Absolute Iron Deficiency Research Articles

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia.

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.

Iron deficiency in elderly patients: use of biomarkers

Iron deficiency, due to blood loss or malabsorption, is commonly observed in geriatric practice. In elderly people, association of inflammatory diseases to iron loss makes diagnosis of absolute iron deficiency sometimes difficult. In case of inflammation, the interpretation of usual biomarkers of iron deficiency (serum ferritin, transferrin saturation, serum iron) may be difficult. The recent discovery of the role of hepcidine in the iron homeostasis, in physiological and pathological situation, contributes to better understanding of the iron regulation. The aim of this short paper is to underline some specificities of elderly iron physiology, to explain hepcidine's role in physiological and pathological situations and to propose a diagnostic approach for a better interpretation of usual biomarkers, in order to differentiate absolute iron deficiency and functional iron deficiency.

Cost-minimization analysis of the carboxymaltose ferric (i.v.) Compared with sacarato ferric (i.v.) in the treatment of anemia under suplementary health care perspective

Absolute iron deficiency related to depletion of iron stores or functional iron deficiency are the main causes of anemia, which can trigger hospitalization and even mortality. International guidelines recommend intravenous (IV) iron therapy for several chronic conditions. Intravenous iron is more effective, better tolerated, and improves the quality of life to a greater extent than oral iron supplements. Ferric carboxymaltose (FCM) and iron sucrose (IS) are IV iron drugs available in the Brazilian market. Considering this scenario the purpose of the study is to perform a cost minimization analysis of FCM versus IS under the supplementary health setting. Due to no non-inferiority study design comparing both IV therapies, a cost-minimization analysis was conducted. Treatment expenditures were accounted considering drugs acquisition costs and infusion related costs. Drugs ex-factory prices were obtained in official price list. Infusion fees were accessed through research conducted in 36 private hospitals distributed in service categories. In each institution the information collected was: place of infusion, materials, medical honoraries, room fee and price lists. An average patient was assumed (70kg; Hb≤10,5g/dL) which would receive a total iron dose of 1,000mg in both regimens. According to label, FCM can be administrated in a single dose whereas IS requires 5 infusions of 200 mg iron given up twice weekly. Deterministic one-way sensitivity analysis was performed. Costs were reported in Brazilian currency. Treatment cost for FCM (BRL927.69) was lower than IS (BRL 1,184.97), due to more infusions required for treatment with IS. The number and cost of the infusions were the most influential parameters in the analysis, and even with variations of ± 20% in all parameters, treatment results with FCM remained favorable. FCM represents a cost-saving option compared with other IV therapy alternative used in the management of anaemia in the Brazilian Supplementary Health System.

Iron metabolism and iron supplementation in cancer patients.

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.

24 Anaemia in heart failure unit St. Michaels hospital dun laoghaire

Background Iron deficiency anaemia is a frequent finding in adults with heart failure (HF). The prevalence varying depending upon the population studied. 1,2 The recent FAIR-HF trial, demonstrates the importance of iron metabolism in patients with HF. 3 Moreover, that a work-up evaluation for absolute or functional iron deficiency should be considered, and implementation of IV iron replacement for symptomatic improvement. In this audit we wish to evaluate the prevalence of anaemia and iron deficiency in our unit Method This was a prospective single centre audit between 21 October and 18 November 2014. The cycle was repeated between 26 March and 26 April 2015. The audit standard was the WHO definition of anaemia. Results Part 1: Demographics During cycle 1 Population: 86 patients were worked up for anaemia and iron deficiency. The average follow up time in Heart Failure Unit was 19.6 months There were more males than females in our population. Only one female patient is still menstruating. 74% of our population are HfREF (n = 64) versus 26% HfPEF (n = 22). During cycle 2 Population: 56 patients were worked up for anaemia and iron deficiency. The average follow up time in Heart Failure Unit was 20.4 months. There were more males than females in our population. 57% of our population are HfREF (n = 31) versus 43% HfPEF (n = 23). Part 2: Prevalence and incidence The prevalence of anaemia in our cohort was 48% during cycle 1 and 64.8% during cycle 2. Previous studies have found that the incidence of anaemia appears to increase with worsening functional class (from 9% for NYHA class I to 79% for class IV in one report). 4,5 We found no association between the incidence of anaemia for NYHA, BNP or EF in our cohort. Part 3: Haematinic Screen Haematinic screens were not routinely ordered on all anaemic patients during cycle 1. No haematinic screen was found for 15 anaemic patients, an incomplete screen was carried out on 9 anaemic patients and a complete anaemic screen on 17 patient. A complete haematinic screen was carried out on 8 patients with normal Hb levels. Iron deficency was detected in 17 patients. Five patient with iron deficency were noted to have a normal Hb level. During cycle 2 and implementation of a routine strategy of a haematinic screening at initial programme visit or at annual review, if no such screen were on record, all patients had a haematinic screen. Summary Iron deficiency management is not incorporated in the current ESC HF guidelines. 6 However, recent studies have raised interest in the importance in symptomatic and QUAL in of HfREF patients, and experts anticipate it’s inclusion in future guidelines. Further given that there are few treatment strategies for HfPEF patients, management of iron deficiency in this cohort would be an area of interest to access any symptomatic and other clinical benefit. In this audit we successfully implemented a strategy of routine screening for iron deficiency, to capture all patients in both HfREF and HfPEF patients. Importantly, at present our cohort our stable from a heart failure perspective. In future direction and management of these patients we aim to implement a strategy of IV iron replacement based on recent FAIR-HF and CONFIRM-HF studies. 3,7 References De Silva R, Rigby AS, Witte KK, et al . Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol. 2006; 98 :391–398 Westenbrink BD, Visser FW, Voors AA, et al . Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur Heart J. 2007; 28 :166–171 Anker SD, Comin Colet J, Filippatos G, et al . Rationale and design of Ferinject assessment in patients with iron deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail . 2009; 11 :1084–1091 Silverberg DS, Wexler D, Sheps D, et al . The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol . 2001; 37 :1775–1780 Van der Meer P, Groenveld HF, Januzzi JL Jr, et al . Erythropoietin treatment in patients with chronic heart failure: a meta-analysis. Heart 2009; 95 :1309–1314 McMurray J, Adamopoulos S, Anker S, et al . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur Heart J . 2012; 33 :1787–1847 Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al . Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J . 2015; 36 (11):657–68

Thresholds of iron markers for iron deficiency erythropoiesis—finding of the Japanese nationwide dialysis registry

Reportedly, serum ferritin levels are much lower in Japanese hemodialysis (HD) patients than their Western counterparts. Therefore, the cutoff values of ferritin and transferrin saturation (TSAT) for iron deficiency might differ from other countries. We conducted a cross-sectional observational study using the Japanese nationwide registry data. We enrolled 142,339 maintenance HD patients and assessed the association between these markers, hemoglobin (Hb), and erythropoiesis-stimulating agent (ESA) resistance index (ERI) utilizing restricted cubic spline analyses. Median ferritin and TSAT levels were 73 (IQR: 31–158) ng/ml and 23.7 (16.8–32.0)%, respectively. These lower ferritin ranges may possibly stem from a lower inflammatory state in Japanese patients, as shown in median CRP of 1.0 mg/l. An adjusted nonlinear association between Hb and TSAT showed that Hb levels drop with the decrease in TSAT below 20%, regardless of serum ferritin levels, suggesting the absolute iron deficiency cutoff as 20% for TSAT. In patients with TSAT >20%, the association between Hb and ferritin levels is nearly flat, whereas in patients with TSAT <20%, ferritin <50 ng/ml was associated with low Hb. In long-acting ESAs-users with TSAT >20%, U-shaped relationship was observed between ERI and ferritin with the bottom of ERI around 100 ng/ml of ferritin, possibly because high ferritin levels reflected an inflamed state leading to hyporesponsiveness to ESA. The patient subgroup with TSAT <20% and ferritin >100 ng/ml had significantly higher ERIs compared with the subgroup with TSAT >20% and ferritin <100 ng/ml, implying that TSAT, rather than ferritin, should be a primary iron marker predicting ESA response.

The role of iron supplements in the treatment of anemia in cancer patients.

The problem of anemia in cancer patients is relevant and multilateral. One of the causes of anemia is iron deficiency. The absolute or functional iron deficiency reduces the efficiency of recombinant erythropoietin used for the treatment of chemotherapy-induced anemia. Numerous studies have shown that intravenous forms of iron, as opposed to oral, effectively replenish iron deficiency necessary for optimal erythropoiesis. Modern American and European recommendations (ESMO, NCCN) for the treatment of anemia in cancer patients include the mandatory use of intravenous forms of iron.

Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

ObjectiveThe aim of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters to identify three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency.MethodsPeripheral blood cells from 117 adult patients with anemia were classified according to iron status, inflammation, and hemoglobinopathies as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β-thalassemia (n = 25). The percentage of microcytic erythrocytes, hypochromic erythrocytes, and the levels of hemoglobin in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating anemia.ResultsThere was no difference between the groups of iron deficiency and anemia of chronic disease associated with absolute iron deficiency for any of the parameters. The percentage of hypochromic erythrocytes was the best parameter to identify absolute iron deficiency in patients with anemia of chronic disease (area under curve = 0.785; 95% confidence interval: 0.661–0.909 with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic erythrocyte count minus hypochromic erythrocyte count was very accurate to differentiate iron deficiency anemia from heterozygous β-thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005 with a sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8).ConclusionThe erythrocyte and reticulocyte indices are moderately good to identify absolute iron deficiency in patients with anemia of chronic disease.

Comment on: Evaluation of erythrocyte and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease.

The article on the evaluation of the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease (ACD), and anemia of chronic disease associated with absolute iron deficiency by Torino et al.1 is very valuable. Automated reticulocyte counts are widely used in the clinical laboratory due to their greater precision, accuracy and reproducibility compared to those obtained using the microscope. The most important benefit of automated methods is the greater precision of counts. By analyzing a much greater number of reticulocytes (more than ten thousand), the statistical error is minimized.2 Visual microscopy is still recommended as the comparability method for reticulocytes, despite studies showing that the variation coefficient (VC) ranges from 20% to 40%. Fully automated methods have eliminated inter-observer variability and subjectivity and substantially reduced turnaround time. Automated methods employ a wide variety of reagents for reticulocyte RNA and these show different sensitivity on binding to RNA.3 Therefore, although automated flow cytometric analysis has led to a significant advance in reticulocyte counting, some limitations still persist in comparability across different laboratories

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

Background/Aims: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

Interleukin 17 and Pro-hepcidin in Anemia and Erythropoietin Responsiveness of Chronic Kidney Disease Patients Treated with Hemodialysis

Background: Monocytes and granulocytes, activated by contact with hemodialysis membranes, generate increased cytokine secretion, an important key in pathogenesis of anemia and erythropoietin (rHuEPO) resistance. We aimed to examine the correlation of IL-17 and pro-hepcidin with anemia of chronic kidney disease (CKD) patients treated with hemodialysis(HD). Method: 69 HD patients were included. Exclusion criteria were: neoplasia, acute infections, blood loss, absolute iron deficiency. IL-17 and pro-hepcidin were determined. Hemoglobin, ferritin, transferrin and transferrin saturation were measured. rHuEPO responsiveness index was calculated. A poor response to rHuEPO was defined as rHuEPO responsiveness index>200. Results: Mean level of IL-17 was 33.3 ± 5.1 pg/ml and pro-hepcidin was 336.6 ± 23.7 pg/ml. IL-17 and pro-hepcidinnegatively correlated with hemoglobin (R0.503, p 200 had higher pro-hepcidin (432.5 ± 25 vs. 157.5 ± 12 pg/ml, p<0.001), increased IL-17 (27 ± 1.9 vs. 4.9 ± 0.3 pg/ml, p<0.001), and lower iron biodisponibility (transferrin saturation 18 ± 1.6% vs.31 ± 1.2%; p<0.001) than those with rHuEPO responsiveness index<200. IL-17 positively correlated with prohepcidin (R0.454, p<0.001). Conclusion: High levels of IL-17 and pro-hepcidin are both correlated with low hemoglobin, poor response to rHuEPO and decreased iron biodisponibility in hemodialysis patients.

Hemoglobina reticulocitaria: un nuevo parámetro del hemograma de gran valor en el diagnóstico y manejo de la eritropoyesis deficiente en hierro

La incorporación de los autoanalizador de hematología al laboratorio clínico no solo mejoró la calidad de los resultados de los parámetros convencionales del hemograma sino que ha permitido, especialmente con aquellos de última generación, introducir nuevos parámetros de gran utilidad clínica. Uno de los nuevos parámetros es la hemoglobina reticulocitaria, la cual se vislumbra como una potente herramienta en el diagnóstico y el manejo de la eritropoyesis deficiente en hierro en sus diferentes manifestaciones, en particular la deficiencia absoluta de hierro, la deficiencia funcional de hierro y el secuestro del hierro. La hemoglobina reticulocitaria en todos los casos en donde hay eritropoyesis deficiente en hierro es el primer parámetro detectable en el hemograma y, a su vez, es el primero que se normaliza cuando la terapia administrada ha sido la adecuada; además, ha demostrado ser costo eficiente, sobre todo por ser un parámetro del hemograma más que una prueba adicional. El único problema, hasta el momento, es que solo está disponible en algunos autoanalizadores de hematología como los de las compañías Siemens y Sysmex, en sus modelos de cuarta generación, también conocidos como hemograma tipo VI o hemograma ampliado o extendido. Con el presente módulo se pretende presentar este nuevo parámetro que la comunidad médica debe incorporar como propio y los laboratorios clínicos deberían estar preparados para incorporarlo a sus portafolios de servicios, como una nueva herramienta complementaria en la prevención, la detección y el manejo de la eritropoyesis deficiente en hierro en sus diversas manifestaciones.&#x0D;

Erythropoiesis-stimulating agent hyporesponsiveness in end-stage renal disease patients.

Approximately 5-10% of patients with end-stage renal disease (ESRD) exhibit hyporesponsiveness to erythropoiesis-stimulating agents (ESAs), defined as a continued need for higher than 300 IU/kg/week doses of epoetin or a 1.5 mg/kg/week dose of darbepoetin. ESA hyporesponsiveness contributes to the morbidity, mortality and health-care economic burden of ESRD patients. The most common causes of ESA resistance are absolute or functional iron deficiency and inflammation. Maintaining adequate iron stores is clearly accepted as the most important strategy for reducing the ESA requirement and for enhancing ESA efficacy. Recent clinical studies have shown that iron administration to ESRD patients is associated with an increased risk of infection and atherosclerosis. ESA hyporesponsiveness due to chronic inflammation in ESRD patients has been reported to be improved by a number of interventions, including the use of biocompatible hemodialysis membranes, ultrapure dialysate, ascorbic acid therapy, vitamin E supplementation, and statin therapy. Other causes of ESA hyporesponsiveness include inadequate dialysis, hyperparathyroidism, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, primary bone marrow disorders, myelosuppressive agents, hemoglobinopathies, hemolysis, and hypersplenism. This article summarizes the common causes of ESA hyporesponsiveness and the proposed therapeutic interventions.

Evaluation of red cell and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease.

ObjectiveThe purpose of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency.MethodsPeripheral blood cells from 117 adult patients with anemia were classified according to iron status, and inflammatory activity, and the results of a hemoglobinopathy investigation as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β thalassemia (n = 25). The percentage of microcytic red cells, hypochromic red cells, and levels of hemoglobin content in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating between the different types of anemia.ResultsThere was no significant difference between the iron deficient group and anemia of chronic disease associated with absolute iron deficiency in respect to any parameter. The percentage of hypochromic red cells was the best parameter to discriminate anemia of chronic disease with and without absolute iron deficiency (area under curve = 0.785; 95% confidence interval: 0.661–0.909, with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic red cells minus hypochromic red cells was very accurate in differentiating iron deficiency anemia and heterozygous β thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005; with sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8).ConclusionThe indices related to red cells and reticulocytes have a moderate performance in identifying absolute iron deficiency in patients with anemia of chronic disease.

A prospective observational cohort study to identify the causes of anaemia and association with outcome in cardiac surgical patients

ObjectivesPreoperative anaemia is associated with increased morbidity and mortality. We sought to determine the relative frequencies of the different causes of anaemia including absolute and functional iron deficiency, and the...

High prevalence of iron deficiency in patients with acute decompensated heart failure.

Limited data are available on iron parameters in patients hospitalized for decompensation of chronic heart failure. Iron parameters of patients hospitalized for decompensation of chronic heart failure were prospectively assessed during the 72 h after hospital admission. Iron deficiency was defined according to the 2012 European Society of Cardiology Guidelines. Overall, 411 men (75 ± 12 years; 75% NYHA functional classes III/IV) and 421 women (81 ± 11 years; 71% NYHA classes III/IV) were evaluated. The prevalence of iron deficiency was 69% in men and 75% in women (including 41% and 49% with absolute iron deficiency, respectively). The prevalence of anaemia in men (<13 g/dL) was 68% and in women (<12 g/dL) it was 52%. Among non-anaemic patients, the prevalence of iron deficiency was 57% in men and 79% in women. Only 9% of patients received iron supplementation at the time of admission (oral, 9%; intravenous, 0.2%). Multivariate analysis showed that anaemia and antiplatelet treatment in men, and diabetes and low C-reactive protein in women, were independently associated with iron deficiency. Iron deficiency is very common in patients admitted for acute decompensated heart failure, even among non-anaemic patients. Given the benefit of iron therapy in chronic heart failure, our results emphasize the need to assess iron status not only in chronic heart failure patients, but even more so in those admitted for worsening heart failure, regardless of gender, heart failure severity, or haemoglobin level. Initiating iron therapy in hospitalized heart failure patients needs to be investigated.

Oral iron therapies in development for iron deficiency in chronic kidney disease

Iron supplementation remains a key component of anemia management in chronic kidney disease, which is associated with functional as well as absolute iron deficiency. There remains concern about the risks of intravenous iron, but oral iron supplements are poorly absorbed due to hepcidin-induced absorption block and are associated with gastrointestinal intolerance. Newer iron preparations with greater bioavailability and better tolerability than ferrous sulfate, or other agents which bypass the gastrointestinal block of iron absorption, offer the potential for normalizing iron stores without the need for intravenous iron. We review the current status of available iron supplements and summarize the recent clinical trial evidence for their use, with a particular focus on new oral supplements and those currently in development.

Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort.

BackgroundAnemia in later life is associated with increased morbidity and mortality. The purpose of this study was to evaluate the prevalence and possible causes of anemia in the elderly in a well defined hospital cohort.MethodsParticipants in this cross-sectional, retrospective analysis included all inpatients and outpatients aged ≥64 years with complete blood counts treated at Innsbruck Medical University Hospital between October 1, 2004 and September 29, 2005 (n=19,758, median age 73 years).ResultsAccording to World Health Organization criteria, 21.1% of these patients were anemic, ie, 30.7% and 37.0% at 80+ years and 90+ years, respectively. The prevalence of anemia was significantly correlated with advanced age (r=0.21; P<0.001) and male sex (P<0.001). In anemic patients, renal insufficiency with a glomerular filtration rate <30 mL/min/1.73 m2 (11.3% versus 2.1%), hyperinflammation (62.1% versus 31.4%), absolute (14.4% versus 6.9%) or functional (28.2% versus 11.8%) iron deficiency, and folate deficiency (6.7% versus 3.0%) were observed significantly more often than in nonanemic subjects (P<0.001). The pathogenesis of anemia was multifactorial, with decreased renal function (glomerular filtration rate <60 mL/min/1.73 m2), signs of inflammation, and functional iron deficiency detected in 11.4% of anemic patients. Hemoglobin was significantly correlated with elevated C-reactive protein (r= −0.296; P<0.001) and low transferrin saturation (r=0.313; P<0.001). Mean corpuscular volume correlated only weakly with the various anemia subtypes. Cytopenias and morphologic alterations suggestive of underlying myelodysplastic syndromes were found in a substantial proportion of anemic patients, including thrombocytopenia (5.4%), leukopenia (8.26%), and macrocytic alterations (18.4%).ConclusionAnemia was frequently diagnosed in this series of elderly patients. Partly treatable nutritional deficiencies, such as iron or folate deficiency, were identified as possible causes. A complex and heterogeneous interplay of chronic inflammation, functional iron deficiency, and renal impairment was identified in a large proportion of patients. A hitherto undiagnosed myelodysplastic syndrome can be assumed in a relevant proportion of patients. Morphologic classification based on mean corpuscular volume is inadequate from the standpoint of pathogenesis. New parameters are needed to differentiate the multifactorial pathogenesis of anemia in the elderly.

The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease.

The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1–5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8–28.7] to 36.1 ng/mL [14.1–92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) <20% and ferritin <40 ng/mL) had the lowest hepcidin levels (5.0 ng/mL [0.7–11.7]), and those with a normal iron profile (TSAT ≥20% and ferritin ≥40), the highest (34.5 ng/mL [23.7–51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin’s negative association with Hb level indicates that it is not down-regulated in CKD anemia.

Iron deficiency in chronic heart failure: from diagnosis to therapy

Anaemia and iron deficiency are frequent co-morbidities in patients with chronic heart failure. Both are bound to worsen an already reduced exercise capacity in these patients. Recent data have demonstrated that iron deficiency alone, i.e. without concomitant anaemia, reduces quality of life, exercise capacity and likely also survival. Two clinical entities should be differentiated in this context: absolute and functional iron deficiency, the first being an absolute deficiency of iron, the second representing a disturbed mobilisation capacity. The FAIR-HF study has shown that intravenous iron administration can improve quality of life and exercise capacity in affected patients. A correct diagnosis can easily be arrived at using parameters such as serum ferritin and transferrin saturation. Replenishing iron stores is most useful using the intravenous route, and administered doses need to be adjusted to individual needs.