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Letter to the Editor |
Address correspondence to Jong Weon Choi, M.D., Ph.D., Department of Laboratory Medicine, Inha University Hospital, 7-206, 3-ga, Shinheung-dong, Jung-gu, Incheon, 400-711, South Korea; tel 82 32 890 2503; fax 82 32 890 2529; e-mail jwchoi{at}inha.ac.kr.
To the Editor
Patients who have a chronic inflammatory disorder persisting more than 1 month usually develop mild or moderate anemia. Differentiation of the type of anemia is important in planning therapeutic modalities. Discriminating between iron deficiency anemia and anemia of chronic diseases is difficult, especially when the anemia is mild, because the changes in results of iron-related tests are of small magnitude. Several investigators reported that the lower limit of serum ferritin for iron depletion in patients with chronic diseases is variously 45 µg/L [1], 50 µg/L [2], or 60 µg/L [3].
Serum ferritin is influenced by many conditions, but serum soluble transferrin receptor (sTfR) is not affected by inflammatory states. Bessman et al [4] proposed a system of classifying anemias based on red cell distribution width (RDW). Few studies have examined the ability of sTfR in conjunction with RDW to identify anemia.This study investigated the usefulness of a combination index (sTfR and RDW) for the assessment of anemia in patients with chronic diseases.
A total of 72 anemic subjects with chronic disorders (25 men and 47 women; ages 32 to 61 yr) were investigated by measurements of serum sTfR concentrations, blood hemogram, corpuscular indices, and serum iron profiles. The subjects comprised patients with tuberculosis (n = 15), rheumatoid arthritis (n = 45), pyelonephritis (n = 4), and osteoarthritis (n = 8). Patients showing a decreased hemoglobin level (<13 g/dl in men; <12 g/dl in women) were considered to have anemia.The diagnostic cutoff value of sTfR for iron deficiency was defined as 3.31 mg/L, which was based on the reference interval of sTfR in healthy adults [5]. The lower limit of serum iron level (<50 µg/dl) and the upper limit of RDW (>14.5%) were determined on the basis of reference ranges in our laboratory (95% confidence intervals). Subjects were categorized in 2 groups: (a) serum iron <50 µg/dl and sTfR >3.31 mg/L (n = 24); and (b) RDW >14.5% and sTfR >3.31 mg/L (n = 21).
After the subjects had fasted, venous blood was drawn in evacuated tubes. Serum sTfR levels were measured by an immunoenzymetric method (IDeA sTfR kit, Orion Diagnostica, Espoo, Finland). Complete blood cell count and red cell indices were measured with an electronic counter (SE 9000; Sysmex, Kobe, Japan). Serum iron and total iron-binding capacity were assayed with a chemical analyzer (Hitachi 7600; Hitachi, Tokyo, Japan), and serum ferritin was measured by a chemiluminescent method (ACS 180; Bayer Diagnostics, Tarrytown, NY, USA).
Wilcoxon’s rank sum test was used to compare laboratory data of each group because of the small subject number. Correlation coefficients were analyzed by Spearman’s method. All p values <0.05 were considered significant.
Among the hematologic variables, RDW most accurately reflected sTfR concentrations in patients with chronic diseases (r = 0.62, p <0.05). These data are in partial agreement with the results of a previous study, which demonstrated that sTfR concentrations correlated more strongly with corpuscular indices than with iron parameters in both iron-deficient subjects and healthy individuals [6]. These observations are presumably attributable to the feature of sTfR representing erythropoietic activities.
In this study, we tested whether the ability of the combination of sTfR and RDW for evaluating anemia is comparable to a well-known parameter, ie, the combination of sTfR and serum iron. As shown in Table 1
, subjects with RDW >14.5% and sTfR >3.31 mg/L exhibited significantly lower hemoglobin levels than those with serum iron <50 µg/dl and sTfR > 3.31 mg/L (8.2 ± 1.1 vs 9.4 ± 1.2 g/dl, p < 0.05). There were no significant differences in iron parameters and corpuscular indices between the 2 groups.
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In the present study, we also evaluated the efficiency of the lower limit of ferritin, which some researchers propose as a sensitive indicator for iron depletion in patients with chronic diseases. At a diagnostic cutoff of iron deficiency (sTfR >3.31 mg/l and serum iron <50 µg/L), the positive predictive values of ferritin of 45 µg/L, 50 µg/L, and 60 µg/L were 35.3%, 37.1%, and 34.2%, respectively (Table 2). These results suggest that diagnostic efficacy of serum ferritin is low and that changing the elevated ferritin cut-off level from 45 µg/L to 60 µg/L does not improve its predictive value in the detection of iron deficiency.
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In conclusion, the present study describes how the combination of sTfR with RDW will be useful in diagnosis of iron deficiency, especially for anemic patients with chronic diseases, in whom routine tests of iron status are compromised by various factors such as inflammation and medications.
References
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