Anemia of chronic disease laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Laboratory Findings
Mild normocytic and normochromic anemia
Hemoglobin concentration of 10 to 11 g/dL.
Microcytic and hypochromic in less than 25 percent of the cases with a mean corpuscular volume (MCV) is rarely less than 70 fL [2,10}
The mean corpuscular hemoglobin (MHC) is normal or low similar to the MCV, and the red cell distribution width (RDW) is normal to increased.
No significant changes in the mean corpuscular hemoglobin concentration (MCHC).
Severe anemia, with a hemoglobin concentration <8 g/dL, occurs in approximately 20 percent of cases. The absolute reticulocyte count is frequently low (<25,000/microL)
Elevation in cytokines (eg, IL-6, interferon-gamma) as well as acute phase reactants (eg, fibrinogen, erythrocyte sedimentation rate, C-reactive protein, ferritin, haptoglobin, factor VIII) [81,82].
Iron studies — The serum iron concentration and transferrin level (also measured as total iron binding capacity, TIBC) are both low and the percent saturation of transferrin (TSAT) is usually normal or low-normal. The latter two findings help to distinguish ACD from iron deficiency anemia, in which the transferrin level is increased and TSAT is low (table 1).
However, approximately 20 percent of patients with ACD have a TSAT in the iron deficiency range (as low as 10 percent). In most patients, the effect of hepcidin to block the release of iron from macrophages is responsible for the low serum iron levels and low TSAT (figure 2 and figure 4). (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Iron studies (list of available tests)'.)
The serum ferritin concentration, which is usually normal or elevated in ACD, is a poor index of iron stores in chronic inflammatory diseases since ferritin is also an acute phase reactant (table 2). In addition, the destruction of hepatic or splenic tissue due to the primary disease may release relatively large amounts of ferritin into the circulation. (See "Acute phase reactants" and "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Patients with inconclusive initial testing or comorbidities'.)
Soluble transferrin receptor — Measurement of the soluble transferrin receptor (sTfR; also called circulating transferrin receptor or serum transferrin receptor) provides a quantitative measure of total erythropoietic activity, since its concentration in serum is directly proportional to the erythropoietic rate and inversely proportional to tissue iron availability. Accordingly, sTfR is normal in patients with ACD, while it is increased in those with iron deficiency anemia (IDA). This subject is discussed in depth separately. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Diagnostic evaluation'.)
The biologic principle is that in iron deficiency states, cellular membrane transferrin receptor density increases, with the result that truncated forms of sTfR appear in the serum in increased amounts. Measurement of sTfR can distinguish between IDA and ACD [83-86].
sTfR - ferritin index — Calculation of the ratio of sTfR (expressed as mg/L) to ferritin (expressed as mcg/L), or the ratio of sTfR to the logarithm (to the base 10) of the ferritin concentration may also be useful for distinguishing between ACD and IDA (figure 5). (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Diagnostic evaluation'.)
This ratio is effective in making this distinction since the numerator (sTfR) is increased in IDA and normal in ACD, while the denominator (ferritin or log ferritin) is decreased in IDA and normal to increased in ACD. Specifically, a sTfR/log ferritin ratio (TfR-ferritin index) <1 suggests the diagnosis of ACD, while a ratio >2 suggests the presence of IDA [10,87]. Those with the combination of IDA and ACD will also have a TfR-ferritin index >2.
Peripheral blood smear — The red cells in patients with ACD are normocytic and normochromic in over 75 percent of cases. Stigmata of the underlying disorder may be present on the peripheral smear, such as leukocytosis with a "left shift" in infection, the presence of leukemic or malignant cells, or leukopenia/lymphocytopenia in those with cancer or acute or chronic disorders involving the immune system. (See "Approach to the patient with neutrophilia" and "Evaluation of the peripheral blood smear", section on 'Worrisome findings' and "Approach to the child with lymphocytosis or lymphocytopenia", section on 'Lymphocytopenia'.)
Bone marrow studies — Examination of the bone marrow for its content and distribution of iron is instructive, although this examination is not performed routinely in patients with suspected ACD. In the most classical presentation of ACD, bone marrow macrophages contain normal or increased amounts of storage iron, reflecting reduced export of iron from macrophages due to the action of hepcidin. In addition, erythroid precursors show decreased or absent staining for iron (ie, decreased numbers of sideroblasts), reflecting reduced availability of iron for red cell production (picture 1) [88].
References
- ↑ Gangat N, Wolanskyj AP (July 2013). "Anemia of chronic disease". Semin. Hematol. 50 (3): 232–8. doi:10.1053/j.seminhematol.2013.06.006. PMID 23953340.
- ↑ Weiss G, Goodnough LT (March 2005). "Anemia of chronic disease". N. Engl. J. Med. 352 (10): 1011–23. doi:10.1056/NEJMra041809. PMID 15758012.
- ↑ Vreugdenhil G, Löwenberg B, van Eijk HG, Swaak AJ (1990). "Anaemia of chronic disease in rheumatoid arthritis. Raised serum interleukin-6 (IL-6) levels and effects of IL-6 and anti-IL-6 on in vitro erythropoiesis". Rheumatol. Int. 10 (3): 127–30. PMID 2392639.
- ↑ Macciò A, Madeddu C, Massa D, Mudu MC, Lusso MR, Gramignano G, Serpe R, Melis GB, Mantovani G (July 2005). "Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia". Blood. 106 (1): 362–7. doi:10.1182/blood-2005-01-0160. PMID 15774616.