Biology Reference
In-Depth Information
Diagnosis
The diagnosis of ACD is typically made by the demonstration of anemia with
inappropriately low reticulocyte counts with a low serum or plasma iron con-
centration despite adequate reticuloendothelial iron stores. Although it is most
commonly seen in patients with a concurrent infectious, inflammatory, or neo-
plastic syndrome, in one series 40% of ACD patients lacked a traditional
chronic disease [3]. This finding is a consequence of the cytokine-mediated
basis of this syndrome.
The decreased serum iron concentration may lead to confusion between
ACD and iron-deficiency anemia. Although typically a normocytic anemia,
20% to 50% of patients with ACD will have decreased erythrocyte mean cor-
puscular volume (MCV) [3, 4]. Serum total iron-binding capacity and/or trans-
ferrin concentration is traditionally said to be increased in iron deficiency and
normal or decreased in ACD; however, in a recent multicenter study involving
patients with complicated medical histories, only one of 24 patients with
absent marrow iron stores had an increased serum total iron-binding capacity
[14]. Although the serum ferritin concentration is the single best biochemical
indicator of reticuloendothelial iron status, it has limited sensitivity in patients
with concurrent inflammatory disorders. Serum ferritin is frequently increased
disproportionately to iron stores. In a single-institution study correlating mar-
row iron stores to biochemical iron parameters, approximately 50% of patients
without stainable marrow iron had serum ferritin concentrations in the normal
range; a third of these iron-deficient patients had serum ferritin concentrations
>100 g/L [15].
The determination of serum soluble transferrin-receptor concentration
(TfR) appears to provide a solution to the problem of distinguishing iron defi-
ciency with inflammation from ACD. TfR are predominantly expressed on
erythroblasts; iron-deficiency erythroblasts express an increased number of
TfR/cell [16], while those from patients with ACD express fewer TfR [17]. In
addition, iron-deficient individuals often exhibit marrow erythroid hyperpla-
sia, resulting in a further increment in cellular TfR numbers. Since the serum
TfR concentration reflects the total body quantity of erythroblast cellular TfR
[18], it would be predicted that this test could effectively distinguish iron defi-
ciency and ACD; and initial reports supported this prediction [19]. More recent
studies (using a different TfR assay), however, suggest that this picture is
somewhat more complicated. A significantly increased proportion of increased
TfR concentrations was noted in individuals with serum ferritin concentrations
well above the upper limits of the normal range in one study of 77 patients
[15]. The same phenomenon was observed in a larger study prospectively cor-
relating marrow aspirate iron stores to serum TfR concentrations in 145
patients with anemia [14]. The authors proposed an algorithm in which
patients with serum ferritin concentrations below the normal range were pre-
dicted to lack stainable marrow iron, patients with serum ferritin concentra-
tions outside the normal range were predicted to be iron replete; and patients
