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

Abstract

Background: 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. Methods: 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. Results: 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 ≤20.8 μg/L and >1.5, respectively. Corresponding values in patients with APR were ≤61.7 μg/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. Conclusion: 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.

A prospective observational study of anaemia management in cancer patients - results from the German Cancer Anaemia Registry

“…This might be due to the lack of reliable laboratory predictors of treatment response to ESA (Steinmetz et al 2007) and the corresponding lack of specific recommendations on diagnostic measures in practice guidelines. However, in the recent TANDEM study, we were not only able to confirm the value of intravenous iron supplementation to improve response to ESA, but, based on the diagnostic plot (Thomas & Thomas 2002), also to identify within anaemic cancer patients scheduled for ESA treatment subgroups that were only iron deficient (Steinmetz et al 2010). Such novel diagnostic approaches as well as the underuse of already available diagnostics in common practice need to be addressed in future revisions of treatment guidelines.…”

Anaemia in the critically ill patient: monitoring of erythropoietin therapy

“…As an indicator for proliferation and iron availability to the bone marrow, the ratio of serum soluble transferrin receptor (sTfR) concentration to the logarithm of serum ferritin concentration (sTfR/log ferritin = ferritin index) is a valuable tool [9]. In healthy subjects, Ret-Hb is 28-35 pg and the ferritin index is < 1.5 [10]. In critically ill patients with elevated C-reactive protein (CRP), the threshold for the ferritin index indicating hypoproliferative erythropoiesis and normal iron availability to the marrow is ≤ 0.8.…”

“…In critically ill patients with elevated C-reactive protein (CRP), the threshold for the ferritin index indicating hypoproliferative erythropoiesis and normal iron availability to the marrow is ≤ 0.8. More recently Thomas and Thomas [10] developed a diagnostic plot combining Ret-Hb and the ferritin index, which allows the identification of four major erythropoietic states ( Fig. 1): 1.…”

“…Ferritin index thresholds for the Dade-Behring sTfR assay are shown. From[10]. Therapeutic implications for treating different phases of iron deficiency.…”

“…Therapeutic implications for treating different phases of iron deficiency. From[10].E M I A I N T H E C R I T I C A L L Y I L L P A T I E N T © 2 0 0 6 T H E A U T H O R S J O U R N A L C O M P I L A T I O N © 2 0 0 6 B J U I N T E R N A T I O N A L 11 6 3…”