• Associated with infections, collagen vascular diseases, inflammatory diseases, and malignancies.
• Shortened red-cell survival due to extracellular destructive process. Possible enhanced phagocytic activity of macrophages.
• Impaired bone marrow erythropoietic response to the anemia with a blunted increase in red-cell production of only once to twice normal. Decreased marrow response to erythropoietin.
• Impaired erythroid progenitor response.
• Impaired mobilization of reticuloendothelial system iron stores.
• Suppression of erythropoiesis by one or more of the inflammatory cytokines such as IL-1, g-IFN, and TNF-a.

• Main differential is iron deficiency anemia.
• In both iron deficiency and anemia of chronic diseases
  • Decreased plasma iron
  • transferrin saturation
  • marrow sideroblasts
  • elevated free erythrocyte protoporphyrin (FEP)
  • low reticulocyte count.
• In anemia of chronic disease
  • low iron-binding capacity
  • normal or elevated reticuloendothelial iron
  • normal serum ferritin
  • increased hemosiderin within the macrophages
• In iron deficiency
  • high iron-binding capacity
  • low reticuloendothelial iron
  • low serum ferritin.

• Underlying disease process exists. Disease entities often associated with anemia of chronic disease include infections, both acute and chronic; inflammatory disease; collagen vascular diseases; malignancies, and renal failure.
• The anemia develops over the first month of the disease process and then remains fairly stable over time.

Finding: Mild pallor.
Significance: Because the onset of anemia of chronic disease is insidious and the level of anemia tends to stabilize, the degree of pallor is mild.

Finding: No signs of circulatory compromise.
Significance: Increased cardiac output to compensate for anemia.

• Complete blood count with indices: Normocytic, normochromic (can be microcytic, hypochromic) anemia with hematocrit rarely less than 20%
• Reticulocyte count: Usually in the normal range, but low for the level of anemia.
• Iron studies: Low plasma iron, with low total iron-binding capacity, low transferrin saturation by iron, normal or high ferritin, elevated FEP.
• Hemosiderin in bone marrow macrophages is increased if bone marrow aspiration is done and the aspirate is viewed with iron stains. This is generally not indicated.
• Albumin and transferrin: Both low.
• Acute-phase reactants like C-reactive protein may be elevated.

• If only the serum iron is obtained without the remainder of iron studies, the child may be inappropriately diagnosed with iron deficiency.
• Anemia of chronic disease often coexists with other causes of anemia, including: occult blood loss, dietary iron deficiency and drug-related marrow suppression.

• Iron: There is no role for iron therapy unless the is coexisting iron-deficiency anemia.
• Recombinant human erythropoietin: Effective, but indications for use are still not universally accepted. Clearly utilized in chronic renal failure. Should be used for more severe and symptomatic anemia where the underlying disease is likely to be prolonged and difficult to treat. Should be used in patients who are otherwise transfusion-dependent. Often used in childhood cancer to decrease the exposure to blood products.

• Treatment should be directed at the underlying disease process.
• Transfusion of packed red blood cells is sometimes indicated intermittently in severe anemia with hemodynamic compromise.

• Treatment of underlying disease process may promote slow resolution of associated anemia.
• Hematocrit increase about 6-8 weeks after start of recombinant human erythropoietin therapy. Continues to rise over 6 months.

Q: Does anemia that is associated with a chronic disease require further evaluation?
A: If the anemia fits within the general guidelines of diagnosis as outlined above, there is no need to pursue further investigation, except in specific cases. If there is an associated malignancy where marrow metastasis is possible, a bone marrow aspirate and biopsy should be done. In conditions with malabsorption, nutritional deficiencies and blood loss should be ruled out.

Bertero MT, Caligaris-Cappio F. Anemia of chronic disorders in systemic autoimmune diseases. Haematologica 1997;82:375–381.

Means RT. Clinical application of recombinant erythropoietin in the anemia of chronic disease. Hematol Oncol Clin North Am 1994;8:933–944.

Mean RT. Erythropoietin in the treatment of anemia in chronic infectious, inflammatory, and malignant disease. Curr Opin Hematol 1995;2:210–213.

Shine JW. Microcytic anemia. Am Fam Phys 1997;55:2455–2462.