Chapter 13: Anemia of Chronic Inflammation

• 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.

• 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).

• 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.

• 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.