title: High burden of iron deficiency and different types of anemia in inflammatory bowel disease outpatients in Scandinavia: A longitudinal 2-year follow-up study Ferric carboxymaltose in patients with heart failure and iron deficiency. Intravenous Iron Sucrose versus Oral Iron Supplementation for the Treatment of Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease—A Randomized, Controlled, Open-Label, Multicenter Study Intravenous iron therapy restores functional iron deficiency induced by infliximab. A Randomized, Open-Label, Non-Inferiority Study of Intravenous Iron Isomaltoside 1,000 (Monofer) Compared With Oral Iron for Treatment of Anemia in IBD (PROCEED) Iron Supplementation and Mortality in Incident Dialysis Patients: An Observational Study Ferric Maltol Is Effective in Correcting Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: Results from a Phase-3 Clinical Trial Program Recombinant human erythropoietin in patients with inflammatory bowel disease and refractory anemia: a 15-year single center experience. Age of red blood cells and transfusion in critically ill patients Transfusion strategies for acute upper gastrointestinal bleeding. A Novel Intravenous Iron Formulation for Treatment of Anemia in Inflammatory Bowel Disease: The Ferric Carboxymaltose (FERINJECT®) Randomized Controlled Trial The safety of intravenous iron dextran in hemodialysis patients. Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease. Efficacy of erythropoietin combined with enteral nutrition for the treatment of anemia in Crohn's disease: a prospective cohort study. Side-effects of oral iron therapy. A double-blind study of different iron compounds in tablet form. Safety and Efficacy of Total-Dose Infusion of Low Molecular Weight Iron Dextran for Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia Intravenous iron sucrose is superior to oral iron sulphate for correcting anaemia and restoring iron stores in IBD patients: A randomized, controlled, evaluator-blind, multicentre study FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Clinical update: intravenous iron for anaemia Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia Oral and intravenous iron treatment in inflammatory bowel disease: Hematological response and quality of life improvement
abstract: Abstract Objective . The prevalence of anemia in inflammatory bowel disease ( IBD ) has been broadly described . The recurrence , type and burden of anemia remain unenlightened . The primary objective was to describe this . The secondary objective was to evaluate the implementation of European guidelines . Material s and methods . This longitudinal follow-up study included 300 IBD out patients from six centers in Sc and inavia . Patients were enrolled in a research cohort , in which each center included 5 % of their IBD cohort . The study was prospect ively planned , while data were retrospectively collected . The burden of anemia was calculated as number of months with anemia . A Markov model was used to calculate the probabilities of transitioning between stages . The European guidelines were used as the st and ard for anemia management . Results . Anemia affected > 50 % of IBD out patients during the 2-year observation period . Totally , 20 % of the total observation time was spent in anemia . Over the 7200 months of observation , anemia was found in 1410 months . The most frequent type was combined anemia ( 63 % ) . Combined anemia covers both anemia of chronic disease ( ACD ) and iron-deficiency anemia ( IDA ) . Pure ACD was present in 21 % of burden time , while pure IDA was present in 16 % of burden time . The European guidelines have mainly been implemented . Conclusion . Anemia affected a majority of the IBD out patients . One in five months , the patients were anemic . Anemia related to inflammation dominated the different types of anemia . Pure IDA was found in for 16 % . These findings , despite a fair implementation of guidelines BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) OBJECTIVES : Anemia is a frequent complication in patients with inflammatory bowel disease ( IBD ) . The optimal route for iron supplementation to replenish iron stores has not been determined so far . We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia ( IDA ) in patients with IBD . METHODS : A r and omized , prospect i ve , open-label , multicenter study was performed in 46 patients with anemia and transferrin saturation ≤20 % and /or serum ferritin concentrations ≤20 μg/L. The intravenous group received a single dose of iron sucrose of 7 mg iron/kg body weight , followed by five 200 mg infusions for the following 5 wks . The oral group received iron sulfate 100–200 mg per day for 6 wks . RESULTS : While a comparable increase in hemoglobin was observed for both administration routes ( median increase 0.25 g/L in the intravenous group vs 0.21 g/L in the oral group ) , only iron sucrose led to a rise in serum ferritin concentrations . Intractable gastrointestinal adverse events caused permanent study drug discontinuation in five patients ( 20.8 % ) receiving iron sulfate , whereas only one patient ( 4.5 % ) had to be withdrawn because of side effects due to iron sucrose . CONCLUSIONS : Although being equal in short-term efficacy and overall tolerability our results suggest a better gastrointestinal tolerability for iron sucrose . Larger trials are m and atory to prove a possible advantage of iron sucrose in short- and long-term efficacy as well as in tolerability over iron sulfate in the management of IDA in IBD BACKGROUND AND AIMS Infliximab ( IFX ) and iron sucrose ( FeS ) are of high value in inflammatory bowel disease ( IBD ) . We aim ed to assess the relative role of both therapies in IBD related anaemia and their safety when used in combination . METHODS IBD patients with anaemia receiving a first series of FeS infusions in addition to IFX were prospect ively followed . We investigated serum kinetics of erythropoietin ( EPO ) , soluble transferrin receptors ( sTFRs ) and vascular endothelial growth factor ( VEGF ) . RESULTS Data analysis included 87 patients of whom 49.4 % achieved the target Hb level of 12.0 g/dL.  IFX result ed in a significant increase of EPO and sTFR compared to baseline pre-IFX levels ( p=0.029 and p=0.005 respectively ) and after a 12-week combined FeS and IFX treatment , EPO and sTFR levels dropped significantly compared to pre-FeS levels ( p<0.001 for both ) . Infusion related adverse events were recorded in 2 IFX treated patients ( 2.3 % , 0.7 % of the infusions ) and were mild . Disease activity and quality of life were not affected . CONCLUSIONS In anaemic IBD patients treated with IFX  , combined administration of FeS is safe . Infliximab significantly increases serum EPO and sTFR levels result ing in an increased functional iron deficiency , which is restored after combined treatment with I.V. iron sucrose OBJECTIVES : In the largest head-to-head comparison between an oral and an intravenous ( IV ) iron compound in patients with inflammatory bowel disease ( IBD ) so far , we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia ( IDA ) . METHODS : This prospect i ve , r and omized , comparative , open-label , non-inferiority study was conducted at 36 sites in Europe and India . Patients with known intolerance to oral iron were excluded . A total of 338 IBD patients in clinical remission or with mild disease , a hemoglobin ( Hb ) < 12 g/dl , and a transferrin saturation ( TSAT ) < 20 % were r and omized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula ( 225 patients ) or oral iron sulfate 200 mg daily ( equivalent to 200 mg elemental iron ; 113 patients ) . An interactive web response system method was used to r and omize the eligible patient to the treatment groups . The primary end point was change in Hb from baseline to week 8 . Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of −0.5 g/dl . The secondary end points , which tested for superiority , included change in Hb from baseline to weeks 2 and 4 , change in s-ferritin , and TSAT to week 8 , number of patients who discontinued study because of lack of response or intolerance of investigational drugs , change in total quality of life ( QoL ) score to weeks 4 and 8 , and safety . Exploratory analyses included a responder analysis ( proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks ) , the effect of regional differences and total iron dose level , and other potential predictors of the treatment response . RESULTS : Non-inferiority in change of Hb to week 8 could not be demonstrated . There was a trend for oral iron sulfate being more effective in increasing Hb  than iron isomaltoside 1,000 . The estimated treatment effect was −0.37 ( 95 % confidence interval ( CI ) : −0.80 , 0.06 ) with P=0.09 in the full analysis set ( N=327 ) and −0.45 ( 95 % CI : −0.88 , −0.03 ) with P=0.04 in the per protocol analysis set ( N=299 ) . In patients treated with IV iron isomaltoside 1,000 , the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 ( 95 % CI : 18.6 , 78.8 ) with P=0.002 , whereas the mean change in TSAT was lower with an estimated treatment effect of −4.4 ( 95 % CI : −7.4 , −1.4 ) with P=0.005 , compared with patients treated with oral iron . No differences in changes of QoL were observed . The safety profile was similar between the groups . The proportion of responders with Hb ≥2 g/dl ( IV group : 67 % ; oral group : 61 % ) were comparable between the groups ( P=0.32 ) . Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of > 1,000 mg IV . Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein ( CRP ) . CONCLUSIONS : We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study . Based on the dose – response relationship observed with the IV iron compound , we suggest that the true iron dem and of IV iron was underestimated by the Ganzoni formula in our study . Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD Background Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting . Methods In our observational single-center cohort study ( INVOR study ) we prospect ively studied 235 incident dialysis patients . Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality , cardiovascular and sepsis-related mortality . Furthermore , the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein ( CRP ) levels ( < 0.5 mg/dL ) and elevated CRP levels ( ≧0.5 mg/dL ) was evaluated by using non-linear P-splines to allow flexible modeling of the association . Results One hundred and ninety-one ( 81.3 % ) patients received intravenous iron , 13 ( 5.5 % ) patients oral iron , whereas 31 ( 13.2 % ) patients were never supplemented with iron throughout the observation period . Eighty-two ( 35 % ) patients died during a median follow-up of 34 months , 38 patients due to cardiovascular events and 21 patients from sepsis . Baseline CRP levels were not different between patients with and without iron supplementation . However , baseline serum ferritin levels were lower in patients receiving iron during follow up ( median 93 vs 251 ng/mL , p<0.001 ) . Iron supplementation was associated with a significantly reduced all-cause mortality [ HR ( 95%CI ) : 0.22 ( 0.08–0.58 ) ; p = 0.002 ] and a reduced cardiovascular and sepsis-related mortality [ HR ( 95%CI ) : 0.31 ( 0.09–1.04 ) ; p = 0.06 ] . Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality , whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality . Conclusions Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients . While serum ferritin levels up to 800 ng/mL appear to be safe , higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation Background : Iron deficiency anemia ( IDA ) is frequently seen in inflammatory bowel disease . Traditionally , oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation . This multicenter phase-3 study tested the efficacy and safety of ferric maltol , a complex of ferric ( Fe3 + ) iron with maltol ( 3-hydroxy-2-methyl-4-pyrone ) , as a novel oral iron therapy for IDA . Methods : Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn 's disease , mild-to-moderate IDA ( 9.5–12.0 g/dL and 9.5–13.0 g/dL in females and males , respectively ) , and documented failure on previous oral ferrous products received oral ferric maltol capsules ( 30 mg twice a day ) or identical placebo for 12 weeks according to a r and omized , double-blind , placebo-controlled study design . The primary efficacy endpoint was change in hemoglobin ( Hb ) from baseline to week 12 . Safety and tolerability were assessed . Results : Of 329 patients screened , 128 received r and omized therapy ( 64 ferric maltol-treated and 64 placebo-treated patients ) and comprised the intent-to-treat efficacy analysis : 55  ferric maltol patients ( 86 % ) and 53 placebo patients ( 83 % ) completed the trial . Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4 , 8 , and 12 : mean ( SE ) 1.04 ( 0.11 ) g/dL , 1.76 ( 0.15 ) g/dL , and 2.25 ( 0.19 ) g/dL , respectively ( P < 0.0001 at all time-points ; analysis of covariance ) . Hb was normalized in two-thirds of patients by week 12 . The safety profile of ferric maltol was comparable with placebo , with no impact on inflammatory bowel disease severity . Conclusions : Ferric maltol provided rapid clinical ly meaningful improvements in Hb and showed a favorable safety profile , suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease AIM OF THE STUDY To describe our 15-year experience on the patients ' response and safety to the use of EPO in IBD patients with refractory anemia . PATIENTS - METHODS Single 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 . RESULTS In total 820 IBD files were review ed 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 . CONCLUSIONS In anemic IBD patients who are refractory to I.V. iron monotherapy  , administration of EPO significantly improved peripheral blood parameters with safety . Prospect i ve controlled trials are needed to confirm positive patients ' response to EPO and identify those patients who are more likely to benefit Red blood cells ( RBC ) storage facilitates the supply of RBC to meet the clinical dem and for transfusion and to avoid wastage . However , RBC storage is associated with adverse changes in erythrocytes and their preservation medium . These changes are responsible for functional alterations and for the accumulation of potentially injurious bioreactive substances . They also may have clinical ly harmful effects especially in critically ill patients . The clinical consequences of storage lesions , however , remain a matter of persistent controversy . Multiple retrospective , observational , and single-center studies have reported heterogeneous and conflicting findings about the effect of blood storage duration on morbidity and /or mortality in trauma , cardiac surgery , and intensive care unit patients . Describing the details of this controversy , this review not only summarizes the current literature but also highlights the equipoise that currently exists with regard to the use of short versus current st and ard ( extended ) storage duration red cells in critically ill patients and supports the need for large , r and omized , controlled trials evaluating the clinical impact of transfusing fresh ( short duration of storage ) versus older ( extended duration of storage ) red cells in critically ill patients BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial . We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy . METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and r and omly assigned 461 of them to a restrictive strategy ( transfusion when the hemoglobin level fell below 7 g per deciliter ) and 460 to a liberal strategy ( transfusion when the hemoglobin fell below 9 g per deciliter ) . R and omization was stratified according to the presence or absence of liver cirrhosis . RESULTS A total of 225 patients assigned to the restrictive strategy ( 51 % ) , as compared with 61 assigned to the liberal strategy ( 14 % ) , did not receive transfusions ( P<0.001 ) [corrected].The probability of survival at 6 weeks was higher in the restrictive- strategy group than in the liberal- strategy group ( 95 % vs. 91 % ; hazard ratio for death with restrictive strategy , 0.55 ; 95 % confidence interval [ CI ] , 0.33 to 0.92 ; P=0.02 ) . Further bleeding occurred in 10 % of the patients in the restrictive- strategy group as compared with 16 % of the patients in the liberal- strategy group ( P=0.01 ) , and adverse events occurred in 40 % as compared with 48 % ( P=0.02 ) . The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer ( hazard ratio , 0.70 ; 95 % CI , 0.26 to 1.25 ) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease ( hazard ratio , 0.30 ; 95 % CI , 0.11 to 0.85 ) , but not in those with cirrhosis and Child-Pugh class C disease ( hazard ratio , 1.04 ; 95 % CI , 0.45 to 2.37 ) . Within the first 5 days , the portal-pressure gradient increased significantly in patients assigned to the liberal strategy ( P=0.03 ) but not in those assigned to the restrictive strategy . CONCLUSIONS As compared with a liberal transfusion strategy , a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding . ( Funded by Fundació Investigació Sant Pau ; Clinical Trials.gov number , NCT00414713 . ) BACKGROUND AIMS : Anemia is a common complication of inflammatory bowel diseases ( IBD ) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation , ferric carboxymaltose ( FeCarb ) , in comparison with oral ferrous sulfate ( FeSulf ) in reducing iron deficiency anemia ( IDA ) in IBD . METHODS : Two hundred patients were r and omized in a 2:1 ratio ( 137 FeCarb:63 FeSulf ) to receive FeCarb ( maximum 1,000 mg iron per infusion ) at 1-wk intervals until the patients ' calculated total iron deficit was reached or FeSulf ( 100 mg b.i.d . ) for 12 wk . The primary end point was change in hemoglobin ( Hb ) from baseline to week 12 . RESULTS : The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group , demonstrating noninferiority ( P = 0.6967 ) . Response ( defined as Hb increase of > 2.0 g/dL ) was higher for FeCarb at week 2 ( P = 0.0051 ) and week 4 ( P = 0.0346 ) . Median ferritin increased from 5.0 to 323.5 μg/L at week 2 , followed by a continuous decrease in the FeCarb group ( 43.5 μg/L at week 12 ) . In the FeSulf group , a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed . Treatment-related adverse events ( AEs ) occurred in 28.5 % of the FeCarb and 22.2 % of the FeSulf groups , with discontinuation of study medication due to AEs in 1.5 % and 7.9 % , respectively . CONCLUSIONS : FeCarb is effective and safe in  IBD-associated anemia  . It is noninferior to FeSulf in terms of Hb change over 12 wk , and provides a fast Hb increase and a sufficient refill of iron stores The treatment of anemia in hemodialysis patients is frequently hindered by the presence of suboptimal iron stores . Intravenous iron dextran is in common use to maintain iron stores in this population , but there are little published data regarding the incidence and type of adverse events . The purpose of this study was to evaluate the safety of this medication . Charts from four hemodialysis centers of all 573 patients treated with intravenous iron dextran ( INFeD ; Schein Pharmaceutical , Inc , Florham Park , NJ ) between July 1 , 1993 , and June 30 , 1995 , were studied . Twenty-seven patients ( 4.7 % ) had adverse reactions that were related to iron dextran . Four patients ( 0.7 % ) had reactions classified as serious ( one cardiac arrest ; three others required hospitalization ) . Ten patients ( 1.7 % ) had reactions classified as anaphylactoid . No patients died or developed permanent disability as a result of reactions . The most common adverse reactions included itching ( 1.5 % of patients ) and dyspnea or wheezing ( 1.5 % ) ; others included chest pain ( 1.0 % ) , nausea ( 0.5 % ) , hypotension ( 0.5 % ) , swelling ( 0.5 % ) , dyspepsia ( 0.5 % ) , diarrhea ( 0.5 % ) , skin flushing ( 0.3 % ) , headache ( 0.3 % ) , cardiac arrest ( 0.2 % ) , and myalgias ( 0.2 % ) . Five of all the reactions occurred during a test dose ; four of these were anaphylactoid . Several factors were studied as possible predictors of adverse reactions . A positive history of drug allergy ( odds ratio , 2.4 ; P = 0.03 ) and history of multiple drug allergy ( odds ratio , 5.5 ; P = 0.0004 ) were significant predictors of reactions . In summary , we found serious adverse reactions to be uncommon in hemodialysis patients treated with intravenous iron dextran .  Future prospect i ve studies will help confirm this finding BACKGROUND & AIMS Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases ( IBD ) . Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD . We performed a r and omized , placebo-controlled trial to determine if administration of ferric carboxymaltose ( FCM ) prevents anemia in patients with IBD and low levels of serum ferritin . METHODS We performed a single-blind , multicenter study of nonanemic patients who had completed the FERGIcor study .  Serum levels of ferritin were assessed every second month , and patients were given FCM ( total iron dose , 1181 ± 662 mg ; n = 105 ) or placebo ( n = 99 ) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months . Secondary end points included changes of quality of life , disease activity , results from laboratory tests , and adverse events . RESULTS Anemia recurred in 26.7 % of subjects given FCM and in 39.4 % given placebo . The time to anemia recurrence was longer in the FCM group ( hazard ratio , 0.62 ; 95 % confidence interval , 0.38 - 1.00 ; P = .049 ) . Markers of body levels of iron increased or remained at normal levels in subjects given FCM ( ferritin increased by 30.3 μg/L , transferrin saturation increased by 0.6 % ) but decreased in the group given placebo ( ferritin decreased by 36.1 μg/L , transferrin saturation decreased by 4.0 % ) . Changes in quality of life and disease activity were comparable between groups . Adverse events were reported in 59.0 % of the FCM group and 50.5 % of the placebo group , and serious adverse events were reported in 6.7 % and 8.1 % , respectively . CONCLUSIONS FCM prevents recurrence of anemia in patients with IBD , compared with placebo . Nevertheless , the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment BACKGROUND Anemia is a common and serious complication in patients with inflammatory bowel disease . The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin ( EPO ) combined with enteral nutrition ( EN ) in anemic Crohn 's disease ( CD ) patients , in terms of hemoglobin level , treatment success rate , adverse events , and predictor of this therapy . MATERIAL S AND METHODS We performed a prospect i ve study in CD patients . On the basis of hemoglobin level , all enrolled patients were divided into anemic and nonanemic groups . The anemic group was further divided into EPO and non-EPO subgroups , depending on whether EPO was prescribed . Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment . RESULTS In total , 109 patients ( 49 nonanemic and 60 anemic , including 38 EPO and 22 non-EPO ) were included . The prevalence of anemia in CD was 55.05 % . Age , disease behavior , Crohn 's Disease Activity Index scores , C-reactive protein , and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups . An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group . Treatment success rate was 63.16 % in the EPO group , whereas none of patients achieved treatment success in the non-EPO group . CONCLUSION EPO combined with EN can improve the hemoglobin level in anemic CD patients SUMMARY Using a double-blind and placebo technics , the side-effects of tablets containing different iron compounds were compared in 1496 subjects . Three separate series , all of which included placebo and ferrous sulphate tablets were studied . The agreement between the results obtained in different series was very good . Ferrous sulphate , ferrous gluconate , ferrous fumarate , and ferrous glycine sulphate had almost the same incidence and type of side-effects . The incidence was significantly higher than when placebo tablets were given Background Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease ( IBD ) .  Low molecular weight ( LMW ) iron dextran has the ability to administer the patient ’s total iron requirement in a single infusion . Aims The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD . Methods Fifty IBD patients ( 27 female , 35 Crohn ’s disease , 15 ulcerative colitis ) were included in the study . Mean ± st and ard deviation ( SD ) hemoglobin and ferritin levels before the infusion were 9.88 ± 1.42 g/dl and 13.9 ± 10.9 ng/ml , respectively . A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit . Several clinical and laboratory parameters were measured before and on week 4 after infusion . Results Four patients ( 8 % ) developed adverse reactions during the test infusion and did not receive the total-dose infusion . Only one patient developed an allergic reaction during the total-dose infusion . In the remaining 45 patients , the mean ± SD iron dose that was given was 1,075 ± 269 mg . The mean ± SD elevation of hematocrit and hemoglobin on week 4 was 4.9 ± 1.9 % and 1.7 ± 0.8 g/dl , respectively . Hematopoietic response was observed in 23 of 45 patients ( 51.1 % ) . Conclusion Total parenteral iron replacement with LMW iron dextran is an easy , safe , and effective alternative method for treating iron deficiency anemia in IBD . Harmless adverse reactions may develop in a minority of patients Background : In patients with inflammatory bowel disease , oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease , and to increase disease activity Purpose Inflammation-induced anemia is frequent among critically ill patients and can be aggravated by true iron deficiency ( ID ) result ing from blood losses . The serum hepcidin level controls the availability of iron for erythropoiesis , and its determination offers new perspectives for the diagnosis of ID in the presence of inflammation . We conducted a prospect i ve observational study to determine the cutoff value and diagnostic accuracy of hepcidin levels for detecting ID in critically ill anemic patients . Methods Patients suffering from anemia ( hemoglobin < 100 g/l ) and expected to stay for more than 7 days in intensive care had weekly determinations of hematological and iron parameters , including hepcidin levels ( ELISA test ) . The  iron status  for each set of measures was determined by the consensus of three experts , blinded to hepcidin values . Results Of 51 patients ( 36 male/15 female ) , 5 had ID at inclusion , while 8 developed ID during their stay . A total of 128 iron profiles were analyzed . Median hepcidin levels were 80.5 ( 0.05–548.3 ) and 526.6 ( 246.7–891.4 ) µg/l for ID and non-ID profiles , respectively . The onset of ID during the ICU stay led to a progressive decline in hepcidin levels , whereas a persistent inflammatory profile remained associated with high hepcidin concentrations . The optimal threshold for serum hepcidin for ID diagnosis was assessed by building 100 ROC curves using a resampling method and found at 129.5 µg/l [ 95 % CI = ( 115.5–143.4 ) ] . Conclusions Hepcidin levels may be suppressed by ID even in case of inflammation . Serum hepcidin of 129.5 µg/l was the most accurate threshold for ID diagnosis in critically ill patients with anemia Objective . Patients with inflammatory bowel disease ( IBD ) often have low iron stores or anaemia . There is controversy about whether iron should be supplemented orally or intravenously ( i.v . ) . The purpose of this study was to investigate whether treatment with intravenous iron is superior to treatment with oral iron . The primary end-points were response and remaining anaemia at the end of treatment ( EOT ) . Material and methods . Ninety-one patients with IBD and anaemia ( B-Hb < 115 g/L ) were r and omized to oral iron sulphate ( n=46 ) or intravenous iron sucrose ( n=45 ) treatment for 20 weeks . Results . Forty-three patients in the intravenous iron group completed the study compared to 35 patients in the oral iron group ( p=0.0009 ) . Only 22 patients ( 48 % ) tolerated the prescribed oral dose , and 52 % reduced the dose or withdrew from treatment because of poor tolerance . At EOT , 47 % patients in the oral iron group increased their B-Hb by ≥20 g/L , compared with 66 % in the intravenous iron group ( p=0.07 ) . In the oral iron group , 41 % still had anaemia versus 16 % of the patients in the intravenous iron group ( p=0.007 ) , and 22 % versus 42 % reached their reference B-Hb level ( p=0.04 ) . Treatment with intravenous iron sucrose improved iron stores faster and more effectively than oral iron ( p=0.002 ) . Under treatment with intravenous iron , 74 % of the patients had no anaemia and normal S-ferritin levels ( > 25 µg/L ) at EOT compared with 48 % of patients receiving oral iron ( p=0.013 ) . Conclusions . Treatment with intravenous iron sucrose is effective , safe , well tolerated and superior to oral iron in correcting haemoglobin and iron stores in patients with IBD BACKGROUND & AIMS Iron deficiency anemia ( IDA ) is common in chronic diseases and intravenous iron is an effective and recommended treatment . However , dose calculations and inconvenient administration may affect compliance and efficacy . We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen ( FCM ) with individually calculated iron sucrose ( IS ) doses in patients with inflammatory bowel disease ( IBD ) and IDA . METHODS This r and omized , controlled , open-label , multicenter study included 485 patients with IDA ( ferritin < 100 μg/L , hemoglobin [ Hb ] 7 - 12 g/dL [ female ] or 7 - 13 g/dL [ male ] ) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries . Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron , or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron . Primary end point was Hb response ( Hb increase ≥ 2 g/dL ) ; secondary end points included anemia resolution and iron status normalization by week 12 . RESULTS The results of 240  FCM-treated and 235 IS-treated patients were analyzed . More patients with FCM than IS achieved Hb response ( 150 [ 65.8 % ] vs 118 [ 53.6 % ] ; 12.2 % difference , P = .004 ) or Hb normalization ( 166 [ 72.8 % ] vs 136 [ 61.8 % ] ; 11.0 % difference , P = .015 ) . Both treatments improved quality of life scores by week 12 . Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience . Deviations from scheduled total iron dosages were more frequent in the IS group . CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance , as well as a good safety profile , compared with the Ganzoni-calculated IS dose regimen For nearly half a century , parenteral iron has been considered dangerous and for use only in extreme situations and when oral iron was not tolerated . This proscription was based largely on poorly characterised and infrequent anaphylactoid reactions to the high-molecular-weight dextran preparation ( Imferon ) that for most of this time was the only product available . Moreover , when parenteral iron was necessary , the recommended approach was small intramuscular doses ( ≤100 mg ) , even after intravenous administration of the total iron defi cit as a single dose or as repetitive boluses was shown to be as safe and eff ective as the intramuscular route . This mindset persists despite the subsequent introduction of low-molecular-weight iron dextran and two iron salt preparations , ferric gluconate and iron saccharate ( the latter is also known as iron sucrose ) , all of which are associated with fewer serious adverse events than the high-molecular-weight dextran . The introduction of recombinant erythropoietin for dialysis patients was associated with the development , in some individuals , of functional iron defi ciency that limited effi cacy . Intravenous iron , unlike oral iron , improves erythropoietic response in dialysis patients , and is now routinely used . The discovery of the iron regulatory peptide , hepcidin , has improved our underst and ing of the anaemia of chronic infl ammatory states , including cancer . Hepcidin is upregulated in these conditions , result ing in increased synthesis by the liver . Hepcidin inhibits iron transport across cell membranes , which decreases the accessibility of storage iron and gastrointestinal absorption of dietary iron , leading to an increased frequency of iron-restricted erythropoiesis , especially during therapy with recombinant erythropoietin . The most frequent laboratory fi ndings during the anaemia of chronic infl ammation are hypoferraemia and a low percent transferrin saturation , although these fi ndings are not always present . The increasing use of recombinant erythropoietin to treat anaemia in patients with chronic diseases has exp and ed the population of patients with functional iron defi ciency and increased interest in safe rational approaches to parenteral iron therapy . There is mounting evidence that anaemic patients with cancer undergoing chemotherapy and receiving  recombinant erythropoietin respond better when parenteral iron is administered . This benefi t is independent of baseline iron variables , such as ferritin , low percentage transferrin saturation , and stainable marrow haemosiderin , leaving the clinician in need of laboratory variables to reliably detect iron-restricted erythropoiesis in patients with infl ammatory illnesses and to predict improvement of erythropoietic response to parenteral iron in the setting of infl ammatory illness . Two new laboratory measures look promising : percent hypochromic red blood cells and reticulocyte haemoglobin content . These tests are reliable and accurate correlates of functional iron defi ciency . Although these investigations are not yet widely available , their use will probably exp and and guide identifi cation of functional iron defi ciency and rational intervention with parenteral iron . Currently , four parenteral iron preparations are available ( table ) . No r and omised trials have compared the safety and effi cacy of any of these agents . The largest retrospective review of dialysis experience suggests that most serious adverse events have been associated with the high-molecular-weight iron dextrans ( Imferon , which is no longer available and the current preparation , Dexferrum ) and are rare ( < 1:200 000 ) with the low-molecular-weight iron dextran or the two iron salts ( fi gure ) . Adverse event rates might be somewhat higher in patients with infl ammatory diseases in which immune-mediated drug reactions  may be observed more commonly than in dialysis patients . Some of the adverse clinical experience with parenteral iron is due to inappropriate supportive care . Myalgias , when they include chest and back discomfort , are mistakenly described as anaphylaxis , prompting Low – molecular – weight iron dextran Iron saccharate Ferric gluconate High – molecular – weight iron Levels of hepcidin , a major regulator of iron homeostasis , may identify patients with iron deficiency anemia ( IDA ) who will not respond to oral iron therapy . In this study , IDA patients underwent a 14‐day trial ( run‐in ) course of ferrous sulfate therapy . Nonresponders ( Hgb increase < 1 g/dL with 67 % compliance rate ) were r and omized to IV ferric carboxymaltose ( FCM ; two injections of 750 mg ) or further oral iron for 14 days . Screening hepcidin levels were 38.4 versus 11.3 ng/mL , P = 0.0002 in nonresponders versus responders to a trial of oral iron . Hepcidin of > 20 ng/mL , showed sensitivity of 41.3 % , specificity of 84.4 % , and positive predictive value of 81.6 % for predicting nonresponsiveness to oral iron . PPVs for ferritin > 30 ng/mL or transferrin saturation (TSAT)>15 % were 59.2 and 55 % , respectively . Negative predictive values for hepcidin , ferritin , and TSAT were 46.3 , 22.7 , and 19.7 , respectively . FCM versus oral iron showed Hgb increases of ≥1 gm/dL in 65.3 % versus 20.8 % ( P < 0.0001 ) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL ( P = 0.0025 ) , respectively . We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose . Nonresponse  to oral iron therapy does not rule out IDA , since two‐thirds of patients subsequently responded to intravenous iron . Am . J. Hematol . 88:97–101 , 2013 . © 2012 Wiley Periodicals , Background : The aim was to evaluate the efficacy and tolerance of oral and intravenous iron treatment in anemic inflammatory bowel disease ( IBD ) patients , considering both hematological and quality ‐of‐life outcomes . Methods : We performed a prospect i ve multicenter study in IBD patients with iron deficiency anemia . Patients having hemoglobin > 10 g/dL were prescribed oral ferrous sulfate . If hemoglobin < 10 g/dL , intravenous ( sucrose ) iron was administered . Oral iron‐intolerant patients were changed to intravenous treatment .  Clinical ( Truelove/Harvey – Bradshaw ) , hematological ( response defined as hemoglobin normalization ) , and quality ‐of‐life ( shortened CCVEII‐9 question naire ) evaluations were performed at baseline and at 3 and 6 months . Results : 100 IBD patients ( 59 Crohn 's disease , 41 ulcerative colitis ) were included . Mean basal hemoglobin levels were 10.8 ± 1.3 g/dL ( range , 6.6–12.9 ) . Seventy‐eight patients received oral treatment and 22 intravenous iron .  Hemoglobin normalization was achieved in 86 % of patients : 89 % with oral , and 77 % with intravenous iron . An IBD activity increase was not demonstrated in any patient . Four patients ( 5.1 % ) showed oral iron intolerance leading to discontinuation of treatment . No adverse events were reported for intravenous iron  . Hemoglobin correlated with CCVEII‐9 ( P < 0.001 ) . The CCVEII‐9 score increased in patients who normalized hemoglobin levels in 3 months ( from 58 ± 9 to 73 ± 10 ) or 6 months ( 54 ± 9 , 68 ± 12 , and 74 ± 10 ) ( P < 0.001 ) . Conclusions : Oral iron treatment is effective and well tolerated in most IBD patients , and does not exacerbate the symptoms of the underlying IBD . Intravenous iron , on the other h and , is an effective and safe alternative treatment for iron deficiency anemia in more severely anemic or intolerant patients . Anemia correction with iron treatment is associated with a relevant improvement in the patients ' quality of life . ( Inflamm Bowel Dis 2009
target: However , in patients with IBD flares and inadequate responses to or side effects with oral preparations , intravenous iron supplementation is the therapy of choice .
  Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD , and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics .
  Based on the data presented , oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency  anemia unless such patients are intolerant or have an inadequate response , whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron
background: Abstract Anemia is the most frequent complication of inflammatory bowel disease ( IBD ) , but anemia , mostly due to iron deficiency , has long been neglected in these patients .
  The aim was to briefly present the pathophysiology , followed by a balanced overview of the different forms of iron replacement available , and subsequently , to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD .