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.     

Intravenous iron in inflammatory bowel disease

The prevalence of anemia across studies on patients with inflammatory bowel disease （IBD） is high （30%）. Both iron deficiency （ID） and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher （45%）. Anemia and ID negatively impact the patient＇s quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin （Hb） and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous （IV） compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for IV iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles： iron gluconate and iron sucrose （lower single doses）, and iron dextran and ferric carboxymaltose （higher single doses）. After the initial resolution of anemia and the repletion of iron stores, the patient＇s hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New IV preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management,provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.     

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 ...     

Frequency,types, and treatment of anemia in Turkish patients with inflammatory bowel disease

AIM to specify the type and prevalence of anemia along with a treatment approach for inflammatory bowel disease(IBD).METHODS We conducted a retrospective study on 465 patients who were diagnosed with IBD and followed up at our hospital from June 2015 to June 2016 [male: 254, female: 211; average age: 47 ± 14.4; Crohn's disease(CD): 257, Ulcerative Colitis(UC): 208]. Epidemiological and clinical data, such as sex, age, age of diagnosis, type of IBD, disease extension, disease behavior and duration, treatments for IBD and anemia, and surgical history were obtained for each patient. Per World Health Organization guidelines, anemia was diagnosed for males if hemoglobin values were less than 13 g/dL and for females if hemoglobin values were less than 12 g/d L.RESULTS We determined that 51.6% of the patients had anemia, which was more frequent in women then men(64% vs 41.3%, P 0.001). Anemia frequency was higher in CD cases(57.6%) than in UC cases(44.2%)(P = 0.004). CD involvements were as follows: 48.2% in ileal involvement, 19% in colonic involvement, and 32.8% in ileocolonic involvement. Furthermore, 27.5% of UC patients had proctitis(E1) involvement, 41% ofthem had involvement in left colitis(E2), and 31.5% had pancolitis involvement. There was no significant relationship between anemia frequency and duration of disease(P = 0.55). Iron deficiency anemia(IDA) was the most common type of anemia in this cohort. Moreover, because anemia parameters have not been evaluated during follow-up of 15.3% of patients, the etiology of anemia has not been clarified. Fifty percent of patients with anemia received treatment. Twentythree percent of IDA patients had oral iron intake and forty-one percent of IDA patients had parenteral iron treatment. Fifty-three percent of patients who were suffering from megaloblastic anemia received B12/folic acid treatment.CONCLUSION We found out that almost half of all IBD patients(51.6%) had anemia, the most frequent of which was IDA. Almost half of these patients received treatment. We should increase the treatment rate in our IBD patients that have anemia.     

Iron deficiency anemia in celiac disease

Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.     

Diagnosing anemia in inflammatory bowel disease: Beyond the established markers

The main types of anemia in inflammatory bowel disease (IBD) are iron deficiency anemia (IDA) and anemia of inflammatory etiology, or anemia of chronic disease (ACD). In the management of IBD patients with anemia it is essential for the physician to diagnose the type of anemia in order to decide in an evidence-based manner for the appropriate treatment. However, the assessment of iron status in IBD in many cases is rather difficult due to coexistent inflammation. For this assessment several indices and markers have been suggested. Ferritin, seems to play a central role in the definition and diagnosis of anemia in IBD and transferrin, transferrin saturation (Tsat), and soluble transferrin receptors are also valuable markers. All these biochemical markers have several limitations because they are not consistently reliable indices, since they are influenced by factors other than changes in iron balance. In this review, in addition to them, we discuss the newer alternative markers for iron status that may be useful when serum ferritin and Tsat are not sufficient. The iron metabolism regulators, hepcidin and prohepcidin, are still under investigation in IBD. Erythrocytes parameters like the red cell distribution width (RDW) and the percentage of hypochromic red cells as well as reticulocyte parameters such as hemoglobin concentration of reticulocytes, red blood cell size factor and reticulocyte distribution width could be useful markers for the evaluation of anemia in IBD.     

Emerging causes of iron deficiency anemia refractory to oral iron supplementation

While oral iron supplementation is commonly used throughout many clinical setting,treatment with intravenous(IV) iron has historically been reserved for specific settings,such as chronic kidney disease,gynecologic issues,and anemia associated with cancer and its treatments.However,the use of IV iron has begun to gain popularity in the treatment of iron deficiency anemia(IDA) associated with two conditions that are being seen more frequently than in years past:patients who are status post gastric bypass procedure and those with inflammatory bowel disease(IBD).The Roux-en-Y procedure involves connecting a gastric pouch to the jejunum,creating a blind loop consisting of distal stomach,duodenum,and proximal jejunum that connects to the Roux limb to form a common tract.IDA occurs in 6%-50% of patients who have undergone a gastric bypass,the etiology being multifactorial.The proximal gastric pouch,the primary site of gastric acid secretion,is bypassed,resulting in a decreased ability to metabolize molecular iron.Once metabolized,most iron is absorbed in the duodenum,which is entirely bypassed.After undergoing bypass procedures,most patients significantly limit their intake of red meat,another factor contributing to post-bypass IDA.Chronic anemia occurs in approximately 1/3 of patients who suffer from IBD,and almost half of all IBD patients are iron deficient.IBD leads to IDA through multiple mechanisms,including chronic intestinal blood loss,decreased absorption capabilities of the duodenum secondary to inflammation,and an inability of many IBD patients to tolerate the side effects of oral ferrous sulfate.In this study,we reviewed the charts of all patients who received IV iron at Sylvester Comprehensive Cancer Center/University of Miami Hospital Clinic from January 2007 to May 2012.The most common indications for IV iron were for issues related to cancer and its treatment(21.9%),IBD(20.1%),and gastric bypass(15.0%).Of the 262 patients who received IV iron,230 received iron sucrose and 36 received iron dextran.While doses of 100,200,300,and 400 mg of iron sucrose were given,100 and 200 mg were by far the most common dosages used,122 and 120 times,respectively.The number of dosages of iron sucrose given ranged from 1 to 46,with a mean of 5.5 and a median of 4 doses.The average dose of iron dextran given was 870.5 mg,with 1000 mg being the most common dosage used.Most patients(22 of 36) who received iron dextran only received one dose.While patients with traditional indications for IV iron,such as gynecologic issues and kidney disease,still were represented in this study,we expect to see a continued increase in physicians using IV iron for emerging gastrointestinal indications,especially considering the increased safety of new low-molecular formulations.     

Treatment with Noripurum EV® is effective and safe in pediatric patients with inflammatory bowel disease and iron deficiency anemia

Objectives: To evaluate the therapeutic response and adverse effects of Noripurum EV^® in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency anemia.

Materials and methods: Cohort study involving patients with Crohn’s disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV^®. Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30µg/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100µg/l and transferrin saturation <16%. The total dose of Noripurum EV^® was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic success.

Results: Noripurum EV^® was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p?<?.001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0–6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p?=?.031) than those who did not (31.2%). No adverse events were reported.

Conclusion: Noripurum EV^® in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.     

Vitamin D deficiency in inflammatory bowel disease: prevalence and predictors in a Norwegian outpatient population

Background and aim: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD.

Methods: Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory.

Results: In total, 49% (200/408) of the patients had a 25-OH-D concentration <50?nmol/L, including 53% (122/230) of the Crohn’s disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >100?mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency.

Conclusions: Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.     

口服耐受与炎症性肠病

口服耐受是机体对口服抗原产生的特异性无应答或低应答状态.低剂量口服抗原主要通过调节性T细胞分泌抑制性细胞因子介导免疫抑制,高剂量口服抗原主要引起T细胞清除或T细胞失能.多次低剂量口服结肠炎提取蛋白或正常结肠提取蛋白均能缓解实验性结肠炎.目前,多次低剂量口服自体结肠提取蛋白已初步应用于临床试验,并证明是安全的治疗方案.充分发挥口服耐受对炎症性肠病的临床疗效仍需深入研究.     

Current evaluation and management of anemia in patients with inflammatory bowel disease

Introduction: Anemia is a common extraintestinal manifestation in IBD patients and considerably impacts disease prognosis, hospitalization rates and time lost from work. While iron deficiency anemia is predominant, combinations of hematimetric and biochemical markers enable detection and targeted therapy of other etiologies including vitamin B12/folic acid deficiencies, hemolysis, myelosuppression and pharmacotherapies.

Areas covered: Current literature was searched for articles focusing on etiology, diagnostics and therapy of anemia in IBD. In the light of their own experience, the authors describe the physiology of anemia in IBD and present current evidence endorsing diagnostic and therapeutic options, focusing particularly on non-iron-related etiologies.

Expert commentary: Anemia in IBD is polyetiological, reaching far beyond iron deficiency anemia. While clinicians need to be aware of the increasing pallet of diagnostic tools and therapeutic options, detailed studies are needed to develop more convenient test procedures, long-term treatment and monitoring strategies, and unified guidelines for daily practice.     

Anemia in inflammatory bowel disease: A neglected issue with relevant effects

Anemia,a common complication associated with inflammatory bowel disease(IBD),is frequently overlooked in the management of IBD patients.Unfortunately,it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population.Anemia in IBD is pathogenically complex,with several factors contributing to its development.While iron deficiency is the most common cause,vitamin B12and folic acid deficiencies,along with the effects of pro-inflammatory cytokines,hemolysis,drug therapies,and myelosuppression,have also been identified as the underlying etiology in a number of patients.Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD.Because the diagnosis of anemia in IBD often presents a challenge,combinations of several hematimetric and biochemical parameters should be used.Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia,anemia due to chronic disease,or mixed anemia in IBD patients.With regard to treatment,the newly introduced intravenous iron formulations have several advantages over orally-administerediron compounds in treating iron deficiency in IBD.In special situations,erythropoietin supplementation and biological therapies should be considered.In conclusion,the management of anemia is a complex aspect of treating IBD patients,one that significantly influences the prognosis of the disease.As a consequence,its correction should be considered a specific,first-line therapeutic goal in the management of these patients.     

Anemia and digestive diseases： An update for the clinician

Too often anemia is considered a rare or unimportant manifestation in inflammatory bowel disease （IBD）. However, over the last 10 years a number of studies have been conducted and the most relevant conclusions obtained are： （1） anemia is quite common in IBD; （2） although in many cases anemia parallels the clinical activity of the disease, many patients in remission have anemia, and iron, vitamin B12 and/or folic acid deficiency; （3） anemia, and also iron deficiency without anemia, have important consequences in the clinical status and quality of life of the patient; （4） oral iron can lead to gastrointestinal intolerance and failure of treatment; （5） intravenous iron is an effective and safe way to treat iron deficiency; （6） erythropoietin is needed in a significant number of cases to achieve normal hemoglobin levels. Thus, the clinician caring for IBD patients should have a comprehensive knowledge of anemia, and apply recently published guidelines in clinical practice.     

炎症性肠病合并贫血的研究进展

贫血是炎症性肠病(IBD)患者常见的并发症之一,会导致生活质量下降,也可增加患者的住院频率。据报道IBD并发贫血的发病率为6～74[1]。IBD患者贫血的发病机制尚未完全明了,铁摄入与丢失的负平衡、慢性病所致贫血、VitB12和叶酸缺乏、药物介导、炎症因子、溶血等众多因素均可能参与贫血的发生。过去普遍认为贫血是IBD不可避免的伴随症状,往往重视度不够,但最近的观点强调,贫血是此类患者明确的治疗内容。     

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 .     

Reticulocyte hemoglobin content (MCHr) in the assessment of iron deficient erythropoiesis in inflammatory bowel disease

BackgroundIn conditions associated with inflammation, biochemical parameters alone could be inadequate for assessing iron status. We investigated the potential utility of mean reticulocyte hemoglobin content (MCHr) in the assessment of the erythropoiesis status in inflammatory bowel disease (IBD).MethodsWe recruited 124 anemic outpatients with IBD. Serum iron, transferrin and ferritin were tested. Complete blood counts were performed on a CELL-DYN Sapphire analyzer (Abbott Diagnostics).Differences among groups were assessed using analysis of variance, considering P < 0.05 to be significant.Receiver operating characteristic analysis was used to assess the diagnostic performance of MCHr for detecting iron deficient erythropoiesis.The reference used as an indicator of insufficient iron availability was transferrin saturation <20%.ResultsOverall, 47.6% of the patients had iron deficiency anemia (IDA) and 31.5% anemia of chronic disease (ACD), while the others (20.9%) had mixed anemia.Patients with ACD or mixed anemia showed functional iron deficiency: normal or high ferritin and low MCHr. The area under curve was 0.858 (95% CI 0.742–0.942), considering a cut off 30.3 pg, the sensitivity was 82.2%, specificity 83.3%.ConclusionsMCHr provides information on iron availability in IBD patients. It is a reliable test to assess iron supply for erythropoiesis.     

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas

Background

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes.

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn’s disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.AIMTo determine proportions and factors associated with vitamin C deficiency in CD and UC patients.METHODSIn this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.RESULTSOf 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without.CONCLUSIONVitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.