Anemia of Chronic DiseaseZInflammation

GENERAL PRINCIPLES

• Anemia of chronic disease (ACD) often develops in patients with long-standing inflammatory diseases, malignancy, autoimmune disorders, and chronic infection.

• Etiology is multifactorial, including defective iron mobilization during erythropoiesis, inflammatory cytokine-mediated suppression of erythropoiesis, and impaired EPO response to anemia. Hepcidin is a critical regulator of iron homeostasis and is normally low when iron is deficient, allowing for increased iron absorption and utilization. Chronic inflammation increases hepcidin levels and causes a functional iron deficiency due to impaired iron recycling and utilization. Hepcidin is renally cleared,

suggesting a role in anemia of chronic renal disease.

DIAGNOSIS

• Anemia is normocytic in 75% of cases and microcytic in the remainder of cases.

• The soluble transferrin receptor level is helpful in differentiating ACD (normal) and iron deficiency (elevated) when the ferritin is indeterminate. Measurement of serum hepcidin may become part of the standard evaluation of anemia when the assay becomes widely available in the future, but currently is not utilized clinically.

• Iron studies may show low serum iron and TIBC.

TREATMENT

• Therapy for ACD is directed toward the underlying disease and eliminating exacerbating factors such as nutritional deficiencies and marrow-suppressive drugs.

• Ferritin level below 30 ng/mL suggests coexisting iron deficiency and should be treated with supplemental iron. Clinical responses to IV iron therapy may occur in patients with ferritin levels up to 100 ng/mL. Enteral iron is typically ineffective in ACD because of reduced intestinal absorption of iron.