3 to 16.5 for the sTfR‑F index, yet biochemical markers were less reliable in acute‑phase response patients, while diagnostic plots of sTfR‑F versus.

Abstract

The hypochromic red cell is a direct indicator of functional iron deficiency (ID) in contrast to the majority of biochemical markers, which measure functional ID indirectly via iron-deficient erythropoiesis. The aim of this study was to evaluate the extent to which these biochemical markers can distinguish ID from anemia of chronic disease (ACD) as well as from the combined state of functional ID/ACD, using red cell hemoglobinization as the gold standard.We studied 442 patients with various disease-specific anemias and 154 nonanemic patients. As indicators of red cell hemoglobinization, we measured the reticulocyte hemoglobin content (CHr) and the proportion of hypochromic red cells (HYPO), using an Advia 120 hematology analyzer. Ferritin, transferrin, transferrin saturation, and the concentration of the soluble transferrin receptor (sTfR) were determined by ELISA and immunoturbidimetric assay. The sTfR/log ferritin ratio (sTfR-F index) was used as an additional marker for biochemical identification of iron-deficient erythropoiesis.In a control group (n = 71), the 2.5 percentile values were 28 pg for CHr and 5% for HYPO. These values were used to indicate unimpaired red cell hemoglobinization and absence of functional ID. In patients with deficient red cell hemoglobinization but no acute-phase response (APR), iron-deficient erythropoiesis was indicated by serum ferritin and sTfR-F index values < or =20.8 microg/L and >1.5, respectively. Corresponding values in patients with APR were < or =61.7 microg/L and >0.8, respectively. The positive likelihood ratios for the biochemical markers and the sTfR-F index for identifying iron-restricted erythropoiesis in patients with and without APR were 2.6-6.9 and 4.3-16.5, respectively.In APR patients, biochemical markers demonstrate weaknesses in the diagnosis of functional ID as defined by hematologic indices. Use of diagnostic plots to illustrate the relationship between the sTfR-F index and CHr allows the progression of ID to be identified, regardless of whether an APR is present.