-
1.
Ferritin - from iron, through inflammation and autoimmunity, to COVID-19.
Mahroum, N, Alghory, A, Kiyak, Z, Alwani, A, Seida, R, Alrais, M, Shoenfeld, Y
Journal of autoimmunity. 2022;:102778
-
-
Free full text
-
Abstract
While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.
-
2.
Iron Homeostasis and Ferritin in Sepsis-Associated Kidney Injury.
McCullough, K, Bolisetty, S
Nephron. 2020;(12):616-620
Abstract
Sepsis associated acute kidney injury (SA-AKI) is a common clinical syndrome that occurs among hospitalized patients and significantly impacts mortality. Furthermore, survival after sepsis is intricately dependent on recovery of kidney function. In this review, we discuss the role of iron imbalance in mediating the pathogenic events during sepsis. Intracellular ferritin serves as a repository for iron and prevents iron-mediated injury and may limit the availability of iron to pathogens. Circulating levels of ferritin also increase during sepsis and often correlate with severity of sepsis. Herein, we examine preclinical and clinical data and discuss recent findings that suggest immunomodulatory roles for ferritin. We also discuss the possible mechanistic roles for ferritin in mitigating the pathogenic sequelae of sepsis and highlight current gaps in knowledge.
-
3.
Iron in the General Population and Specificities in Older Adults: Metabolism, Causes and Consequences of Decrease or Overload, and Biological Assessment.
Manckoundia, P, Konaté, A, Hacquin, A, Nuss, V, Mihai, AM, Vovelle, J, Dipanda, M, Putot, S, Barben, J, Putot, A
Clinical interventions in aging. 2020;:1927-1938
Abstract
Iron is involved in many types of metabolism, including oxygen transport in hemoglobin. Iron deficiency (ID), ie a decrease in circulating iron, can have severe consequences. We provide an update on iron metabolism and ID, highlighting the particularities in older adults (OAs). There are three iron compartments in the human body: 1) the functional compartment, which consists of heme proteins including hemoglobin, myoglobin and respiratory enzymes; 2) iron reserves (IR), which consist mainly of liver stocks and are stored as ferritin; and 3) transferrin. There are two types of ID. Absolute ID is characterized by a decrease in IR. Its main pathophysiological mechanism is bleeding, which is often digestive and can be due to neoplasia, frequent in OAs. Biological assessment shows low serum ferritin and transferrin saturation (TS) levels. Furthermore, hypochromic microcytic anemia is frequent, and the serum-soluble transferrin receptor (sTfR) level is high. Functional ID, in which IR are high or normal, is due to inflammation, which is also frequent in OAs, particularly in its chronic form. Biological assessments show high serum ferritin, normal or low TS, and normal sTfR levels. Moreover, C-reactive protein is elevated, and there is moderate non-regenerative non-macrocytic anemia. The main characteristics of iron metabolism anomalies in the elderly are the high frequency of ID (20% of ID with anemia in adults ≥85 years) and the severity of its consequences, which include cognitive impairment in case of ID or iron overload and decrease of physical activity in case of ID. In conclusion, causes of ID are frequently intertwined in OAs as a result of the polymorbidity that characterizes them. ID can have dramatic consequences, especially in frail OAs. Thus, measuring the appropriate biological markers prevents errors in the positive diagnosis of ID type, clarifies etiology, and informs treatment-related decision-making.
-
4.
COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy.
Perricone, C, Bartoloni, E, Bursi, R, Cafaro, G, Guidelli, GM, Shoenfeld, Y, Gerli, R
Immunologic research. 2020;(4):213-224
-
-
Free full text
-
Abstract
SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still's disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.
-
5.
Hyperferritinemia in critically ill COVID-19 patients - Is ferritin the product of inflammation or a pathogenic mediator?
Gómez-Pastora, J, Weigand, M, Kim, J, Wu, X, Strayer, J, Palmer, AF, Zborowski, M, Yazer, M, Chalmers, JJ
Clinica chimica acta; international journal of clinical chemistry. 2020;:249-251
-
6.
Iron Deficiency in Heart Failure: An Overview.
von Haehling, S, Ebner, N, Evertz, R, Ponikowski, P, Anker, SD
JACC. Heart failure. 2019;(1):36-46
Abstract
Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physical well-being and reduced quality of life. Cutoff values have been identified for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin, <100 μg/l, or ferritin, 100 to 300 μg/l, with transferrin saturation of <20%. Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products. Most clinical studies have been performed using ferric carboxymaltose with good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class. Data from meta-analyses also suggest beneficial effects for hospitalization rates for heart failure and reduction in cardiovascular mortality rates. A prospective trial to investigate effects on morbidity and mortality is currently ongoing. This paper highlights current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options.
-
7.
Investigation and management of a raised serum ferritin.
Cullis, JO, Fitzsimons, EJ, Griffiths, WJ, Tsochatzis, E, Thomas, DW, ,
British journal of haematology. 2018;(3):331-340
-
-
Free full text
-
Abstract
Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.
-
8.
Hyperferritinemia in patients with nonalcoholic fatty liver disease.
Barros, RK, Cotrim, HP, Daltro, CH, Oliveira, YA
Revista da Associacao Medica Brasileira (1992). 2017;(3):284-289
Abstract
OBJECTIVE In liver diseases, hyperferritinemia (HYF) is related to injured cells in acquired and genetic conditions with or without iron overload. It is frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it is necessary to define the mean of HYF to establish the better approach for them. The present study evaluated the significance of elevated ferritin in patients with NAFLD and steatohepatitis (NASH). METHOD The review was performed using search instruments of indexed scientific material, including MEDLINE (by PubMed), Web of Science, IBECS and LILACS, to identify articles published in Portuguese, English and Spanish, from 2005 to May, 2016. Studies eligible included place and year of publication, diagnose criteria to NAFLD, specifications of serum ferritin measurements and/or liver histopathologic study. Exclusion criteria included studies with patients with alcohol consumption ≥ 20 g/day and other liver diseases. RESULTS A total of 11 from 30 articles were selected. It included 3,564 patients and they were cross-sectional, retrospective, case series and case-control. The result's analyses showed in 10 of these studies a relationship between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis and insulin resistance. CONCLUSION Hyperferritinemia in patients with NAFLD/NASH is associated more frequently with hepatocellular injury than hemochromatosis. These data suggest the relevance to evaluate carefully HYF in patients with NAFLD/NASH to establish appropriate clinical approach.
-
9.
Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.
Daru, J, Allotey, J, Peña-Rosas, JP, Khan, KS
Transfusion medicine (Oxford, England). 2017;(3):167-174
-
-
Free full text
-
Abstract
The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL-1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem.
-
10.
Serum ferritin as an indicator of iron status: what do we need to know?
Daru, J, Colman, K, Stanworth, SJ, De La Salle, B, Wood, EM, Pasricha, SR
The American journal of clinical nutrition. 2017;(Suppl 6):1634S-1639S
-
-
Free full text
-
Abstract
Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of <15 μg/L is a specific but not sensitive cutoff, although evidence is limited. Data from women during pregnancy or from young children are especially uncommon. Most data are from studies conducted >30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy.