Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + DEFINITION Download Section PDF Listen +++ ++ Anemia associated with chronic infection, inflammatory or neoplastic disease. Also referred to as anemia of chronic disease. One to 2 months of sustained disease is required for anemia to develop. Anemia is moderate, with a hemoglobin level between 7 and 11 g/dL, and is rarely symptomatic. The characteristic features of anemia of inflammation (AI) are listed in Table 13–1. ++Table Graphic Jump LocationTABLE 13–1LABORATORY STUDIES OF IRON METABOLISM IN IRON-DEFICIENCY ANEMIA (IDA), ANEMIA OF INFLAMMATION (AI), AND A COMBINATION OF THE TWO.View Table||Download (.pdf) TABLE 13–1 LABORATORY STUDIES OF IRON METABOLISM IN IRON-DEFICIENCY ANEMIA (IDA), ANEMIA OF INFLAMMATION (AI), AND A COMBINATION OF THE TWO. IDA (n = 48) AI (n = 58) Combination (n = 17) Hemoglobin, g/L 93 ± 16 (96) 102 ± 12 (103) 88 ± 20 (90) MCV, fL 75 ± 9 (75) 90 ± 7 (91) 78 ± 9 (79) Iron, μmol/L (10–40) 8 ± 11 (4) 10 ± 6 (9) 6 ± 3 (6) Transferrin, g/L (2.1–3.4m, 2.0–3.1f) 3.3 ± 0.4 (3.3) 1.9 ± 0.5 (1.8) 2.6 ± 0.6 (2.4) Transferrin saturation, % 12 ± 17 (5.7) 23 ± 13 (21) 12 ± 7 (8) Ferritin, μg/L (15–306m, 5–103f) 21 ± 55 (11) 342 ± 385 (195) 87 ± 167 (23) TfR, mg/L (0.85–3.05) 6.2 ± 3.5 (5.0) 1.8 ± 0.6 (1.8) 5.1 ± 2.0 (4.7) TfR/log ferritin 6.8 ± 6.5 (5.4) 0.8 ± 0.3 (0.8) 3.8 ± 1.9 (3.2) Reproduced with permission from Punnonen K, Irjala K, Rajamaki A: Blood 89:1052, 1997.Source: Williams Hematology, 8th ed, Chap. 37, Table 37–2, p. 506. + PATHOGENESIS Download Section PDF Listen +++ ++ Inflammation leads to interleukin (IL)-6 production, which induces hepatocyte hepcidin production, which blocks intestinal iron absorption and iron release from macrophages and hepatocytes. Hepcidin binds to and leads to feroportin degradation, the primary cell surface iron exporter. Impaired intestinal iron uptake and impaired release of iron from macrophages leads to a low level of serum iron and consequent low saturation of transferrin. Enhanced activity of macrophages increases erythrocyte destruction. Production of erythropoietin (EPO) is decreased in response to anemia, and the ability of erythroid precursors to respond to EPO is impaired, both also related to inflammatory cytokine production (IL-1, tumor necrosis factor, interferons). + CLINICAL AND LABORATORY FEATURES Download Section PDF Listen +++ ++ Anemia is usually overshadowed by symptoms of the primary disease. Common conditions leading to AI are shown in Table 13–2. Low reticulocyte index for the degree of anemia. Diagnosis, especially differentiation from iron-deficiency anemia (IDA), depends on laboratory findings (see Table 13–1): — Initially normochromic, normocytic anemia; hypochromic, microcytic features develop as anemia progresses. — Low serum iron level and somewhat decreased serum transferrin concentration; decreased percent saturation of transferrin. — Level of serum ferritin, an acute phase protein, is inappropriately elevated (approximately threefold) with respect to storage iron. — Marrow contains increased storage iron. The M/E ratio is normal, and the percentage of sideroblasts is decreased. ++Table Graphic Jump LocationTABLE 13–2COMMON CONDITIONS ASSOCIATED WITH AIView Table||Download (.pdf) TABLE 13–2 COMMON CONDITIONS ASSOCIATED WITH AI Category Diseases Associated with AI Infection AIDS/HIV, tuberculosis, malaria (contributory), osteomyelitis, chronic abscesses, sepsis Inflammation Rheumatoid arthritis, other rheumatologic disorders, inflammatory bowel diseases, systemic inflammatory response syndrome Malignancy Carcinomas, myeloma, lymphomas Cytokine dysregulation Anemia of aging Source: Williams Hematology, 8th ed, Chap. 37, Table 37–1, p. 504. + DIFFERENTIAL DIAGNOSIS Download Section PDF Listen +++ ++ Drug-induced marrow suppression or drug-induced hemolysis. Iron-deficiency anemia is characterized by low serum iron, increased transferrin, decreased storage iron, decreased serum ferritin. Anemia of chronic renal failure. Myelophthisic anemia caused by carcinoma or lymphoma replacing marrow. +++ THERAPY ++ No treatment may be necessary, other than for the underlying disease. Iron (by mouth or parenterally) is contraindicated. Androgenic steroids may be of benefit but have unacceptable side effects. Packed red cell transfusions may be given, if the anemia is symptomatic. Recombinant human erythropoietin (rh-EPO) therapy is effective if serum EPO is not elevated. — Starting dose: 10,000 U of rh-EPO three times weekly or darbepoetin alfa 200 mcg every 2 weeks, subcutaneously or intravenously. — The target hemoglobin should not exceed 12 g/dL after which EPO dose should be lowered to maintain a level between 11 and 12g/dL. — If no response in 3 weeks, double dose. — If no response to higher dose in 3 more weeks, discontinue. — Hypertension and a risk of thrombotic complications with use of EPO preparations. ++ For a more detailed discussion, see Tomas Ganz: Anemia of Chronic Disease. Chap. 37, p. 503 in Williams Hematology, 8th ed.