Strictly speaking, anemia of chronic inflammation, previously called anemia of chronic disease, is not a microcytic anemia. When found in the absence of other anemia causes, ACI is usually normocytic, normochromic with normal RBC indices. Because it so often coexists with iron deficiency anemia and is directly related to iron availability, it is often categorized with other microcytic anemias. ACI is the second most common cause of anemia worldwide and is common in hospitalized patients.6
ACI is due to impaired ferrokinetics. Hepcidin, a hormone produced by the liver, causes the degradation of the transmembrane protein ferroportin that normally exports iron from enterocytes into the blood. This results in a decrease in the iron absorbed into the blood from the intestine. In other words, hepcidin has an inverse relationship with available iron. When body iron levels decrease, hepcidin production also decreases so that more iron becomes available in the blood.
Hepcidin is an acute-phase protein so during inflammation more is produced. Regardless of the levels of iron, this increase in hepcidin causes a decrease in the release of iron from iron stores. While not a problem during short periods of inflammation, chronic inflammatory conditions result in anemia.
It is also known that lactoferrin found in the granules of neutrophils has an avidity for iron that is greater than transferrin. Lactoferrin works to prevent phagocytized bacteria from using intracellular iron and when released into the blood upon neutrophil death may play a minor role contributing to the anemia of ACI.
In addition to the impact of hepcidin and lactoferrin, erythropoiesis is decreased in the presence of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interferon-gamma.
Finally, the RBC life cycle is shortened but the mechanism behind this is still not clear.
The best treatment for ACI is dependent on the cause of inflammation. However, for select individuals, therapeutic administration of erythropoietin will show effective results.
6. Keohane, E. M., Otto, C.N., Walenga, J. M. (2019). Rodak's Hematology Clinical Principles and Applications. St. Louis., Elsevier, 6th Edition.
