Estimation of iron deficiency anemia in Iranian children and adolescents: a systematic review and meta-analysis

Objectives: Iron deficiency anemia (IDA) is a major health issue in those aged less than 18 years old with high impact on their development. There are several reports from Iran with variable results. Systematic review and met analysis of these data would reveal a more realistic view of the prevalence of iron deficiency (ID).

Methods: We conducted a systematic search of national and international databases from December 1990 to 31 January 2016 for population-based studies providing estimates on the prevalence of IDA in Iran. From the extracted crude prevalence rates, the heterogenic index of the studies was determined using the Cochran's test (Q) and I₂. Then, based on the heterogenetic results, a random effects model for estimate pooled prevalence of IDA was used. Meta-regression was applied to determine heterogeneity suspected factors.

Results: The overall prevalence of IDA in Iranian population with age less than 18 years was estimated to be 13.9% (95% CI: 10.8–17.1) and the overall prevalence of ID was 26.9% (95% CI: 19.7–34.1). The prevalence of IDA was 7.9% (95% CI: 4.1–11.7) in males and 8.5% (95% CI: 6.1–10.8) among females aged under than 18 years.

Discussion: Despite the efforts of ministry of health and medical education of Iran in implementing free iron supplements for infants and for girls, the prevalence of ID and resultant anemia is considerable. Further interventions to increase use of supplements when they are provided and special programs for non-covered groups including boys under six are in great need.     

Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double‐blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate‐to‐severe HSRs, including anaphylaxis, or moderate‐to‐severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate‐to‐severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least‐squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.     

Pediatric Crohn's disease,iron deficiency anemia and intravenous iron treatment: a follow-up study

Background and aims: Increasing evidence in adults demonstrates efficacy and safety of IV iron in inflammatory Bowel disease (IBD) associated iron deficiency anemia; however, evidence in pediatric patients is yet scarce and no previous study has included a long follow-up. This study aimed to evaluate safety and efficacy of IV iron (primary end point), and the need of re-treatment (secondary end point), in this setting.

Methods: Prospective recruitment (40 months); PCDAI determined before and after treatment; anemia defined according to WHO criteria; IV iron treatment included iron sucrose and ferric carboxymaltose. Primary and secondary endpoints included hemoglobin, serum ferritin, transferrin saturation at baseline and 4-6 weeks after treatment; and the need of re-treatment during the median follow-up period (18 months), respectively.

Results: Nineteen patients (median age: 15.5 years) with remissive/mild disease were included. At recruitment, the median hemoglobin was 10.5?g/dl, (median s-ferritin: 20.1 ug/l, median transferrin saturation; 6%) and 4-6 weeks after treatment was 12.7?g/dl. Median hemoglobin according to age groups before vs. after treatment:?<12 years:11 vs. 12.0?g/dl; females ≥12 years:9.9 vs. 12.6?g/dl; and males ≥12 years:11.1 vs. 13.3?g/dl. Patients with remissive vs. mild disease had median Hb of 10.5?g/dl vs. 10.6?g/dl, and median s-ferritin: 6.8 ug/dl vs. 43.3 ug/dl, respectively). Nine patients were treated with iron sucrose (median dose 672.6?mg/dl) and 10 patients with ferric carboxymaltose (median dose 811.5?mg/dl). No major adverse reactions occurred. Six patients needed re-treatment after a median 15.5 months period.

Conclusions: Our prospective study, concerning pediatric IBD anemia patients with remission/mild disease and a significant follow-up, emphasizes efficacy and safety of IV-iron and the importance of long-term follow-up of iron status.

Summary: In pediatric IBD iron anemia, the evidence supporting the efficacy and safety of IV-iron is scare. This prospective study aims to evaluate the safety and efficacy (short and long term) of IV-iron in these patients. Nineteen pediatric CD patients were evaluated before and after IV iron treatment (40-month period).The median Hb before and after IV iron was 10.5 and 12.7?g/dl, respectively. No major adverse reactions were documented. Six patients needed re-treatment (median period of 15.5 months). This study further demonstrates the efficacy and safety of IV iron. It reinforces the importance of long-term follow-up of the iron status in pediatric CD patients.     

Iron deficiency anemia in older adults: A review

Anemia in older adults is a risk factor for numerous negative outcomes. There is no standard definition, but in most studies, anemia is defined as a hemoglobin value <12 g/dL for women and <13 g/dL for men. Absolute iron deficiency anemia is defined as the combination of anemia and the absence of total body iron. Serum ferritin is the most frequently used diagnostic parameter, but its concentration increases with age and in the presence of inflammatory diseases. Other laboratory tests, such as transferrin saturation, soluble transferrin receptor and the soluble transferrin receptor/ferritin index might provide useful information, but there is a wide variety in the cut‐off values and interpretation of the results. Recent research regarding hepcidin as a central regulator of iron homeostasis is promising, but it has not been used yet for the routine diagnosis of iron deficiency anemia. In older iron deficiency anemia patients, an esophagogastroduodenoscopy and colonoscopy should be initiated in order to identify the underlying bleeding cause. CT colonography can replace a colonoscopy, and in specific cases, a video capsule is recommended. It remains crucial to keep in mind which potential benefits might be expected from these investigations in this vulnerable population, taking into account the comorbidity and life expectancy, and one should discuss in advance the possible therapeutic options and complications with the patient, a family member or a proxy. Oral iron administration is the standard treatment, but parenteral iron is a convenient and safe way to provide the total iron dose in one or a few sessions. Geriatr Gerontol Int 2018; 18: 373–379 .     

The role of iron repletion in adult iron deficiency anemia and other diseases

Iron deficiency anemia (IDA) is the most prevalent and treatable form of anemia worldwide. The clinical management of patients with IDA requires a comprehensive understanding of the many etiologies that can lead to iron deficiency including pregnancy, blood loss, renal disease, heavy menstrual bleeding, inflammatory bowel disease, bariatric surgery, or extremely rare genetic disorders. The treatment landscape for many causes of IDA is currently shifting toward more abundant use of intravenous (IV) iron due to its effectiveness and improved formulations that decrease the likelihood of adverse effects. IV iron has found applications beyond treatment of IDA, and there is accruing data about its efficacy in patients with heart failure, restless leg syndrome, fatigue, and prevention of acute mountain sickness. This review provides a framework to diagnose, manage, and treat patients presenting with IDA and discusses other conditions that benefit from iron supplementation.     

Inflammatory bowel disease and anemia: intravenous iron treatment

Objectives: The main objective of our study was to determinate the effectiveness of intravenous iron treatment with ferric carboxymaltose in inflammatory bowel disease (IBD) patients. Our other objectives were to study parameters that would predict a good response to the treatment and to chart out possible side-effects of the treatment.

Materials and methods: In our retrospective chart review study we collected clinical data and laboratory results related to IBD from medical records of 87 IBD patients who were treated with ferric carboxymaltose in Helsinki University Hospital between 2014 and 2016.

Results: The mean increase in hemoglobin levels of the patients was 24.6?g/l (+?24%) after one month, 27.6?g/l (+?27%) after three months and 26.0?g/l (+?27%) after six months. Nine out of 87 treated patients (10.3%) reported side-effects during the iron infusion. A linear regression model assessing the change in hemoglobin levels after six months demonstrated close correlation with transferrin receptor count (p?=?.004) and ferritin (p?=?.016) with an adjusted R square of 0.463.

Conclusion: Ferric carboxymaltose was found to be an effective and well tolerated treatment for iron deficiency anemia in patients with IBD. The results of our study further strengthen the current knowledge of the effectiveness and safety of the treatment.     

老年缺铁性贫血与幽门螺杆菌感染的临床分析

目的探讨铁剂合并抗幽门螺杆菌(Hp)治疗对老年人缺铁性贫血(IDA)伴Hp阳性慢性胃炎患者的贫血纠正效果,探讨Hp感染与IDA形成的相关性。方法将59例IDA伴Hp阳性慢性胃炎患者,分为A、B2组。A组单纯补铁治疗,B组联合应用补铁及Hp根除治疗;检测治疗前后其血红蛋白及血清铁、总铁结合力、铁蛋白水平,并对Hp进行检测。结果补铁联合抗Hp治疗较单纯补铁治疗效果显著(P<0.05)。结论Hp感染可造成或加重机体铁吸收不良,抗Hp治疗有助于提高IDA伴Hp感染患者的临床疗效。     

Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

Objectives: Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron.

Materials and methods: A retrospective cohort study was designed involving children with inflammatory bowel disease followed in that unit between January 2001 and April 2016. Laboratory results were collected at the moment of diagnosis, after one-year follow-up and prior each IV iron administration performed during the study period. Anemia was defined according to World Health Organization criteria and the iron deficiency was defined using recent guidelines.

Results: Were studied 69 patients 71% had CD and 29% UC. 50.7% were female. Mean patient age at diagnosis was 13.3 years (range 1--17 years). Prevalence of ID and IDA at diagnosis was 76.8% and 43.5%, respectively. After one year follow-up, those values decreased to 68.1% (p?=?.182) and 21.7% (p?=?.002), respectively. Hemoglobin significantly increased (p?<?.001). Intravenous iron was administered to 92.8% of patients. No adverse reactions were reported.

Conclusions: Intravenous iron is the first line in the treatment of Iron deficiency anemia in Inflammatory Bowel disease and it is safe and effective. Persistent anemia and iron deficiency are common.     

Anemia and iron deficiency in heart failure: a review of echocardiographic features

Anemia and iron deficiency are often associated with heart failure, influencing the symptoms and prognosis. Correction of anemia and iron deficiency improves functional capacity and decreases hospitalizations. Many studies have analyzed echocardiographic parameters in iron deficiency and anemia and their evolution after iron treatment; however, the heterogeneity of the results makes it difficult to draw conclusions. The aim of this paper is to review the echocardiographic parameters during anemia and iron deficiency, and their evolution after treatment. Available data suggest that they lead to ventricular and atrial remodeling, a decrease in ventricular contractility, and an alteration of ventricular relaxation, although in heart failure with preserved ejection fraction these changes are not significant. Anemia and iron deficiency also increase systolic pulmonary artery pressure. There is consistent evidence that correction of these comorbidities leads to a reduction in preload and left ventricular cavity dimensions, an improvement in diastolic and load‐independent ventricular systolic function parameters, and a decrease in systolic pulmonary artery pressure. However, the evidence is less consistent about the changes produced in ventricular hypertrophy, load‐dependent systolic function parameters, and E‐wave. Generally, anemia and iron deficiency affect the echocardiographic findings, and correcting these conditions often results in improvement in the affected echocardiographic parameters.     

Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials

Abstract

Background. Helicobacter pylori (H. pylori) infection and iron deficiency anemia are prevalent in disadvantaged populations worldwide. The benefit of H. pylori eradiation for iron deficiency anemia has been extensively studied, but data are still equivocal. Methods. A search in The Cochrane Library, PUBMED, EMBASE, EBM Review databases, Science Citation Index Expanded, and CMB (Chinese Biomedical Literature Database) was performed. Randomized controlled trials (RCTs) comparing anti-H. pylori plus oral iron to oral iron alone for the iron deficiency patients in whom H. pylori was positive were selected for meta-analysis. Reviev Manager 5.0 software was used for the performance of meta-analysis. Results. Sixteen randomized controlled trials totaling 956 patients were included. The meta-analysis showed that the difference from baseline to endpoint of hemoglobin (Hb), serum iron (SI), and serum ferritin (SF) was statistically significantly different between anti-H. pylori treatment plus oral iron and oral iron alone (SMD, Hb 1.48; 95% CI, 0.96, 2.00; p < 0.00001; SI 1.15; 95% CI, 0.87, 1.43; p < 0.00001; SF 1.84; 95% CI, 1.20, 2.48; p < 0.00001, respectively). Conclusions. Our study suggests that treatment of H. pylori infection could be effective in improving anemia and iron statue in IDA patients infected by H. pylori, particularly in patients with moderate or severe anemia.     

Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: A pilot study

Background

Pulmonary arterial hypertension (PAH) is a progressive condition harboring a poor prognosis. Iron deficiency in PAH correlates with disease severity and mortality. While replacement therapy may be beneficial, dietary iron absorption is impaired in PAH patients by hepcidin, a key regulatory protein of iron homoeostasis. We therefore assessed the therapeutic potential and safety of intravenous iron supplementation in patients with PAH and iron deficiency.

Methods

20 patients with PAH and iron deficiency, who were on stable targeted PAH therapy, received a single infusion of ≤ 1000 mg ferric carboxymaltose. All patients were assessed at baseline and two months after iron treatment. Exercise capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The effects were compared to 20 matched patients with stable PAH without iron deficiency who did not receive ferric carboxymaltose.

Results

In iron deficient patients, iron supplementation led to a marked improvement of iron status (serum iron 5.7 ± 0.4 to 11.1 ± 1.1 μmol/L, ferritin 29.3 ± 6.3 to 145.2 ± 25.4 μg/L, transferrin saturation 7.5 ± 0.7 to 19.3 ± 2.3%, all p ≤ 0.001). Iron-deficient patients receiving ferric carboxymaltose showed a significant increase of the 6MWD from 346.5 ± 28.3 to 374.0 ± 25.5 m (p = 0.007), whereas no significant changes were found in the control group not receiving iron supplementation (6MWD 389.9 ± 25.3 to 379.6 ± 26.2 m; n.s.), resulting in a net increase in the 6MWD of 37.8 m (p = 0.003). This was associated with an improvement in QoL (SF-36 score from 44.3 ± 3.7 to 50.6 ± 3.6; p = 0.01). Only minimal side-effects were reported.

Conclusions

These data indicate that parenteral iron supplementation with ferric carboxymaltose significantly improves exercise capacity and QoL and is well tolerated in patients with PAH and iron deficiency, and when administered in addition to targeted PAH therapies. Our results provide proof of concept for further studies evaluating the potential of iron as an adjunct in PAH treatment on a larger scale.     

Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease

Objective. Iron therapy may reinforce intestinal inflammation by catalysing production of reactive oxygen species. The effects of oral ferrous fumarate and intravenous iron sucrose on clinical disease activity and plasma redox status were investigated in patients with inflammatory bowel disease (IBD).Material and methods. Nineteen patients with iron deficiency anaemia and Crohn's disease (11) or ulcerative colitis (8) were included in a crossover study. The patients were randomly assigned to start treatment with ferrous fumarate (Neo-fer®) 120 mg orally once daily or iron sucrose (Venofer®) 200 mg intravenously 3 times during a period of 14 days. Clinical disease activity assessment and blood and faecal analysis were performed on days 1 and 15.Results. Following oral ferrous fumarate clinical disease activity (p=0.037), general well-being score (i.e. patients felt worse) (p=0.027) and abdominal pain score (p=0.027) increased, while no changes were seen following iron sucrose treatment. C-reactive protein (CRP) and faecal calprotectin were unchanged after both treatments. As compared with iron sucrose, ferrous fumarate increased Crohn's disease activity index (CDAI) scores of general well-being (p=0.049), whereas alterations in clinical disease activity (p=0.14) and abdominal pain score (p=0.20) did not differ. Ferrous fumarate did not significantly alter plasma malondialdehyde (MDA) or plasma antioxidants. Iron sucrose increased plasma MDA (p=0.004) and decreased plasma vitamin C (p=0.017) and betacarotene (p=0.008).Conclusions. Oral ferrous fumarate, but not intravenous iron sucrose, increased clinical disease activity in IBD patients. Intravenous iron sucrose increased intravascular oxidative stress.     

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     

缺铁性贫血患者抗幽门螺旋杆菌治疗的价值

目的：了解幽门螺旋杆菌（HP）感染对缺铁性贫血（IDA）发病的影响及抗HP治疗对改善贫血的价值。方法：对116例IDA患者补铁治疗并检测HP感染的情况。分组：A组为给予去除缺铁原因治疗和补铁治疗可以达到IDA痊愈者,B组为无明显缺铁原因但单纯补铁效果不好的IDA患者。对B组患者给予抗HP治疗,观察抗HP治疗前后患者Hb、平均红细胞体积（MCV）、平均红细胞血红蛋白含量（MCH）、血清铁蛋白（SF）的变化。结果：116例IDA患者中,A组74例给予去除缺铁原因治疗和（或）补铁治疗可以达到IDA痊愈,其中HP感染43例,感染率58.1%;B组42例无明显缺铁原因但是单纯补铁效果不好的IDA患者中HP感染者36例,感染率85.7%,2组间HP感染率的差异有统计学意义。对B组中HP阳性者给予抗HP治疗,抗HP治疗有效者Hb、MCV、MCH、SF较治疗前有明显提高。结论：HP感染可能与IDA的发生有关,清除HP的治疗可改善IDA的疗效。