Anemia of chronic disease (ACD) is frequently found in patients with chronic immune activation. Since most studies on ACD pathophysiology were performed with cell culture or animal models but not in humans, we examined 37 ACD patients suffering from autoimmune diseases or infections, 10 subjects with irondeficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS), and 27 age-matched controls. Although hemoglobin concentrations were comparable between ACD and IDA patients, the latter presented with significantly higher serum erythropoietin concentrations than ACD patients. The significant negative correlation between erythropoietin and hemoglobin levels observed in IDA patients was also found in a group of anemic but not hypoferremic hereditary spherocytosis subjects, but not in ACD patients. Increased serum concentrations of the hepcidin precursor prohepcidin were paralleled by a decreased expression of the iron exporter ferroportin in circulating monocytes of ACD patients. IntroductionAnemia of chronic disease (ACD), also termed as anemia of inflammation, is likewise the most frequent anemia in hospitalized patients. This mild to moderate normocytic to microcytic anemia is found with a frequency between 8% and 95% in patients suffering from diseases that are associated with chronic immune activation, such as autoimmune disorders including rheumatoid arthritis and malignancies and chronic infections including HIV. [1][2][3] At least 3 major immunity-driven mechanisms contribute to the development of ACD. These include the development of hypoferremia with subsequent limitation of iron availability for erythroid progenitor cells, antiproliferative effects of cytokines toward the proliferation and differentiation of erythroid progenitor cells, and, last but not least, an impaired production and reduced biologic activity of erythropoietin (Epo).The development of hypoferremia results from a complex interaction of acute-phase proteins and cytokines together with an anticipated reduction in the lifespan of erythrocytes. Thereby, the absorption of iron from the gut is reduced while iron acquisition and retention by cells of the reticulo-endothelial system (RES) is greatly stimulated, leading to the development of iron-restricted erythropoiesis and anemia. The liver-derived acute-phase protein hepcidin plays a central role in this setting, since it reduces both duodenal iron absorption and iron export from monocytes/ macrophages. [4][5][6] These effects can be referred to as interaction of hepcidin with the transmembrane protein ferroportin, 7 which is responsible for the transfer of iron from enterocytes and monocytes/ macrophages to the circulation. 8,9 The expression of hepcidin by hepatocytes is induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6), resulting in the development of hypoferremia in mice within a few hours after injection. 6,10 Moreover, proinflammatory and anti-inflammatory cytokines play an important role in the pathophysiology of ACD by increasing iron accumulation and sto...

BackgroundHereditary spherocytosis is a very heterogeneous form of hemolytic anemia. The aim of this study was to relate the type of molecular defect with clinical and hematologic features and response to splenectomy using information from a large database of patients.

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Summary The clinical course of thrombotic thrombocytopenic purpura (TTP) is characterized by recurrent disease episodes in up to 50% of cases. The clinical presentation and severity of different TTP episodes have not been systematically compared. Laboratory and clinical information from 51 patients with recurrent disease, derived from 136 patients with TTP included in the Milan TTP registry (URL: http://www.ttpdatabase.org), were used to compare mortality, symptoms and disease‐related laboratory measurements in different disease episodes. The prevalence of severe neurological symptoms (coma, seizures, and focal neurological defects) was significantly lower in recurrences than in the first episode. Platelet counts and haemoglobin levels at presentation were higher in recurrences than in the first disease episode, and lactate dehydrogenase levels were lower. Also, mortality tended to be lower in the second and third disease episodes than in the first. Recurrences of TTP are generally milder than first episodes. These differences in severity should be taken into account in clinical research on TTP and in patient management.