Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action

Abstract

Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin <100 µg/L and/or transferrin saturation <20%. Iron parameters remain, however, insufficiently assessed in patients with chronic inflammatory conditions. Indeed, clinical symptoms of iron deficiency, such as fatigue, are not specific and often confused with those of the primary disease. Iron repletion, preferably by the intravenous route to bypass tissue sequestration, improves clinical signs and quality of life. Because of the negative impact of iron deficiency on chronic inflammatory diseases and the efficacy of intravenous iron repletion, screening of iron parameters should be part of the routine examination of all patients with chronic inflammatory diseases.

Circulating Levels of Ferritin, RDW, PTLs as Predictive Biomarkers of Postoperative Atrial Fibrillation Risk after Cardiac Surgery in Extracorporeal Circulation

“…They can evidence not only an iron deficiency status accompanied by clinical symptoms (i.e., fatigue, which is not specific and often confused with the symptoms of primary diseases), but they can also provide information about the clinical status of a patient, an individual, related to degree of systemic inflammation. the status of iron deficiency is recurrent in patients with chronic inflammatory diseases (such as chronic cardiovascular diseases [12][13][14], i.e., coronaropathies, valvopathies, and ascending aorta aneurysms, affecting the patients of our study), that significantly correlates with their severity. Iron deficiency is mediated by high systemic levels of cytokines, which evocate a parallel increase of hepcidin concentrations.…”

“…The development of iron deficiency, even if functional, exacerbates underlying chronic diseases, alters erythropoiesis, and represents an independent factor of morbidity and mortality. In daily practice, the the iron body status is evaluated by detecting ferritin concentrations, because it reflects the iron body storage and transferrin saturation, which reproduces the transport of iron [12,13].…”

The Role of Ferritin in Health and Disease: Recent Advances and Understandings

“…Ferritin sequesters excess intracellular iron and stores it in a redox-inactive form for future use in conditions of deficiency or high demand. Cellular and systemic ferritin levels are not only crucial indicators of iron status but are also important markers of inflammatory [ 12 ], immunological [ 13 ], and malignant disorders [ 14 , 15 ]. Genetic alterations of ferritin are often associated with severe pathologies, and homozygous FTH deletion in mice is incompatible with life [ 16 ].…”

Effects and Safety of Oral Iron for Heart Failure with Iron Deficiency: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

“…Transferrin is mainly responsible for the delivery of iron via transferrin-receptor that is a potential biomarker to identify iron deficiency in HF patients [ 12 ]. Moreover, high level hepcidin, which is a vital regulator of systemic iron metabolism, can block iron absorption, ultimately leading to iron deficiency [ 13 , 14 ]. Iron deficiency can cause increased cardiac output, left ventricular hypertrophy, and left ventricular dilation, leading to symptomatic chronic heart failure [ 11 ].…”