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 production is reduced and RBC mass decreases in response to a diminished signal for RBC 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 neoplasms

  • 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 (MCV) 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 rapid distribution of parenteral 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 ...