Anemia of Inflammation

Anemia of inflammation (AI), also known as anemia of chronic disease, is the most common anemia in hospitalized patients and considered to be the second most common anemia worldwide after iron deficiency anemia (IDA). The hallmark of AI is iron restriction within macrophages of the mononuclear phagocyte system (MPS) resulting in hypoferremia and hyperferritinemia together with suppression of erythropoiesis and shortened erythrocyte lifespan. Symptoms are comparable to other anemia entities and often related to the underlying disease. Patients usually present with normocytic, normochromic, hypoproliferative, mild-to-moderate anemia, reduced circulating iron levels (transferrin saturation), and increased stored iron (serum ferritin). However, AI is often associated with true iron deficiency on the basis of inflammatory diseases and blood losses of different reasons, which is why the correct identification of these patients, and their iron needs is a diagnostic challenge. Treatment of the underlying disease that causes immune activation is the primary therapeutic approach for AI which normally results in its resolution over time. Concomitant pathologies and factors contributing to the AI severity should be considered and, when feasible, specifically corrected. Iron supplementation is the first-line therapy for AI+IDA patients, while intravenously applied iron is trapped in macrophages of the MPS during advanced inflammation in patients with solely AI, whereas orally supplemented iron is not properly absorbed. Effectiveness of erythropoiesis-stimulating agents is limited in AI due to inflammation-mediated suppression of erythropoietin (Epo) signaling and impaired erythroid cell proliferation and differentiation, while red blood cell transfusion should primarily be used in life-threatening anemia. Clinical studies on hypoxia-inducible factor prolyl hydroxylase inhibitors seem promising although concerns about their safety and efficacy in AI arose within recent years. New treatment strategies aim to modify the hepcidin-ferroportin axis, yet clinical trials are still outstanding.