Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD.

Maternal serum hepcidin is low at term and independent of cord blood iron status.

OBJECTIVES: Hepcidin is the key regulator of iron homeostasis. The aims of this study were to determine serum hepcidin concentrations and reference ranges in pregnant women and cord blood of newborns at term and to evaluate the associations between hepcidin concentrations and iron status parameters. METHODS: A total of 191 pregnant women-newborn pairs were studied in Kuopio University Hospital, Finland. The measured parameters were serum hepcidin, ferritin, transferrin receptor, transferrin saturation, red cell indices, and erythropoietin. RESULTS: The hepcidin concentration in pregnant women was significantly lower than in cord blood at term [geometric mean concentration (GMC) (95% confidence intervals) in pregnant women 10.7 ng/mL (8.5-13.4 ng/mL) vs. GMC of cord blood hepcidin 69.3 ng/mL (55.3-86.8 ng/mL), P<0.001, adjusted analysis of variance]. Hepcidin was undetectable in 12% of mothers. Hepcidin concentration in pregnant women was the lowest in those who had the lowest iron status. However, maternal hepcidin concentration was not associated with cord blood hepcidin or iron status markers. Hepcidin concentration in cord blood was associated with cord blood iron status, but not with maternal iron status. CONCLUSIONS: At term pregnancy, hepcidin concentrations are very low, allowing maximal availability of iron for the fetus. Maternal and cord blood hepcidin levels were independently associated with either maternal or cord blood iron status.

Transferrin receptor expression on reticulocytes as a marker of iron status in dialyzed patients.

BACKGROUND: Erythropoietin therapy should be accompanied by an adequate iron supply in order to avoid functional iron deficiency (FID) related to enhanced erythropoiesis. Therefore, accurate monitoring of the body's iron homeostasis is needed. This study was conducted to investigate whether transferrin receptor (TfR) expression on reticulocytes can reflect iron status in patients with chronic renal failure (CRF). METHODS: TfR expression [antibody binding capacity (ABC)] and the proportion of TfR positive reticulocytes (%TfR+ Ret) relative to all reticulocytes were measured by a quantitative flow cytometric method at baseline and at 3 weeks in 34 dialysis patients. Iron status (plasma ferritin and soluble TfR) and hemoglobin (Hb) with advanced cellular indices, such as the percentage of hypochromic reticulocytes (%HYPOr) and cellular Hb in reticulocytes (CHr), were also analyzed. RESULTS: Patients with FID had significantly higher TfR ABC and %TfR+ Ret compared with patients with replete iron status (p=0.034 and p=0.006, respectively). In patients whose Hb concentrations showed a reduction, the mean increase (3 weeks- baseline) in TfR ABC was four-fold higher and %TfR(+)Ret was three-fold higher when compared with patients whose Hb was stable or had increased. The changes in TfR expression correlated significantly with the changes in reticulocyte indices [CHr (negatively), %HYPOr (positively)] and plasma ferritin (negatively). CONCLUSIONS: Reticulocyte TfR expression reflected the changes in the Hb level and the iron availability at the cellular level, and therefore it might be useful in the assessment of iron status in patients with CRF.

The diagnostic accuracy of the percentage of hypochromic red blood cells (%HYPOm) and cellular hemoglobin in reticulocytes (CHr) in differentiating iron deficiency anemia and anemia of chronic diseases.

BACKGROUND: The percentages of hypochromic red blood cells (%HYPOm) and cellular hemoglobin in reticulocytes (CHr) are suggested to be useful screening markers of iron deficiency. The aim of this study was to investigate the diagnostic accuracy of %HYPOm and CHr in differentiating iron deficiency anemia (IDA) and anemia of chronic disease (ACD). METHODS: The retrospective population consisted of 58 IDA patients, 129 ACD patients and 63 controls, on whom bone marrow examination and blood count with %HYPOm and CHr had been performed. Receiver operating characteristic (ROC) analyses with area under the ROC curves (AUC) were used as statistical tests. RESULTS: AUCs for differentiating the groups using %HYPOm were as follows: IDA vs. controls 0.99, ACD vs. controls 0.85 and IDA vs. ACD 0.88. AUCs for CHr in distinguishing the groups were as follows: IDA vs. controls 0.95, ACD vs. controls 0.65 and IDA vs. ACD 0.83. CONCLUSIONS: IDA and ACD patients were efficiently differentiated by using %HYPOm and CHr. Additionally, %HYPOm was higher and CHr was lower in IDA patients and in ACD patients than in controls. Thus, %HYPOm is higher and CHr is lower not only in absolute iron deficiency, but also when iron availability for erythropoiesis is restricted.