No abstract

Iron deficiency is a common condition increasingly diagnosed and treated by gastroenterologists. The most common presentation of iron deficiency is anaemia; however, it is a systemic disorder affecting multiple aspects of health in various organs. Iron is an essential element, with iron-containing proteins exerting a variety of vital functions, including oxygen transport, cellular respiration, intermediary metabolism, regulation of transcription and DNA repair. Major pathways of iron utilisation and production of iron-containing proteins include iron sulphur cluster biosynthesis, haem synthesis and storage within ferritin. The main site of iron absorption is the small intestine, but most iron is recycled by the monocyte-macrophage system via phagocytosis of senescent erythrocytes. Hepcidin, the key iron-regulating peptide binds to the iron exporter ferroportin and leads to its degradation, thereby inhibiting intestinal iron absorption and cellular export. Hepcidin levels are regulated on a transcriptional level by various stimuli, including transferrin saturation, erythropoietic activity, hypoxia and inflammation. Iron deficiency evokes adaptive responses resulting in alteration of cellular metabolism, changes in gene expression, activation of signalling pathways, cell cycle regulation, differentiation and cell death. Such responses are mediated by a number of iron-sensitive signalling pathways, including the IRE/IRP system, HIF and haem signalling. This review provides a molecular perspective for the clinician and highlights important biological aspects of iron deficiency.

SummaryIron deficiency and iron deficiency-associated anemia are common complications in cancer patients. Most iron deficient cancer patients present with functional iron deficiency (FID), a status with adequate storage iron, but insufficient iron supply for erythroblasts and other iron dependent tissues. FID is the consequence of the cancer-associated cytokine release, while in absolute iron deficiency iron stores are depleted resulting in similar but often more severe symptoms of insufficient iron supply. Here we present a short review on the epidemiology, pathophysiology, diagnosis, clinical symptoms, and treatment of iron deficiency in cancer patients. Special emphasis is given to intravenous iron supplementation and on the benefits and limitations of different formulations. Based on these considerations and recommendations from current international guidelines we developed recommendations for clinical practice and classified the level of evidence and grade of recommendation according to the principles of evidence-based medicine.

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency‐induced thrombocytosis. Within few weeks, iron‐depleted diet caused iron deficiency in young Sprague–Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron‐depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency‐induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Am. J. Hematol. 89:524–529, 2014. © 2014 Wiley Periodicals, Inc.