Abstract
Anemia is very common in patients with inflammatory disorders. Its prevalence is associated with severity of the underlying disease, and it negatively affects quality of life and cardio-vascular performance of patients. Anemia of inflammation (AI) is caused by disturbances of iron metabolism resulting in iron retention within macrophages, a reduced erythrocyte half-life, and cytokine mediated inhibition of erythropoietin function and erythroid progenitor cell differentiation. AI is mostly mild to moderate, normochromic and normocytic, and characterized by low circulating iron, but normal and increased levels of the storage protein ferritin and the iron hormone hepcidin. The primary therapeutic approach for AI is treatment of the underlying inflammatory disease which mostly results in normalization of hemoglobin levels over time unless other pathologies such as vitamin deficiencies, true iron deficiency on the basis of bleeding episodes, or renal insufficiency are present. If the underlying disease and/or anemia are not resolved, iron supplementation therapy and/or treatment with erythropoietin stimulating agents may be considered whereas blood transfusions are an emergency treatment for life-threatening anemia. New treatments with hepcidin-modifying strategies and stabilizers of hypoxia inducible factors emerge but their therapeutic efficacy for treatment of AI in ill patients needs to be evaluated in clinical trials.
Highlights
Anemia is common in patients with acute or chronic inflammatory disorders, and termed as anemia of chronic disease (ACD) or anemia of inflammation (AI) [1,2,3,4]
Linked to infectious diseases, cancer or autoimmune disorders [6,7,8,9,10,11], AI is common in patients with chronic kidney disease (CKD) [12,13,14,15], coronary artery disease (CAD) [16], chronic heart failure (CHF) [17,18], advanced atherosclerosis [19] or chronic pulmonary disease [20,21,22]
280 million hemoglobin molecules, which in turn contain four heme-subunits with central iron atoms. These iron atoms represent the binding sites for oxygen providing more than a billion oxygen binding sites per erythrocyte. [36,37] The daily iron demand for metabolic processes in adult humans is about 20–30 mg. Most of this daily required iron comes from macrophages, which recycle iron by phagocytosis of senescent erythrocytes, while about 10% of the daily needs are provided by duodenal absorption of iron from the diet
Summary
Anemia is common in patients with acute or chronic inflammatory disorders, and termed as anemia of chronic disease (ACD) or anemia of inflammation (AI) [1,2,3,4]. In cancer patients for instance, anemia is a common comorbidity found in approximately 40–60% of patients with malignancies mostly due to AI but often aggravated by anti-cancer therapy [27,28]. It is associated with fatigue and poor QoL [25,29] as well as impaired local tumor control [30,31]. This review will first summarize the physiology of iron metabolism and erythropoiesis, as well as pathophysiology and diagnosis of AI and focus on established therapies and new therapeutic options, which are currently evaluated in clinical or laboratory studies in patients with anemia and inflammatory disease
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