Iron deficiency anemia in inflammatory bowel disease

Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.     

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.     

Treatment of anaemia in inflammatory bowel disease with iron sucrose

Background: Inflammatory bowel disease (IBD)‐associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. Methods: Sixty‐one patients with IBD and anaemia (average haemoglobin 97?g/L) were treated with iron sucrose (iron dose 1.4?±?0.5?g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of ≥20?g/L or to normal haemoglobin levels (≥120?g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. Results: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty‐four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow‐up period of 117?±?85 (4–291) (mean?±?s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. Conclusions: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow‐up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.     

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.     

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.     

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.     

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.     

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 ...     

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.     

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.     

铁代谢指标测定对慢性病贫血并发缺铁的诊断意义

目的 :了解血清铁蛋白 (SF)、转铁蛋白饱和度 (TS)、血清转铁蛋白受体 (sTFR)及sTFR/log(SF)等外周血铁代谢指标对缺铁性贫血 (IDA)、慢性病贫血 (ACD)和慢性病贫血并发缺铁 (ACD/ID)的鉴别诊断意义。方法 :病例为IDA患者 18例 ,ACD患者 2 0例 ,其中 10例为ACD/ID患者。SF测定采用微粒酶免疫法 ,TS测定采用化学发光法 ,sTFR测定采用双夹心抗体酶联免疫吸附法。结果 :IDA患者的SF值、TS值显著低于ACD患者 ,其sTFR、sTFR/log(SF)值显著高于ACD患者。ACD患者中 ,ACD/ID患者与无缺铁的ACD(ACD/IR)患者间SF值无显著差别 ;但ACD/ID患者的TS值明显低于ACD/IR患者 ,而sTFR和sTFR/log(SF)值则显著高于ACD/IR患者。TS<4 0 %对ACD/ID检出的敏感性为 10 0 % ,特异性为 6 7% ;sTFR >30nmol/L对ACD/ID检出的敏感性为 90 % ,特异性为 82 % ;sTFR/log(SF) >2 0对ACD/ID检出的敏感性和特异性均为 90 %。结论 :新的铁代谢指标sTFR ,尤其是sTFR/log(SF)是传统铁代谢指标的必要补充 ,联合应用上述铁代谢指标可对ACD、IDA和ACD/ID患者进行准确的鉴别诊断。     

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.     

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     

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.     

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.