Determination of Iron Metabolism-related Reference Values in a Healthy Adult Population

Abstract

Although iron evaluation on bone marrow aspirates remains the gold standard for assessing iron status, several other methods have been implemented that are less invasive and more practical. Serum iron, percentage of saturation, and total iron-binding capacity, however, lack sensitivity and are too labile to be of value as single determiners (1). Indirect measures of the functional iron compartment, such as mean cell volume and red cell distribution width, have the disadvantage of becoming indicators relatively late in the development of iron deficiency (2). Serum ferritin can be used as a marker of the iron storage compartment because it is the earliest marker to decrease with iron depletion. However, because ferritin is an acute-phase reactant in serum, its concentration may rise disproportionately to the iron storage status during inflammation, infection, or neoplasia (3), an occurrence that limits utility of ferritin in the differential diagnosis between anemia from iron deficiency and anemia from chronic disease (4). Because the soluble transferrin receptor (sTfR) concentration is not influenced by acute-phase reactions, it remains within reference values in patients with anemia of chronic disease. sTfR, therefore, can be used as a more reliable index of iron deficiency anemia (5)(6). The correlation between sTfR and bone marrow erythropoetic activity allows the use of sTfR for monitoring erythropoetin therapy, with sTfR increasing 4 weeks before the first increase of hemoglobin (7). However, conditions associated with erythroid hyperplasia can also lead to an increase of sTfR in the absence of iron deficiency (8). The sTfR/log ferritin ratio (sTfR/ferritin ratio) is reported to be even more sensitive in the presence of borderline normal ferritin and/or sTfR concentrations. This index may also be useful in distinguishing iron deficiency from conditions with hyperplastic erythropoiesis (2). Because of the lack of international standardization, different reference values for sTfR …