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

Diagnosis

• 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

Treatment

• 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 ...