A Prospective Randomised Controlled Trial of a Single Intravenous Infusion of Ferric Carboxymaltose vs Single Intravenous Iron Polymaltose or Daily Oral Ferrous Sulphate in the Treatment of Iron Deficiency Anaemia in Pregnancy

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000 mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000 mg of IPM (n = 82) over 2 hours against 325 mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9 µg/L, with a mean of 13 µg/L. The mean haemoglobin (Hb) was 114 g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35 g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08 g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26 g/L; 95% CI: −2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166 µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145 µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5 µg/L; 95% CI: −23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms.In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.     

Iron treatment and inflammatory bowel disease: What happens in real practice?

Background and aimsIron deficiency anaemia (IDA), the most common extra-intestinal complication of inflammatory bowel disease (IBD), negatively impacts quality of life. We audited the recent practice of anaemia treatment in an unselected IBD population.MethodsA questionnaire was distributed to adult IBD outpatients in a university hospital to assess the form and frequency of iron prescribed, duration of use, side effects, and completion of therapy. The efficacy of treatment was determined by the resolution of anaemia and change in haemoglobin from baseline.ResultsOf 87 IBD patients (60 patients with Crohn's disease, 25 with ulcerative colitis, 2 with microscopic colitis), 85 received various dosing regimens of iron tablets; 15 patients also received IV iron. Side effects were reported in 43 (51%) patients, with no clear relationship to dose prescribed and 26 (32%) patients were unable to complete the intended course. Only 36 (42%) patients completed the course of oral iron without side effects and in these patients, haemoglobin normalised in about 30%. Their median haemoglobin change was 12.5 (5.3–23.5) g/l. The median duration of treatment in those without side effects was 4.5 months, and in those with adverse effects was 2 months. Only one adverse effect was reported for IV iron.ConclusionsTreatment with oral iron results in failure to control anaemia in 2 out of 3 IBD patients, which is likely in part to be due to the side effects reported by over half of patients. Patients failing to tolerate or adequately respond to therapy should be offered alternative treatment.     

Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease

Background and aimsAnemia is a frequent complication of inflammatory bowel disease (IBD). Hepcidin, a key mediator in this anemia, is up-regulated by high iron levels and inflammation, and serum levels are elevated in IBD. However, the extent of inflammatory activity and iron deficiency for the regulation of hepcidin is not known. This study aimed to evaluate serum hepcidin levels in anemic and non-anemic IBD patients, with iron or non-iron deficiency, and active or inactive disease.MethodsThis retrospective, observational study analyzed serum hepcidin levels from 247 patients with IBD (130 Crohn's patients and 117 with ulcerative colitis) recruited at Swiss Inflammatory Bowel Disease Cohort Study centers. Patients were divided into 5 different groups using criteria of active and inactive diseases (C-reactive protein, and CDAI/MTWAI = disease activity-index), anemia (hemoglobin) and iron deficiency (ferritin) and compared to healthy controls with no signs of anemia and normal ferritin levels. Hepcidin was measured using enzyme-linked immunosorbent assay.ResultsIndependent of inflammatory activity, all patients with decreased ferritin (< 30 μg/L) had significantly lower hepcidin levels when compared to patients and healthy controls having normal ferritin (> 30 μg/L). A significant correlation between serum ferritin levels and serum hepcidin was found (Spearman's Rho = 0.491; p < 0.001). A backward multi-linear stepwise regression analysis showed that only ferritin, and none of the inflammatory markers or age and sex correlated significantly (p = 0.005) with hepcidin.ConclusionThis retrospective analysis suggests that iron deficiency is the key trigger for hepcidin regulation in IBD patients with anemia.     

Anemia-prevalence and risk factors in pregnancy

BackgroundTo assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status.MethodsA longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis.ResultsThe prevalence of decreased iron stores (ferritin < 20 μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb < 110 g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p = 0.004 and p = 0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p = 0.027) and in patients older than 30 years, a significant increase of decreased iron stores (p = 0.018).ConclusionsIn our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia.     

Diagnosis and management of iron deficiency anemia in patients with IBD

Anemia is the most prevalent extraintestinal complication of IBD. It can affect quality of life and ability to work, and can also increase the hospitalization rate in patients with IBD. Although the causes of anemia in IBD are multifactorial, iron deficiency anemia (IDA) is the most common. Assessment of the iron status of patients who have a condition associated with inflammation, such as IBD, by using common biochemical values is insufficient. However, new indices of iron metabolism (for instance ferritin:transferrin receptor ratio, reticulocyte hemoglobin content or percentage of hypochromic red blood cells) may help to improve the assessment of iron status in patients with IBD. The treatment of IDA traditionally involves oral iron supplementation. However, because of extensive gastrointestinal adverse effects, and data showing that the use of oral iron in IBD may be associated with disease exacerbation, current guidelines suggest that iron supplementation in IBD should be administered intravenously. This Review provides an overview of iron homeostasis in health before discussing diagnostic and therapeutic strategies for IDA in patients with IBD.     

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia.MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin < 100 μg/L and functional ID was defined as normal serum ferritin (100–300 μg/L) with low TSAT (<20%).ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89 ± 0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p = 0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb.ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.     

Therapy experiences and preferences among patients with anemia: Results of a cross-sectional survey among Italian patients with inflammatory bowel disease

BackgroundAnemia represents one of the most common and often the least treated complications of inflammatory bowel disease (IBD).AimsOur study investigates experiences and preferences concerning anemia treatment in patients with IBD.MethodsIBD patients previously diagnosed with anemia were invited to participate in an anonymous survey between July and September 2015, which assessed demographic and clinical data, and experiences regarding anemia treatment.ResultsA total of 118 IBD patients were invited to participate in the study, of which 100 (85%) were included in the analysis. Seventy-five percent of patients reported a high personal burden related to intravenous therapy, while the majority of companions (76%) declared a moderate burden. The increased importance assigned to the possibility of a single session treatment was significantly associated with age (Beta = 0.01; p = 0.03), working status (Beta = 0.02; p = 0.04), anemia severity (severe vs. mild, Beta = 0.42; p = 0.03), and intravenous treatment (Beta = 0.44; p = 0.001).ConclusionsMost patients reported a high personal and a moderate companions’ burden. Having the possibility of effective single dose intravenous therapy was of great importance. Patients’ perspective provides key information for evaluating the indirect costs of anemia treatment in IBD which, according to the health technology assessment approach, could be useful in a patient centered decision making process.     

Hepcidin is a key mediator of anemia of inflammation in Crohn's disease

Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD.MethodsWe enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin < 12 g/dL and < 13.5 g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded.ResultsThere was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r = 0.853, p < 0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r = 0.723, p = 0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r = 0.546, p = 0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r = 0.528, p = 0.029).ConclusionWe demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.     

A comprehensive evaluation of the gastrointestinal tract in iron-deficiency anemia with predefined hemoglobin below 9 mg/dL: A prospective cohort study

BackgroundAnemia is defined as hemoglobin below the cutoff of normal in studies examining the gastrointestinal (GI) tract in iron-deficiency anemia (IDA). Although the risk of GI cancer (GIC) increases as hemoglobin decreases, guidelines do not usually recommend hemoglobin thresholds for IDA investigation.MethodsTo elucidate whether underlying GI disorders explain the different hemoglobin values and clinical outcomes observed initially in IDA patients referred for GI workup, we prospectively investigated the diagnostic yield of a thorough GI examination in consecutive IDA adults with predefined hemoglobin <9 g/dL and no extraintestinal bleeding.Results4552 patients were enrolled over 10 years. 96% of 4038 GI lesions were consistent with occult bleeding disorders and 4% with non-bleeding disorders. Predominant bleeding disorders included upper GI ulcerative/erosive lesions (51%), GIC (15%), and angiodysplasias (12%). Diffuse angiodysplasias (45% of angiodysplasias) and GIC showed the lowest hemoglobin values (6.3 [1.5] and 6.4 [1.3] g/dL, respectively). While the spread (diffuse vs. localized) and number (<3 vs. ≥3) of angiodysplasias correlated with the degree of anemia, hemoglobin values were lower in GIC with vs. without ulcerated/friable lesions (6.0 [1.1] vs. 7.0 [1.2] g/dL, P < 0.001).ConclusionNot only GIC but also diffuse angiodysplasias caused the most severe anemia in IDA with predefined hemoglobin values <9 g/dL.     

The impact of hospitalization on the performance of capsule endoscopy (CE)

BackgroundFor proper evaluation of capsule endoscopy (CE), a complete examination is necessary.AimWe evaluated risk factors of an incomplete CE with focus on patient hospitalization.MethodsWe retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP).ResultsWe report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18–90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6 min (p = 0.0001). The shortest SBTT was found in out-patients without FAP (267.5 min, p < 0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p = 0.036). We found pathologic lesions in the last 30 min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone.ConclusionIn-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.     

Serum Ferritin Levels Predict All-Cause and Infection-Cause 1-Year Mortality in Diabetic Patients on Maintenance Hemodialysis

BackgroundThe aim of this study was to assess the relationship between the serum ferritin level and the 1-year outcome in diabetic maintenance hemodialysis (MHD) patients.MethodsThe prospective clinical study enrolled 187 diabetic MHD patients from a university hospital in Taiwan. All the patients were divided into 3 groups according to their serum ferritin levels: group I (<200 ng/mL; n = 71), group II (200–700 ng/mL; n = 97), and group III (>700 ng/mL; n = 19). A total of 26 demographic, clinical, and laboratory variables were analyzed as predictors of the 1-year mortality.ResultsThere were no significant differences between these 3 groups except in their erythropoietin usage, hemoglobin, transferrin saturation, and high-sensitive C-reactive protein levels. The 1-year mortality rates were 9.2%, 11.4%, and 46.2% in groups I, II, and III, respectively. Group I and group II patients had a lower 1-year mortality rate than group III patients (log-rank test; χ² = 8.807; P = 0.0112).ConclusionThe study suggested that serum ferritin levels predict both all-cause and infection-cause 1-year mortality in diabetic patients on MHD. In such patients, the serum ferritin levels are associated with both iron stores and the inflammation status.     

Viral eradication restores normal iron status in chronic hepatitis C patients with abnormal iron studies

Introduction and objectivesAbnormal serum iron studies are seen in a third or more of patients with chronic hepatitis C infection (HCV), where they have been linked to accelerated fibrosis progression and increased risk of hepatocellular carcinoma and sometimes lead to concern for coexisting hereditary hemochromatosis. The aim of this study was to assess the effect of HCV eradication in patients with abnormal serum iron studies prior to treatment with direct-acting antiviral agents (DAAs).PatientsHCV-infected subjects with iron studies obtained before and after successful treatment with DAAs were identified (n = 27). All had one or more abnormal iron test before treatment.ResultsFollowing HCV eradication, serum iron, transferrin-iron saturation and ferritin levels decreased significantly (pre- versus post-treatment, p < 0.01 for each). Serum iron and/or transferrin-iron saturations normalized in 16/19 subjects and raised ferritin levels returned to the normal range in 14/18 subjects, including several with pretreatment transferrin-iron saturation >90% and/or serum ferritin >1000 ng/mL. Elimination of HCV infection was associated with a significant reduction in post-treatment ferritin levels even among subjects whose ferritin levels were within normal limits at baseline. Risk factors for other conditions associated with abnormal iron status were present in the few cases in which iron studies failed to normalize following DAA treatment.ConclusionsEradication of HCV infection restores normal iron status in most patients with abnormal iron tests, including those whose baseline parameters are suggestive of hemochromatosis.     

Current practice in the diagnosis and management of IBD-associated anaemia and iron deficiency in Germany: The German AnaemIBD Study

Background/aimAnaemia is a common complication in inflammatory bowel disease (IBD), frequently resulting from iron deficiency. IBD guidelines advocate intravenous iron administration although some patients respond to oral supplementation. This non-interventional study investigates the current status of anaemia management in German IBD patients.MethodsBaseline data on pre-study treatment for anaemia were retrospectively analysed in IBD patients with anaemia participating in a prospective trial of the efficacy and safety of ferric carboxymaltose. Data were collected from 55 German gastroenterological centres up to August 2010. Subjects had received care at their centre for at least 12 months prior to baseline.Results193 cases of IBD-associated anaemia (115 Crohn's disease, 77 ulcerative colitis) were analysed (mean age: 39 years (18–83), 79 (41%) males). Anaemia and iron status were usually assessed by haemoglobin (100%), serum ferritin (97%), and transferrin saturation (82%). In the previous 6 months, only 84 patients (43.5%) had been treated for anaemia: 47 (56%) with oral iron, 13 (15%) parenteral iron, 16 (19%) oral plus parenteral iron and 8 (10%) transfusions. No patients received erythropoietin stimulating agents.ConclusionAlthough intravenous iron supplementation is recommended in IBD patients, current German practice still relies on oral therapy, even in severe anaemia. The high incidence of severe anaemia in this cohort reflects inadequate iron replacement and status monitoring. While the proportion of IBD patients with inadequately treated anaemia/iron deficiency is unknown, greater awareness of existing guidelines for iron deficiency management in IBD patients appears necessary.     

Long-term outcome of tumor necrosis factor alpha antagonist's treatment in pediatric Crohn's disease

BackgroundAnti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD.MethodsThe long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed.Results120 patients [101 crohn's disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2–90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p < 0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p < 0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p < 0.001).The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p = 0.04 and 0.02 respectively).ConclusionsOur long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.     

Monitoring inflammatory bowel disease activity: Clinical activity is judged to be more relevant than endoscopic severity or biomarkers

BackgroundThere is increasing evidence for the clinical relevance of mucosal healing (MH) as therapeutic treatment goal in inflammatory bowel disease (IBD). We aimed to investigate by which method gastroenterologists monitor IBD activity in daily practice.MethodsA questionnaire was sent to all board-certified gastroenterologists in Switzerland to specifically address their strategy to monitor IBD between May 2009 and April 2010.ResultsThe response rate was 57% (153/270). Fifty-two percent of gastroenterologists worked in private practice and 48% worked in hospitals. Seventy-eight percent judged clinical activity to be the most relevant criterion for monitoring IBD activity, 15% chose endoscopic severity, and 7% chose biomarkers. Seventy percent of gastroenterologists based their therapeutic decisions on clinical activity, 24% on endoscopic severity, and 6% on biomarkers. The following biomarkers were used for IBD activity monitoring: CRP, 94%; differential blood count, 78%; fecal calprotectin (FC), 74%; iron status, 63%; blood sedimentation rate, 3%; protein electrophoresis, 0.7%; fecal neutrophils, 0.7%; and vitamin B12, 0.7%. Gastroenterologists in hospitals and those with ≤ 10 years of professional experience used FC more frequently compared with colleagues in private practice (P = 0.035) and those with > 10 years of experience (P < 0.001).ConclusionsClinical activity is judged to be more relevant for monitoring IBD activity and guiding therapeutic decisions than endoscopic severity and biomarkers. As such, the accumulating scientific evidence on the clinical impact of mucosal healing does not yet seem to influence the management of IBD in daily gastroenterologic practice.     

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.     

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD)

Purpose of Review

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient’s quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients.

Recent Findings

The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future.

Summary

Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for therapy with iron supplementation whereas IV administration of iron is recommended in patients with clinically active IBD, or for patients who are previously intolerant to oral iron, with hemoglobin levels below 10 g/dL, and in patients who need erythropoiesis-stimulating agents (ESAs). As the recurrence of anemia is common after resolution, the monitoring for recurrent anemia is equally important during the course of therapy.

     

Recombinant human erythropoietin in patients with inflammatory bowel disease and refractory anemia: A 15-year single center experience

Aim of the studyTo describe our 15-year experience on the patients' response and safety to the use of EPO in IBD patients with refractory anemia.Patients–MethodsSingle center retrospective chart analysis of all IBD patients receiving EPO for the period 1994–2009. Patients with resistant anemia not responding to I.V. iron therapy were enrolled. Concommitant medication, medical and laboratory data on short and long-term patients' responses and safety were recorded.ResultsIn total 820 IBD files were reviewed and among 78 patients treated with I.V. iron we identified 26 patients who received EPO in concordance to our inclusion criteria. Azathioprine or methotrexate was administered in 17 patients and 7 patients received concomitant Infliximab. After EPO, 22/26 patients (84.6%) responded and peripheral blood parameters were significantly improved and blood transfusions were significantly decreased (p < 0.001). Erythropoietin dose was increased in three non-responders while two patients required emergency transfusions. No adverse events were recorded.ConclusionsIn anemic IBD patients who are refractory to I.V. iron monotherapy, administration of EPO significantly improved peripheral blood parameters with safety. Prospective controlled trials are needed to confirm positive patients' response to EPO and identify those patients who are more likely to benefit.     

Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese IBD patients

BackgroundAlthough 6-mercaptopurine (6-MP) and azathioprine (AZA) are prescribed at lower doses, their efficacy in patients with inflammatory bowel disease (IBD) in Japan is comparable to that in Europe/America. However, there has been no report concerning the measurement of erythrocyte 6-thioguanine nucleotides (6-TGN), which is an active metabolite of 6-MP or AZA, in Japanese IBD patients. This study was designed to elucidate the pharmacokinetic–pharmacodynamic properties of 6-MP and AZA in Japanese patients by measurement of erythrocyte 6-TGN level.Methods134 adult patients (99 males; 35 females) with IBD (75 ulcerative colitis; 59 Crohn's disease) who had been receiving a constant dose of 6-MP or AZA for three months or longer were enrolled. Erythrocyte 6-TGN levels were measured using the low-pressure gradient HPLC method, and correlated with treatment efficacy. The genetic polymorphism of thiopurine methyltransferase (TPMT) genotype was also assessed.ResultsThe mean erythrocyte 6-TGN level (mean ± SD) was 342.3 ± 220.9 pmol/8 × 10⁸RBC, which was supposed to be therapeutic concentration, although the mean daily doses of 6-MP and AZA were no more than 29.8 ± 9.9 mg/day of 6-MP equivalent. However, all patients were identified with the wild type of TPMT genotype. There was no significant difference in the mean 6-TGN levels between patients in remission and no-remission group. The mean 6-TGN level was significantly higher in the once-daily administration group than three times-daily group.ConclusionThirty mg/day of 6-MP or 50 mg/day of AZA, once-daily oral administration in Japanese IBD patients was sufficient to achieve the therapeutic target level of 6-TGN in Europeans/Americans.     

A ferritin level > 50 μg/L is frequently consistent with iron deficiency

BackgroundThe British Society of Gastroenterology (BSG) suggests that a serum ferritin level ≤ 50 μg/L is still consistent with iron deficiency in the presence of coexistent pathology (inflammation, infection or malignancy), by implication excluding iron deficiency above this level. We aim to examine the validity of this cut-off level in three different groups of patients.MethodsWe used the soluble transferrin receptor/Log₁₀ferritin ratio (sTfR-F Index or Index) as a determinant of body iron stores. If the Index was equal or more than 2, the patients were considered iron deficient. Patients were considered iron replete if Index was ≤ 1. The data was prospectively collected over a period of 3 years. All patients had normocytic anaemia.ResultsWe collected data for 198 patients. Ninety-three had a sTfR-F Index ≥ 2 and 17 had Index ≤ 1. If a ferritin level ≤ 50 μg/L was used as the cut-off value for iron deficiency, the negative predictive value (NPV) of ferritin test was 22% and the positive predictive value (PPV) 100%; if the level is raised to 100 μg/L the NPV of ferritin test rose to 34.8% and the PPV was 97%.ConclusionPatients with normocytic anaemia who have ferritin levels above 50 μg/L should not automatically be considered to have adequate iron stores. We suggest that the integration of sTfR-F Index in the diagnostic workup of these patients can improve patient care.