Anemia, Chronic Disease



  • Otherwise known as anemia of chronic inflammation
  • During chronic systemic infection, inflammation, or malignancy, the production of proinflammatory mediators causes inhibition of erythropoiesis as well as the imbalance in iron homeostasis (1).
  • Anemia of chronic disease (ACD) is characterized as a normocytic, normochromic, hypoproliferative anemia and classically has low serum iron levels, elevated ferritin levels, and elevated total iron-binding capacity (TIBC) (1),(2).
  • Anemia is typically mild to moderate with hemoglobin (Hgb) rarely <8 g/dL.


There is limited data on the incidence of ACD.

ACD is the second most common anemia after iron deficiency anemia (IDA) due to the aging population and the high prevalence of chronic infections and inflammatory disorders in the United States. Overall, the estimated worldwide prevalence of undifferentiated anemia is 24.8% (3).

Etiology and Pathophysiology

  • Production of red blood cells is decreased as a result of functional iron deficiency.
  • In general, the severity of the anemia will correspond with the severity of the underlying disease (1).
  • Proinflammatory cytokines such as interleukins (IL), tumor necrosis factor (TNF), bone morphogenic proteins (BMP), and interferons (IFN) create changes in iron homeostasis in several ways (1):
    • Dysregulating iron homeostasis
    • Diminishing proliferation as well as differentiation of red blood cell progenitor cells
    • Blunting the erythropoietic response
    • Increasing erythrocyte phagocytosis and apoptosis
  • Iron overload and the proinflammatory cytokines IL-1, IL-6, and BMP6 increase the production of the iron-regulating hormone hepcidin in hepatocytes, macrophages, and enterocytes (1).
    • Hepcidin binds to ferroportin causing internalization and degradation, preventing efflux of iron from stores in macrophages and hepatocytes, stopping iron absorption by duodenal enterocytes.
      • This results in low serum iron levels and inhibited erythropoiesis known as iron-restricted erythropoiesis.
    • As a result, iron delivery to erythroid progenitor cells within bone marrow is reduced and erythropoiesis is diminished, causing anemia.
  • Erythropoietin (EPO) production and the response to EPO by erythroid bone marrow is suppressed by proinflammatory cytokines such as IL-1, TNF-α, and IFN-γ (1).
  • Inflammatory cytokines may also cause erythrophagocytosis and oxidative damage, reducing RBC survival.

Risk Factors

Risk factors for anemia of chronic disease include hepatic disease, renal disease, and other infections or autoimmune causes of the commonly associated conditions below.

General Prevention

Prevention of anemia of chronic disease involves timely and undergoing treatment of the associated conditions below.

Commonly Associated Conditions

  • Chronic systemic diseases
    • Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, temporal arteritis, inflammatory bowel disease (IBD), systemic inflammatory response syndrome (SIRS)
  • Hepatic disease or failure
  • Congestive heart failure or coronary artery disease
  • Chronic kidney disease (CKD)
  • Acute or chronic infections
    • Viral
      • HIV, HCV
    • Bacterial
      • Abscess, subacute bacterial endocarditis, tuberculosis, osteomyelitis
    • Fungal
    • Parasitic
  • Malignancies
  • Cytokine dysregulation (anemia of aging)
  • Hypometabolic states
    • Protein malnutrition, thyroid disease, panhypopituitarism, diabetes mellitus, Addison disease

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