Anemia of Chronic Disorders: New Diagnostic Tools and New Treatment Strategies

Anemia in the setting of chronic inflammatory disorders is a very frequent clinical condition, which is, however, often neglected or not properly treated given the problems often caused by the diseases underlying the development of anemia. Mechanistically, anemia is mainly caused by inflammation-driven retention of iron in macrophages making the metal unavailable for heme synthesis in the course of erythropoiesis, and further by impaired biological activity of the red blood cell hormone erythropoietin and the reduced proliferative capacity of erythroid progenitor cells. Anemia can be aggravated by chronic blood loss, as found in subjects with gastrointestinal cancers, inflammatory or infectious bowel disease, or iatrogenic blood loss in the setting of dialysis, all resulting in true iron deficiency. The identification of such patients is a clinical necessity because these individuals need contrasting therapies in comparison to subjects suffering from only classical anemia of chronic disorders. The diagnosis is challenging because no state of the art laboratory test is currently available that can clearly separate patients with inflammatory anemia from those with additional true iron deficiency. However, based on our expanding knowledge on the pathophysiology of inflammatory anemia, new diagnostic markers, including the iron-regulatory hormone hepcidin, and hematologic parameters emerge. Apart from traditional anemia treatments such as blood transfusions, recombinant erythropoietin, and iron, including new high-molecular-weight formulations, new therapeutics are currently under preclinical and clinical evaluation. These novel compounds aim at correcting anemia by multiple pathways, including antagonizing the inflammation- and hepcidin-driven retention of iron in the monocyte-macrophage system and thereby promoting the supply of iron for erythropoiesis or by stimulating the endogenous formation of erythopoietin via stabilization of hypoxia-regulated factors.