Low Molecular Weight Iron Research Articles

Evidence for oxidative and not reductive stress in the aged rabbit heart.

Reductive stress, which is due to a paradoxical excess of antioxidants such as reduced glutathione (GSH) and GSH-related enzymes associated with decreased oxidant levels, has emerged as a pathogenetic mechanism of myocardial damage in pathological conditions such as protein aggregation cardiomyopathy. Notably, in the aged heart a cardiomyopathy-like pathology occurs leading to myocardial dysfunction. Whether reductive stress, or instead its counterpart oxidative stress, is operative in the aged mammalian heart needs to be elucidated also for the different therapeutic implications of such redox stress conditions. In the present investigation, we assessed GSH and the specific enzymatic activities of γ-glutamylcysteine synthetase (γ-GCS), glutathione reductase (GSSG-Red) and selenium-dependent glutathione peroxidase (GSH-Px) as endogenous antioxidants, together with oxidized glutathione (GSSG) and the glutathione redox ratio (GSH/GSSG), in the aerobically perfused hearts of aged rabbits (about 4.5years old) and young adult control rabbits (3-4months old). We also assessed in the aged and control hearts H2O2 and catalytically active low molecular weight iron (LMWI) as oxidant forces, as well as fluorescent damage products of lipid peroxidation (FDPL) and protein carbonyls (PC) as biomarkers of lipid and protein oxidation. Moreover, the effects of 4.5mM N-acetylcysteine (NAC) as reducing thiol antioxidant were studied on hemodynamic parameters and lipid peroxidation in the perfused hearts of the aged and control rabbits. The levels of GSH and of the GSH/GSSG ratio were lower, and those of GSSG higher, in the aged than in the control hearts. The aged hearts were also characterized by decreased activities of the antioxidant enzymes γ-GCS, GSSG-Red and GSH-Px, as well as by heightened levels of H2O2, LMWI, FDPL and PC, highlighting the occurrence of aging-dependent oxidative stress. Associated with such biochemical alterations, hemodynamic dysfunction occurred in the aged rabbit hearts, as evidenced by lowered developed pressure (DP) and enhanced end-diastolic pressure (EDP) with decreased coronary flow (CF). Remarkably, NAC administration significantly improved DP and EDP, and lowered lipid peroxidation, electively in the aged hearts. In conclusion, oxidative and not reductive stress is operative in the aged rabbit heart, whose hemodynamic dysfunction is improved by NAC together with reduction in myocardial lipid peroxidation.

Desideromastica: Tactile Chew Cravings in Iron Deficiency Anemia

Introduction: The compulsive craving and consumption of non-food substances, known as pica, is a well-documented symptom associated with iron deficiency anemia (IDA). Olfactory cravings associated with IDA are a recently described phenomenon known as desiderosmia. In our practice we observed a subset of patients with IDA who report specific tactile cravings associated with mastication. Methods: This study included patients from the Mayo Clinic (Rochester, MN) and Ankara Training and Research Hospital (Ankara, Turkey) Hematology practices who self-reported tactile mastication cravings during initial evaluation for IDA between 1/1/18 and 6/30/19. Information including sociodemographics, substance craved, values of hemoglobin (Hgb), mean corpuscular volume (MCV), and ferritin before and after iron replacement therapy, and symptom resolution after treatment were recorded. Results: We observed 12 patients with IDA who self-reported chew cravings during initial evaluation. All patients were female and the median age was 41.5 years (33-59). Of these 12 patients, median baseline Hgb, MCV, and ferritin were 9.4 g/dL (6.6-12.9), 73.7 fL (59.1-95.1), and 6 µg/L (2-21), respectively. Tactile cravings included chewing gum (3), mastic gum (2), ginseng (1), dry oats (1), crackers (1), pickles (1), chips (1), sawdust (1), and knitting rope (1). Many patients reported the frequency and satisfaction of these cravings resulted in jaw pain as well as the persistence of cravings despite this discomfort. Only 16.7% (2/12) reported concurrent ice pica. In total, 9 patients proceeded with observed treatment of their IDA with clinical follow-up and laboratory confirmation of iron repletion. Oral (ferrous glyconate or ferrous fumarate) and intravenous (ferric carboxymaltose, iron sucrose, or low molecular weight iron dextran) iron replacement were used in 33.3% (3/9) and 66.7% (6/9) patients, respectively. Post-treatment median laboratory values include: Hgb 12.7 g/dL (10.8-14.7), MCV 80.1 fL (76.1-91.7), and ferritin 98 µg/L (24-398). Overall, 88.9% (8/9) reported resolution of chew cravings after iron repletion. The lone patient with persistent symptoms had a baseline ferritin of 10 µg/L, improved to 398 µg/L after replacement, and settled back at 42 µg/L three months later. Discussion: Our patient experience provides suggestive evidence that oral tactile craving symptoms, distinct from ice pica, exists in a subset of patients suffering from IDA. For this, we propose the term "desideromastica" derived from the Latin words "desiderare" for desire and "mastica" for chew. "Desidero" can also be indicative of a reduction in iron, which relates to iron deficiency. Our hope in naming this relatively unexplored symptom associated with IDA will encourage additional clinicians to share their experience and guide future investigation. Disclosures No relevant conflicts of interest to declare.

Efficacy and Safety of Low Molecular Weight Iron Dextran (LMWID) Vs. Ferumoxytol in Treating Iron Deficiency Anemia

Introduction: Iron deficiency anemia is the most common form of anemia and hematologic problem worldwide. Treatment options include oral or intravenous (IV) iron replacement. Although oral iron is commonly employed as first-line therapy, many studies suggest that IV iron more effective and associated with better quality of life when compared to oral iron. Yet, adverse infusion reactions are possible. Several forms of IV iron are used in clinical practice, including low molecular weight iron dextran (LMWID), ferumoxytol, ferric gluconate, iron sucrose, and ferric carboxymaltose. We sought to compare the efficacy and safety of LMWID and ferumoxytol, the two most frequently used products at our center. Methods: A retrospective cohort analysis was conducted using internal pharmacy records. Adults with an ICD-10 diagnosis of iron deficiency anemia treated with LMWID or ferumoxytol from 2018 to 2019 were identified. Records were reviewed for demographics, comorbidities, allergies, type and frequency of iron administered. Outcomes of interest were comparisons of baseline and post-treatment hemoglobin [Hgb] and ferritin levels and adverse events (AEs) following infusion. Results: In total 55 patients received one of the two included iron preparations. Of the 40 cases of iron deficiency treated with LMWID, only 4 patients (10%) received a second dose. Of the first LMWID infusions (dose of 1000 mg), all patients demonstrated an increase in Hgb from a mean of 12.21 to 13.15 within an average of 2.75 months. Mean ferritin levels went from 28.34 pre-treatment to 231.14 post-treatment, within an average of 3.26 months. 2 patients (5%) received premedication, one with diphenhydramine or promethazine, based on prior history of an AE. AEs were documented in 3 patients (7.5%) and included arm swelling, dysphagia with globus sensation, and nausea. No patients received premedication prior to ferumoxytol infusion. Those receiving ferumoxytol demonstrated an increase in hemoglobin from a mean of 10.25 to 12.17 within an average of 4.2 months. Ferritin increased from baseline 75.93 to 150.33 within 3 months. AE of diarrhea and nausea were reported in only one patient (6.67%) upon second infusion of ferumoxytol. No patient in either group experienced AEs requiring hospitalization, nor did any patient develop severe hypersensitivity reactions, hypotension, or hypophosphatemia. Discussion: In our retrospective cohort, LMWID or ferumoxytol for treatment of iron deficiency were well tolerated with minimal AEs, limited to arm swelling, dysphagia and nausea in 3 patients. Those treated with ferumoxytol experienced similarly few AEs, with only one patient developing transient diarrhea and nausea. Hesitancy to utilize IV iron has persisted due to concerns for potential side effects including anaphylaxis. Our encouraging results provide additional evidence for the efficacy and safety of LMWID and furomoxytol, and should help to assuage fears that IV iron might be poorly tolerated or ineffective. Disclosures Shatzel: Aronora, Inc.: Consultancy.

Present and future of siderophore-based therapeutic and diagnostic approaches in infectious diseases.

Iron is an essential micronutrient required for the growth of almost all aerobic organisms; the iron uptake pathway in bacteria therefore represents a possible target for novel antimicrobials, including hybrids between antimicrobials and siderophores. Siderophores are low molecular weight iron chelators that bind to iron and are actively transported inside the cell through specific binding protein complexes. These binding protein complexes are present both in Gram negative bacteria, in their outer and inner membrane, and in Gram positive bacteria in their cytoplasmic membrane. Most bacteria have the ability to produce siderophores in order to survive in environments with limited concentrations of free iron, however some bacteria synthetize natural siderophore-antibiotic conjugates that exploit the siderophore-iron uptake pathway to deliver antibiotics into competing bacterial cells and gain a competitive advantage. This approach has been referred to as a Trojan Horse Strategy. To overcome the increasing global problem of antibiotic resistance in Gram negative bacteria, which often have reduced outer membrane permeability, siderophore-antibiotic hybrid conjugates have been synthetized in vitro. Cefiderocol is the first siderophore-antibiotic conjugate that progressed to late stage clinical development so far. In studies on murine models the iron-siderophore uptake pathway has been also exploited for diagnostic imaging of infectious diseases, in which labelled siderophores have been used as specific probes. The aim of this review is to describe the research progress in the field of siderophore-based therapeutic and diagnostic approaches in infectious diseases.

Donor Iron Deficiency Study (DIDS): protocol of a study to test whether iron deficiency in blood donors affects red blood cell recovery after transfusion.

Despite fulfilling all requirements for blood donation, a large proportion of regular blood donors are iron deficient. Red blood cells (RBC) from iron-deficient donors may be particularly susceptible to damage induced by standard refrigerated storage. Herein, we present a study protocol for testing whether correcting iron deficiency in donors with iron-deficient erythropoiesis will improve the quality of their refrigerator-stored RBC. This is a randomised, controlled, double-blind clinical trial. Sixty healthy regular donors who meet donation standards, while exhibiting iron-deficient erythropoiesis by laboratory testing criteria, will donate a single standard RBC unit that will be leucoreduced and stored in a refrigerator under standard conditions for 40-42 days. A 51Cr-radiolabelled 24-hour RBC recovery study will be performed and then these donors will be randomised to receive, in a double-blinded fashion, either intravenous saline, as a control, or low-molecular weight iron dextran (1 g), to provide total iron repletion. Four to six months later, they will donate a second RBC unit, which will be similarly stored, and autologous 51Cr-labelled 24-hour post-transfusion RBC recovery will again be determined. The primary endpoint will be the change in 24-hour post-transfusion recovery from the first to the second donation. The primary outcome will be the group mean difference in the primary endpoints between the group receiving intravenous saline and the group receiving intravenous iron dextran. Secondary outcomes will be quality of life, fatigue, and emotional health, assessed by surveys. This study will provide definitive evidence as to whether donor iron deficiency affects the quality of the blood supply and will assess the severity of symptoms affecting iron-deficient blood donors.

Therapeutic Macromolecular Iron Chelators.

Iron is a key element for every single living process. On a fundamental level, targeting iron is a valuable approach for the treatment of disorders caused by iron overload. Utilizing iron chelators as therapeutic agents has received expanding consideration in chelation therapy. Approved low molecular weight (MW) iron chelators to treat iron overload may experience short half-lives and toxicities prompting moderately high adverse effects. In recent years, polymeric/macromolecular iron chelators have received attention as therapeutic agents. Polymeric iron chelators show unique pharmaceutical properties that are different to their conventional small molecule counterparts. These polymeric iron chelators possess longer plasma half-lives and reduced toxicities, thus exhibiting a significant supplement to currently using low MW iron chelator therapy. In this review, we have briefly discussed polymeric iron chelators and factors to be considered when designing clinically valuable iron chelators. We have also discussed applications of polymeric iron chelators in the diseases caused by iron overload associated with transfusional hemosiderosis, neurodegenerative disorders, malaria and cancer. With this, research findings for new polymeric iron chelators are also covered.

Screening and characterization of siderophore producing endophytic bacteria from Cicer arietinum and Pisum sativum plants

Siderophores are low molecular weight iron chelating secondary metabolites synthesized by various groups of microorganisms help in scavenging iron-limited conditions. Siderophores produced by endophytic bacteria facilitate the plant growth by providing iron to plants. The objective of this study was to isolate and screen the siderophore producing endophytes from nodules and roots of Cicer arietinum and Pisum sativum plants. Out of total eighty four isolates, only 14 endophytes produced siderophore and quantitative analysis was also done. Ten best siderophore producers (above 65% siderophore units) were characterized for the type of siderophore produced. Most of them were producing hydroxamate and carboxylate type of siderophores. These ten isolates were evaluated for other plant growth promoting (PGP) traits invitro. All of them were producing ammonia and IAA. Isolate CPFR10 was found to be positive for all the PGP traits viz. ammonia, organic acid, HCN and IAA production. Diversity analysis of these ten isolates using ARDRA (Amplified rDNA Restriction Analysis) profile revealed nine haplogroups at 90% similarity.

RETRACTED ARTICLE: Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial

We, the Editor and Publisher of the Journal of Maternal-Fetal and Neonatal Medicine, have retracted the following article: A. M. Darwish, H. A. Fouly, W. H. Saied & E. Farah (2019) Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial, The Journal of Maternal-Fetal & Neonatal Medicine, 32:13, 2214–2220, DOI: 10.1080/14767058.2018.1429396. Since publication, significant concerns have been raised about the integrity of the data and the reported results in the article. Concerns have also been raised about unexplained overlap between this article and another study published previously (online in 2017) by the same corresponding author: A. M. Darwish, E. E. Khalifa, E. Rashad & E. Farghally (2019) Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial, The Journal of Maternal-Fetal & Neonatal Medicine, 32:3, 398–403, DOI: 10.1080/14767058.2017.1379988. Specifically, these two studies contain 27 identical values in the baseline table and 38 identical values in the outcome tables. Upon query, the authors have not provided responses to our concerns or supplied their original data for review. As significant concerns about the integrity of the article remain, we are therefore retracting the article. The authors have been notified of the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Iron status and oxidative stress in the aged rabbit heart

Altered iron status may be relevant to the pathophysiology of aging. We have assessed redox-active catalytic low molecular weight iron (LMWI), non-heme iron (NHI), heme iron (HI), and total iron (TI) in the aerobically perfused hearts of aged rabbits (AR, about 4.5years old) and young adult control rabbits (YACR, 3–4months old); myocardial lipid and protein oxidations were also assessed as oxidative stress biomarkers. The levels of LMWI and NHI, as well as of lipid and protein oxidation, were higher, while HI content was lower, in the hearts of AR than in those of YACR; TI did not differ significantly between the two groups. Together with these findings, hemodynamic dysfunction, namely heightened end-diastolic pressure (EDP) and lowered coronary flow (CF), occurred in the AR hearts. Notably, such pattern of hemodynamic dysfunction associated with myocardial oxidant damage occurred in the hearts of other YACR perfused in the presence of a cell-permeable form of iron, i.e., the iron/hydroxyquinoline complex, pointing to the involvement of catalytic iron in the aged heart damage. Moreover, as shown in other AR, heart perfusion in the presence of the iron chelator deferoxamine (0.6mM or 3.6mM) reduced the myocardial levels of LMWI, without significantly affecting those of NHI, HI, and TI; concomitantly, in AR deferoxamine lowered myocardial lipid and protein oxidation, and reduced EDP with a tendency to augment CF. Instead, deferoxamine, even at high concentration of 3.6mM, had no significant effects in the YACR. In conclusion, altered iron status with catalytic LMWI burden occurs in the aged rabbit heart, eventually resulting in iron-dependent cardiac oxidative stress and hemodynamic dysfunction.

Intravenous iron treatments for iron deficiency anemia in inflammatory bowel disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK

ABSTRACTIntroduction: Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD.Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data.Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial

Study objective: To test safety, efficacy, and cost-effectiveness of total dose infusion (TDI) of low molecular weight (LMW) iron dextran for treatment of iron deficiency anemia (IDA) during pregnancy in comparison to oral ferrous fumarate.Design: Prospective interventional randomized controlled trial (RCT). Design classification. Canadian Task Force II3.Setting: Antenatal clinic and causality unit of a tertiary care referral facility and University Hospital.Patients: A total 66 anemic pregnant women (hemoglobin level between 7–10 g/dl).Intervention: Administration of a LMW iron dextran as a TDI (group A) or Oral iron ferrous fumarate 60 mg elemental iron three times daily (group B) followed by remeasurement of hemoglobin after 4 weeks.Measures and main results: The main outcome measure was clinical and laboratory improvement of anemia after 4 weeks of starting the therapy. Both groups showed a significant clinical improvement of anemia 4 weeks post-therapy. However, the first improvement of symptoms was significantly faster in group A. Complete blood count (CBC) as well as all iron indices were improved in both groups after 4 weeks of therapy, but were significantly better in group A than B. Side effects in group B were mainly gastrointestinal (GIT) while one case of mild hypersensitivity to TDI and another one case of local reaction at the site of injection were reported in group A.Conclusions: It is concluded that despite being equally effective in improving both clinical and laboratory evidence of IDA, TDI allows iron restoration with a single dose faster than oral iron therapy with a reasonable safety profile. It is a good example of office one-stop therapy. Nevertheless, noninvasive selfusage at home is a clear advantage of the cheaper oral iron therapy which makes it the first choice for treating IDA in the second and third trimesters of pregnancy in tolerable cases.Trial registration: ClinicalTrials.gov identifier: NCT03212781.

Intravenous Iron Treatments For Iron Deficiency Anemia In Inflammatory Bowel Disease: A Budget Impact Analysis Of Iron Isomaltoside 1000 In The UK

Iron deficiency (ID) is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron should be considered the first-line iron-correction treatment in patients with clinically active IBD, hemoglobin <10g/dL, previous oral iron intolerance, or requiring erythropoiesis-stimulating agents. The study objective was to evaluate resource use and costs associated with using iron isomaltoside (Monofer; IIM) relative to other intravenous iron formulations in patients with iron deficiency anemia (IDA) associated with IBD. A budget impact model was developed to evaluate the cost of IIM relative to ferric carboxymaltose (Ferinject; FCM), low molecular weight iron dextran (Cosmofer; LMWID) and iron sucrose (Venofer; IS). Iron deficits were modeled using dosing tables and the need for retreatments was modeled using a pooled retrospective analysis of randomized trial data. The analysis was conducted over 5 years in patients with mean bodyweight of 75.4 kg (SD 17.4 kg) and hemoglobin levels of 10.8 g/dL (SD 1.4 g/dL) based on observational data from patients with IBD. Costs were modeled using healthcare resource groups. Using IIM required 1.29 infusions (per treatment) to correct the mean iron deficit, compared with 1.64, 1.29 and 7.14 with FCM, LMWID and IS, respectively. Patients using IIM required multiple infusions in 28.7% of cases, compared with, 64.3%, 28.7% and 100% with FCM, LMWID and IS, respectively. Total costs were estimated to be GBP 2,593 per patient with IIM or LMWID, relative to GBP 3,309 with FCM (savings of GBP 717 with IIM) or GBP 14,382 with IS (savings of GBP 11,789 with IIM). Using IIM in place of FCM or IS markedly reduced the number of infusions required to correct ID in patients with IBD and IDA. The reduction in infusions was accompanied by substantial reductions in cost relative to FCM and IS.

Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds.

Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control). Rats treated with LMWID, FMX, or IIM showed significant changes in most measures of oxidative/nitrosative stress, inflammation, and iron deposition compared to the saline-treated controls, with greatest changes in the LMWID treatment group. Increases in products of lipid peroxidation (thiobarbituric acid reactive substances) and protein nitrosation (nitrotyrosine) were consistent with increases in the activity of antioxidant enzymes (catalase, Cu,Zn-SOD, GPx), decreases in antioxidative capacity (reduced:oxidized GSH ratio), increased levels of transcription factors involved in the inflammatory pathway (NF-κB, HIF-1α), inflammatory cytokines (TNF-α, IL-6), adhesion molecules (VCAM-1), markers of macrophage infiltration (ED-1), and iron deposition (Prussian blue, ferritin). Since changes in measured parameters in FCM- or IS-treated rats were generally modest, the results suggest that FCM and IS have a low propensity to induce lung inflammation. The relevance of these findings to clinical safety profiles of the tested intravenous iron products requires further investigation.

A budget impact analysis of parenteral iron treatments for iron deficiency anemia in the UK: reduced resource utilization with iron isomaltoside 1000.

Background and aimsThe reported prevalence of iron deficiency anemia (IDA) varies widely but estimates suggest that 3% of men and 8% of women have IDA in the UK. Parenteral iron is indicated for patients intolerant or unresponsive to oral iron or requiring rapid iron replenishment. This study evaluated differences in the cost of treating these patients with iron isomaltoside (Monofer®, IIM) relative to other intravenous iron formulations.MethodsA budget impact model was developed to evaluate the cost of using IIM relative to ferric carboxymaltose (Ferinject®, FCM), low molecular weight iron dextran (Cosmofer®, LMWID), and iron sucrose (Venofer®, IS) in patients with IDA. To establish iron need, iron deficits were modeled using a simplified dosing table. The base case analysis was conducted over 1 year in patients with IDA with mean bodyweight of 82.4 kg (SD 22.5 kg) and hemoglobin levels of 9.99 g/dL (SD 1.03 g/dL) based on an analysis of patient characteristics in IDA trials. Costs were modeled using UK health care resource groups.ResultsUsing IIM required 1.3 infusions to correct the mean iron deficit, compared with 1.3, 1.8, and 7.7 with LMWID, FCM, and IS, respectively. Patients using IIM required multiple infusions in 35% of cases, compared with 35%, 77%, and 100% of patients with LMWID, FCM, and IS, respectively. Total costs were estimated to be GBP 451 per patient with IIM or LMWID, relative to GBP 594 with FCM (a GBP 143 or 24% saving with IIM) or GBP 2,600 with IS (a GBP 2,149 or 83% saving with IIM).ConclusionUsing IIM or LMWID in place of FCM or IS resulted in a marked reduction in the number of infusions required to correct iron deficits in patients with IDA. The reduction in infusions was accompanied by substantial reductions in cost relative to FCM and IS over 1 year.

Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting

Practitioners often avoid administering iron dextran in parenteral nutrition (PN) for hospitalised children because of the concern for anaphylaxis. The primary aim of the present study was to determine the risk of anaphylaxis associated with exposure to PN containing iron dextran in the inpatient setting. Charts were reviewed for all children admitted to The Children's Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received PN containing low molecular weight (LMW) iron dextran. Subject characteristics, primary diagnoses and PN orders were evaluated. The pharmacy adverse events database was queried for adverse drug reactions. Over three years, 89 subjects received PN containing a maintenance dose of LMW iron dextran with a total of 2774 days of exposure. Subjects ranged from two months to 21 years of age and received between 1 and 196 days of PN containing iron dextran. The mean dose of iron dextran in children decreased as the weight category increased from <5 kg (0.21 ± 0.05 mg/kg/day) to ≥40 kg (1.9 ± 0.5 mg/day; P-value for trend <0.005). No anaphylactic reactions occurred in any subjects. PN containing a maintenance dose of LMW iron dextran can be safely administered to hospitalised children, and further studies are need to evaluate the potential to prevent iron deficiency anaemia and the need for additional IV iron infusions.

The available intravenous iron formulations: History, efficacy, and toxicology.

A number of intravenous iron formulations have been developed over the past 65 years which rely on dextran or other compounds to prevent uncontrolled release of free iron to the circulation. High molecular weight dextran was associated with a number of serious adverse reactions and was removed from markets worldwide in 2009. The preponderance of published evidence suggests that the formulations of parenteral iron currently available in the United States, including low molecular weight iron dextran, are all safe and effective and there are no major, clinically important differences among them in terms of either efficacy or safety. For patients with chemotherapy induced anemia or with anemia of end stage renal disease who are being treated with hemodialysis, it is reasonable to use any of the iron formulations, including iron sucrose and ferric gluconate, as frequent patient encounters with health caregivers are a routine part of care and the need to administer multiple low doses of IV iron is not a major disadvantage. However, a single infusion of a total iron dose is as effective and safe when giving iron preparations containing low molecular weight iron dextran, ferumoxytol, iron isomaltoside, or ferric carboxymaltose. Use of a single total dose infusion results in a decreased number of intravenous infusions with a lower cumulative risk for infusion reactions or extravasations, a reduced need for multiple office visits and repeated utilization of medical staff, and increased convenience for physicians and patients.

Iron deficiency: a new alternative when oral iron fails

Iron deficiency is the most common nutritional deficiency worldwide. The estimated prevalence in the US is about 7% among preschool-aged children and 10%-20% among adolescent females. Although most patients will not develop overt anemia, even mild deficiency may cause acute symptoms and result in long-term cognitive defects, underscoring the importance of effective treatment. In theory, correction of iron deficiency is simple: deliver sufficient amounts of bio-available iron to the duodenum and upper jejunum and let nature takes its course. In practice, therapeutic doses of oral iron often are accompanied by unpleasant gastrointestinal symptoms, and the formulations suitable for young children are all unpalatable to some degree. Thus, compliance with oral iron is often poor, and even excellent compliance may be inadequate for individuals with malabsorption or ongoing blood loss. The original parenteral iron formulation, high molecular weight iron dextran, is no longer available in the US due to its relatively high incidence of hypersensitivity reactions. Although low-molecular weight iron dextran is less likely to cause such reactions, test doses and careful monitoring for anaphylaxis are still recommended. Two newer parenteral formulations, iron sucrose and sodium ferric gluconate, are considered relatively safe and are approved for both adults and children, but typically require multiple doses to achieve adequate iron replacement. A newer iron formulation, ferric carboxymaltose, requires no test dose and the recommended infusion time is only 15 minutes. Although not yet approved for pediatric use, it is approved in both Europe and the US for adults “who have intolerance to oral iron or have had unsatisfactory response to oral iron.” In this volume of The Journal, Powers et al report their experience using ferric carboxymaltose in 72 children and adolescents with iron deficiency anemia. Mild, transient side effects were experienced by only 16% of patients, and almost one-half of the subjects required only a single infusion; all but one patient demonstrated improved hematologic values, with two-thirds showing a complete hematologic response. Although expensive compared with other parenteral formulations—all of which, in turn, are much more expensive than oral iron—its convenience and safety profile may make it an attractive option for many patients in whom oral iron therapy is not feasible. Article page 212 ▶ Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral IronThe Journal of PediatricsVol. 180PreviewTo assess the benefits and risks of intravenous (IV) ferric carboxymaltose (FCM) in children with iron deficiency anemia (IDA). Full-Text PDF

A novel approach to quantify different iron forms in ex-vivo human brain tissue.

We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40–50 nm, which is not compatible with the ferritin protein, the core of which is typically 6–8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

CARDIAC DISORDER IN HEMODIALYSIS: BENEFITS OF CHINESE HERBS

Background:A major cause of mortality in hemodialysis patients is cardiac disease. Most complementary and alternative therapies, including Chinese herbal medicine, have been useful in the treatment of cardiac disorders.Materials and Methods:A 46 year old Asian woman with chronic renal failure was admitted to the clinic for hemodialysis. In the course of the fifth session of standard dialysis, she developed shock followed by a ventricular tachycardia which rapidly degenerated into cardiac arrest, from which she was resuscitated through cardio-pulmonary resuscitation. The following therapeutic strategies were applied: low discharge oxygen inhalation; stricter water and salt restriction; dialysate temperature set at 36.0 °C; rhEPO 3000u, per week, low molecular weight iron dextran, 200mg/day, intravenously for five days; the patient received Chinese herbal concoction orally.Results:The patient obtained efficient standard dialysis without any cardiac syndrome.Conclusion:Chinese herbs are useful in the management of cardiac disorders in hemodialysis. Chinese herbs may provide more benefits by adjusting dialysis strategies.

Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density.

Desferrioxamine (DFO) is a clinically approved, high affinity iron chelator used for the treatment of iron overload. Due to its short half-life and toxicity, DFO is administered for 8-12 h per day, 5-7 d per week. In this manuscript, the influence of molecular properties of hyperbranched polyglycerol (HPG)-DFO conjugates on their iron binding by isothermal titration calorimetry, iron removal efficiency from ferritin in presence and absence of a low molecular weight (MW) iron chelator, and protection against iron mediated oxidation of proteins is reported. The iron binding properties of HPG-DFO are slightly altered with size and DFO density of conjugates. The lower MW conjugate shows greater iron removal efficiency at room temperature, however, the efficacy of high MW conjugates increases at physiological temperature. The iron removal from ferritin by HPG-DFO conjugates increases significantly in presence of a low MW chelator, suggesting the potential of combination therapy. The molecular properties of the polymer scaffold also have influence on the prevention of iron mediated oxidation of proteins by the conjugates. The results therefore help to define the iron binding thermodynamics of HPG-DFO and their dependence on MW, and can be extended to improve the general understanding of polymeric chelator-iron interactions in situ.