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For further information, see CMDT Part 13-03: Anemia of Chronic Disease

Key Features

  • Many chronic systemic diseases are associated with mild or moderate anemia

  • Anemia of inflammation

    • Associated with chronic inflammatory states, such as

      • Inflammatory bowel disease

      • Rheumatoid arthritis

      • Chronic infections

      • Malignancy

    • Mediated through hepcidin (a negative regulator of ferroportin) primarily via elevated IL-6, resulting in reduced iron uptake in the gut and reduced iron transfer from macrophages to erythroid progenitor cells in the bone marrow

    • Reduced responsiveness to erythropoietin, the elaboration of hemolysins that shorten red blood cell (RBC) survival, and the production of inflammatory cytokines that dampen red cell production

    • Serum iron is low

  • Anemia of organ failure

    • Can occur with chronic kidney disease, hepatic failure, and endocrine gland failure

    • Erythropoietin is reduced and RBC mass decreases in response to a diminished signal for red blood cell production

    • Serum iron is normal (except in chronic kidney disease where it is low due to reduced hepcidin clearance and subsequent enhanced degradation of ferroportin)

  • Anemia of the elderly

    • Present in up to 20% of individuals over age 85 years and a thorough evaluation for an explanation of anemia is negative

    • A consequence of

      • Relative resistance to RBC production in response to erythropoietin

      • Decrease in erythropoietin production relative to the nephron mass

      • Negative erythropoietic influence of higher levels of chronic inflammatory cytokines in older adults

      • Presence of various somatic mutations in myeloid genes typically associated with myeloid neoplasms; this condition is referred to as clonal cytopenias of undetermined significance (CCUS), which has a 15–20% per year rate of transformation to a myeloid neoplasm, such as the myelodysplastic syndrome

    • Serum iron is normal

Clinical Findings

  • Clinical features are those of causative condition

  • Suspect diagnosis in patients with known chronic diseases


  • Hematocrit rarely falls below 60% of baseline (except in end-stage kidney disease)

  • Mean corpuscular volume usually normal or slightly low

  • RBC morphology usually normal; reticulocyte count mildly decreased or normal

  • Low serum iron, low transferrin saturation

  • Normal or increased serum ferritin; serum ferritin < 30 mcg/L suggests coexistent iron deficiency

  • Normal or increased iron stores

  • CCUS is diagnosed by sending a blood or bone marrow sample for myeloid gene sequencing

  • Note: Certain circumstances of iron-restricted erythropoiesis (such as malignancy) partially respond to parenteral iron infusion even when the iron stores are replete due to the acute distribution of iron to erythropoietic progenitor cells


  • In most cases, no treatment of the anemia of chronic disease is necessary

  • Primary management is to address the condition causing it

  • When the anemia is severe or is adversely affecting the patient's quality of life or functional status, either RBC transfusions or parenteral recombinant erythropoietin (epoetin alfa or darbepoetin) is warranted

  • Recombinant erythropoietin

    • Indications

      • Hemoglobin < 10 g/dL

      • Anemia due to rheumatoid arthritis, inflammatory bowel disease, hepatitis C, administration of zidovudine ...

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