Parenteral iron therapy in children with iron deficiency anemia

Iron deficiency anemia(IDA)continues to be a global public health problem.Oral iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral formulations.In subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is indicated.Despite numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very limited.Although mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron formulations.In this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

Carbon Monoxide Modulates Auxin Transport and Nitric Oxide Signaling in Plants under Iron Deficiency Stress

Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.

Role of iron deficiency anemia in inflammatory bowel disease

Inflammatory bowel disease(IBD)is a relapsing chronic inflammatory disorder of the small and large gut with rising incidence and prevalence worldwide.Iron deficiency anemia is one of the most common extraintestinal manifestations of IBD,which correlates with the disease activity and tendency to relapse even after successful management.Anemia affects various aspects of quality of life,such as physical,cognitive,emotional,and workability,as well as healthcare costs.The anemia in IBD can be due to iron deficiency(ID)or chronic disease.The relative frequency of ID in IBD is 60%,according to some studies,and only 14%receive treatment.The evaluation of ID is also tricky as ferritin,being an inflammatory marker,also rises in chronic inflammatory diseases like IBD.The review of anemia in IBD patients involves other investigations like transferrin saturation and exploration of other nutritional deficiencies to curb the marker asthenia with which these patients often present.It underscores the importance of timely investigation and treatment to prevent long-term sequelae.We can start oral iron therapy in certain circumstances.Still,as inflammation of the gut hampers iron absorption,an alternative route to bypass the inflamed gut is usually recommended to avoid the requirement for blood transfusions.

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Physical Performance of Migrant Schoolchildren with Marginal and Severe Iron Deficiency in the Suburbs of Beijing

Objectives To investigate relationship between iron deficiency of different degrees and physical performance and habitual activity of migrant schoolchildren at the age of 11-14 years. Methods Ninety one randomly selected schoolchildren were divided into three groups according to their iron status. Iron status including hemoglobin （Hb）, serum ferritin （SF）, serum iron （SI） and sTfR was determined. Physical performance tests included maximum oxygen consumption （VO2max） and maximum work time. Energy expenditure （EE） and daily physical activity were estimated by recording 24-h heart rate （HR）. Dietary intake was assessed with frequency questionnaires, and physical activity level was estimated with frequency and physical activity questionnaires. Results Severe iron deficiency （IDA） impaired the aerobic capacity and habitual physical activity. When fat-free mass （FFM） was considered, VO2max （VO2max/FFM） was significantly lower in the iron-marginal group than in the iron-adequate groups among girls （P=0.02）, but such a deference was not found among boys （P=0.28）. Aerobic activity and EE at leisure were significantly lower in the severe iron deficient group than in the marginal iron deficient and iron adequate groups. Net HR at leisure time was correlated with lib, log SF, body weight, and FFM （P〈0.05）. Conclusion The functional effect of iron deficiency on physical performance and habitual physical activity rely on the degree of current iron deficiency. Severe iron deficiency significantly impairs both aerobic capacity and habitual physical activity. Iron-marginal deficiency impairs VO2max/FFM in girls, rather than in boys.

Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral iron preparations are efficacious but poorly tolerated due to non-absorbed iron-mediated GI side effects. However, oral iron dose may be reduced with no effect on its efficacy while decreasing side effects and patient discontinuation rates. Parenteral iron therapy replenishes iron stores quicker and is better tolerated than oral therapy. Serious hypersensitive reactions are very rare with new intravenous preparations. While data on worsening of inflammatory bowel disease (IBD) activity by oral iron therapy are not conclusive, parenteral iron therapy still seems to be advantageous in the treatment of IDA in patients with IBD, because oral iron may not be sufficient to overcome the chronic blood loss and GI side effects of oral iron which may mimic IBD exacerbation. Finally, we believe the choice of oral vs parenteral iron therapy in patients with IBD should primarily depend on acuity and severity of patients’ signs and symptoms.

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by

Role of small bowel capsule endoscopy in the diagnosis and management of iron deficiency anemia in elderly: A comprehensive review of the current literature

Iron deficiency anemia(IDA)is common and often under recognized problem in the elderly.It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract.Twenty percent of elderly patients with IDA have a negative upper and lower endoscopy and two-thirds of these have a lesion in the small bowel(SB).Capsule endoscopy(CE)provides direct visualization of entire SB mucosa,which was not possible before.It is superior to push enteroscopy,enteroclysis and barium radiography for diagnosing clinically significant SB pathology resulting in IDA.Angioectasia is one of the commonest lesions seen on the CE in elderly with IDA.The diagnostic yield of CE for IDA progressively increases with advancing age,and is highest among patients over 85 years of age.Balloon assisted enteroscopy is used to treat the lesions seen on CE.CE has some limitations mainly lack of therapeutic capability,inability to provide precise location of the lesion and false positive results.Overall CE is a very safe and effective procedure for the evaluation of IDA in elderly.

Anemia and iron deficiency in gastrointestinal and liver conditions

Iron deficiency anemia(IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

Effects of H pylori therapy on erythrocytic and iron parameters in iron deficiency anemia patients with H pylori-positive chronic gastristis

AIM： To elucidate the influences of Hpylori infection on oral iron treatment for iron deficiency anemia （IDA）.METHODS： A total of 86 patients were divided into two groups： group A, receiving ferrous succinate combined with triple therapy for H pylori eradication, and group B （control）, treated with ferrous succinate only. During treatment of IDA, dynamic changes in hemoglobin （Hb） level, mean corpuscular volume （MCV）, mean corpuscular hemoglobin （MCH）, serum iron （SI）, and serum ferritin （SF） were compared between the groups.RESULTS： Hb was slightly higher in group A at d 14 alter the start of triple therapy for H pylori eradication （P 〉 0.05）. After the therapy, the increase of Hb in group A became significantly faster than that in group B （P 〈 0.05）. At d 56, the mean Hb in group A returned to the normal level, however, in group B, it was lower than that in group A （P 〈 0.05） although it had also increased compared with that before oral iron treatment. The MCV and MCH in group A recovered to the normal level, and were much higher than those in group B （P 〈 0.05） at d 21. In Group B, the MCV and MCH remained at lower than normal levels until d 42 alter the start of therapy. And then, they reached a plateau in both groups and the differences disappeared （P 〉 0.05）. The SF in group A was higher than that in group B （P 〈 0.05） 28 d alter the treatment and its improvement was quicker in group A （P 〈 0.05）, and the difference between the two groups was even more significant （P 〈 0.01） at d 56. The SI in group A was higher than that in group B （P 〈 0.05） at d 14 and this persisted until d 56 when the follow-up of this research was finished.CONCLUSION： Treatment of H pylori can enhance the efficacy of ferrous succinate therapy in IDA patients with Hpylori-positive chronic gastritis.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure

Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.

Efficacy of Different Iron Fortificants in Wheat Flour in Controlling Iron Deficiency

Objective To observe the different impacts of electrolytic iron, FeSO4, and NaFeEDTA on body iron store of anemic school students. Methods Four hundreds anemic students at the age of 11-18 years were divided into four groups. Of which, three consumed different iron fortificants from wheat flour as food vehicle for six months and one consumed non-fortified flour （control）. The fortification level of electrolytic iron, FeSO4, and NaFeEDTA was 60 mg Fe/kg, 30 mg Fe/kg, and 20 mg Fe/kg, respectively. Blood samples were collected at 0, 2, 4, and 6 months and hemoglobin （Hb）, serum ferritin （SF）, and transferrin receptor （TfR） were measured. Results The hemoglobin levels in three intervention groups increased, the increments of Hb in the NaFeEDTA group were significantly higher than that in the other groups. SF and TfR levels increased in the tested groups and body iron store in the NaFeEDTA group was higher than that in the other groups. These parameters did not show any significant changes in the control group. Conclusion NaFeEDTA and FeSO4 tortified wheat flour has positive impacts on iron status in anemic students and NaFeEDTA is more effective than FeSO4, while electrolytic iron is less effective in improving iron store in anemic students.

A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases:A pilot study

AIM： To investigate the effect of a new oral preparation, highly concentrated in fish cartilage, in a group of inflammatory bowel diseases （IBD） patients with chronic iron deficient anemia. METHODS： In an open label pilot study, we supplemented a group of 25 patients （11 with Crohn＇s disease and 14 with ulcerative colitis） in stable clinical conditions and chronic anemia with a food supplement which does not contain iron but contains a standardized fraction of fish cartilage glycosaminoglycans and a mixture of antioxidants （Captafer Medestea, Turin, Italy）. Patients received 500 mg, twice a day during meals, for at least 4 mo. Patients were suggested to maintain their alimentary habit. At time 0 and after 2 and 4 too, emocrome, sideremia and ferritin were examined. Paired data were analyzed with Student＇s t test. RESULTS： Three patients relapsed during the study （2 in the 3^rd too, 1 in the 4^th too）, two patients were lost to follow up and two patients dropped out （1 for orticaria, 1 for gastric burning）. Of the remaining 18 patients, levels of serum iron started to rapidly increase within the 2^nd mo of treatment, P 〈 0.05）, whereas serum ferritin and hemoglobin needed a longer period to significantly improve their serum levels （too 4） P 〈 0.05. The product was safe, easy to administer and well tolerated by patients. CONCLUSION： These data suggest a potential new treatment for IBD patients with iron deficiency chronic anemia and warrant further larger controlled studies.

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin

AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

A New Concept in the Control of Iron Deficiency:Community-based Preventive Supplementation of At-Risk Groups by the Weekly Intake of Iron Supplements

Iron deficiency (ID), defined as an insufficient supply of iron to the cells of the body after iron reserves have been exhausted, is the most prevalent single nutritional deficiency, affecting over 2, 000 million people, mostly in the developing world. Infants, small children, adolescents and pregnant and fertile-age women are most vulnerable. Only about 50 % of people with ID develop iron deficiency anemia (IDA), since this is a late manifes tation of chronic ID. Based on the average daily iron requirement and on the rate of iron reutilization from red cell hemoglobin destruction, it can be estimated that after iron stores have been depleted, it takes about 4 months of ID erythropoiesis for adult women to have a drop in hemoglobin concentration [Hb] of 10 g/l, if the iron intake is only 70 % of requirement. IDA can be defined by a [Hb] below an appropriate cut-off point for age,sex, physiological condition and altitude above sea level, or by a [Hb] increment of morethan 10 g/l to the administration of adequate doses of iron. More than 85 % of the nutritional anemias are IDA alone, or of iron combined with folate or other nutrient deficiencies [WHO/UNICEF/UNU, 1997; Yip, 1994].

Autoimmune gastritis presenting as iron deficiency anemia in childhood

AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.

γ⁃Fe2O3@carboxymethyl Cellulose as Potential Oral Nanomedicine for Iron Deficiency Anemia Treatment on Rats

Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia(IDA)due to the convenience of large dose administration and good patient compliance.However,the gastrointestinal adverse impact caused by Fe2+stimulus and low bioavailability severely impedes its therapeutic effects.In recent years,it has been found that nano iron⁃based nanoparticles with high surface⁃to⁃volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance.For further clinical development,nano materials need to meet the pharmaceutical quality demand.Carboxymethyl cellulose(CMC)is a significant pharmaceutical ingredient applied in approved drug formulations,and polyglucosorbitol carboxymethylether(PSC)has been utilized in iron⁃based nanomedicine ferumoxytol synthesis,both of which can be firmly anchored on iron oxide by carboxyl chelation.In this work,iron oxide nanoparticles(NPs)modified with CMC were designed and synthesized,and the structure composition and physicochemical properties were distinctly characterized.Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC.Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety.The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.

Paraesophageal hernia and iron deficiency anemia:Mechanisms,diagnostics and therapy

There is ample clinical evidence suggesting that the presence of large axial or paraesophageal hernias may lead to iron deficiency anemia.So-called Cameron lesions,as well as other small mucosa erosions,in the sliding area of these diaphragmatic hernias lead to invisible chronic blood loss and consequently to iron depletion.While the spectrum of symptoms in these patients is large,anemia is often not the only indication and typically not the primary indication for surgical correction of diaphragmatic hernias.Drug treatment with proton pump inhibitors and iron substitution can alleviate anemia,but this is not always successful.To exclude other possible bleeding sources in the gastrointestinal tract,a comprehensive diagnostic program is necessary and reviewed in this manuscript.Additionally,we discuss controversies in the surgical management of paraesophageal hernias.

Effect of Iron Deficiency on Heterocyst Differentiation and Physiology of the Filamentous Cyanobacterium Anabaena sp. PCC 7120

The effect of iron deficiency on heterocyst differentiation and some physiological properties of the filamentous cyanobacterium Anabaena sp. PCC 7120 was investigated. Under moderate iron limitation conditions, achieved by addition of iron chelator 2,2′\|Dipyridyl (<80 μmol/L) led to delayed heterocyst differentiation, no heterocyst differentiation was observed under severe iron limitation conditions, when the concentration of 2,2′\|Dipyridyl in the medium was more than 100 μmol/L . It seemed that there are certain iron\|regulated genes or operons whose function is to control heterocyst development. In addition, iron deficiency impaired the growth. Low\|iron cells had a decrease in the quantities of pigment content (chlorophyll and phycocyanin content),the whole cell in vivo absorbance spectra confirmed the decrease, the protein electrophoretic profiles revealed that iron\|deficient cells had less protein bands, with the increase of 2,2′\|Dipyridyl ,the protein bands was more and more less. And differently, iron deficiency also caused an increase of ROS (Reactive Oxygen Species)and SOD activity, it suggests that iron deficiency led to oxidative stress, which generally occured under high\|iron conditions.

Flammulina velutipes polysaccharide-iron (Ⅲ) complex used to treat iron deficiency anemia after being absorbed via GLUT2 and SGLT1 transporters

Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex(FVP1-Fe(Ⅲ))in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(Ⅲ)was mediated by sodium-dependent glucose transporter-1(SGLT1)and facilitated glucose transporter-2(GLUT2)and GLUT2 played a dominant function. The multidrug resistance-associated protein-2(MRP-2)was involved in the efflux of FVP1-Fe(Ⅲ)across the Caco-2 cells. In vivo, FVP1-Fe(Ⅲ)had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO_4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(Ⅲ)could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C(vit C)could enhance the therapeutic effect of FVP1-Fe(Ⅲ). These present findings showed that FVP1-Fe(Ⅲ)could be exploited as a novel iron supplement to treat IDA.