Evidence Of Iron Deficiency Research Articles

Performance Characteristics of Percentage of Hypochromic Red Cells in the Detection of Latent Iron Deficiency in Women with Menometrorrhagia

BACKGROUND
 Menometrorrhagia is a common cause of iron deficiency anemia (IDA) in women of reproductive age group. Latent iron deficiency (LID) is a precursor stage of IDA in which there is evidence of iron deficiency without anemia. LID causes cognitive impairment, impaired immunity and reduced work capacity which can be corrected by iron supplementation. Conventional biochemical and hematological parameters have limitations in the diagnosis of LID. This study was done to assess the performance characteristics of percentage of hypochromic red cells (% HYPO) in the detection of LID in women with menometrorrhagia.
 METHODS
 This study was done on 226 women attending the Gynaecology OP clinic of our institution, of which 183 had menometrorrhagia, and the remaining being controls. After testing for conventional hematological indices and serum ferritin, the subjects were divided into 3 groups: a LID group, an IDA group, and a control group without iron deficiency. ROC curve analysis was performed to assess % HYPO and other conventional hematological parameters in identifying LID.
 RESULTS
 Most hematological indices were within normal ranges in LID population, thus limiting their utility. The AUC for % HYPO in LID population was 0.736 with an optimum cut-off of 8.7 corresponding to a sensitivity and specificity of 62.3 and 76.74 respectively.
 CONCLUSIONS
 % HYPO is a sensitive, specific, fast, cheap, and practical and thus serves as a better predictive marker than conventional biochemical and hematological parameters in the detection of LID.

Iron Status of Preadolescents Without Clinical Pallor Attending a Tertiary Care Hospital in South India- A Cross-Sectional Analytical Study.

To determine the prevalence of Iron Deficiency (ID) in children without clinical pallor using serum ferritin and the new parameters, soluble transferrin receptor (sTfR) & the ratio of sTfR/log10 serum ferritin (sTfR-F index), as suggested by WHO. Also to assess whether these new parameters could individually predict the presence of ID. Consecutive 230 healthy children aged 9-11 y without clinical pallor underwent estimation of Hemoglobin (Hb), C-Reactive Protein (CRP), serum ferritin, sTfR, and sTfR-F index levels in their blood. The abilities of the sTfR and sTfR-F index in predicting ID were determined by comparing with the gold standard (normal CRP and less serum ferritin), plotting Receiver-operating characteristic (ROC) curve, and noting the area under the curve (AUC). The blood reports of 114 boys and 106 girls (total=220) were available for analysis. Overall, 57 (31 girls, 26 boys) children had ID; among children with low CRP, 45 had ID, as suggested by low serum ferritin levels. Among children with high CRP, 12 had evidence of ID as evidenced by elevated sTfR and/or sTfR-F index. The positive predictive values of both sTfR and sTfR-F were low (32.9% and 35.9%, respectively) than the negative predictive values (85.6% and 95.3%, respectively). The proportion of children identified to have ID using serum ferritin, sTfR, and sTfR-index was 25.9%. sTfRand/or sTfR-F index are unlikely to be ideal individual predictors of ID.

Iron status in patients with burn anaemia.

The iron status of burn patients is poorly understood, limited by difficulty interpreting conventional iron studies in the context of the acute phase response triggered by critical illness. The aim of this study was to evaluate the iron status of patients with burn anaemia using recent post-operative guidelines. This retrospective cohort study utilised data collected from records for adult patients admitted to the Royal Brisbane and Women's Hospital with burns to at least 15% TBSA. Rates of iron deficiency, defined as ferritin<100µg/L or ferritin 100-300µg/L with transferrin saturation<20%, and low iron availability, defined as transferrin saturation<20%, were calculated. Of 60 included patients (90% male), 16 (27%) underwent iron studies. 11 (18%) were treated with intravenous iron. Iron studies showed that five (31%) patients had evidence of iron deficiency, and ten out of 12 (83%) had evidence of reduced iron availability. Two patients (40%) with evidence of iron deficiency were not treated with intravenous iron. Application of recent guidelines for interpretation of conventional iron studies in patients with inflammatory states may improve the identification of iron deficiency in burn patients. Iron deficiency may be an under-recognised and under-treated contributor to burn anaemia.

Bone marrow iron scoring in healthy and clinically ill dogs with and without evidence of iron‐restricted erythropoiesis

There are few reports in dogs that have evaluated the utility of semi-quantitative scoring of bone marrow iron stores in conjunction with reticulocyte hemoglobin (CHr) to identify iron-restricted erythropoiesis due to absolute iron deficiency or iron sequestration. An established system for scoring iron stores in human bone marrow samples was applied to dogs. The objectives were to evaluate interobserver agreement (Κω ), determine marrow iron scores in dogs without detectable hematologic abnormalities, and assess combined interpretation of iron scores and CHr to evaluate for iron-restricted erythropoiesis. Four blinded observers independently scored iron in 139 Prussian blue-stained canine marrow samples from 0 (none) to 6 (very heavy), including healthy controls (n = 12), clinically ill dogs with (n = 100) and without (n = 16) detectable hematologic abnormalities, and dogs with experimental nutritional iron deficiency (n = 11). Additional medical record data were available for 118 dogs to evaluate for other evidence of iron deficiency (abnormal CHr, RBC indices, serum iron variables, external blood loss, or nutritional deficiencies). Mean Κω was 0.69 (substantial agreement) for all samples but was 0.44 (moderate agreement) for samples with iron scores <3, indicating distinguishing scores 0-2 may not be reliable. Dogs without detectable hematologic abnormalities had scores from 3-5. Dogs with scores <3 and decreased CHr often had more indicators of iron deficiency vs dogs only having low iron scores or low CHr. Evaluation of dogs with marrow iron score <3 for external blood loss or nutritional deficiencies is likely clinically worthwhile, particularly if there is also decreased CHr.

Rationale and design of a randomised trial of intravenous iron in patients with heart failure

ObjectivesFor patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves symptoms, exercise capacity and may...

INFERR-Iron infusion in haemodialysis study: INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis\u2014a protocol for a prospective open-label blinded endpoint randomised controlled trial

BackgroundThe effectiveness of erythropoiesis-stimulating agents, which are the main stay of managing anaemia of chronic kidney disease (CKD), is largely dependent on adequate body iron stores. The iron stores are determined by the levels of serum ferritin concentration and transferrin saturation. These two surrogate markers of iron stores are used to guide iron replacement therapy. Most Aboriginal and/or Torres Islander Australians of the Northern Territory (herein respectfully referred to as First Nations Australians) with end-stage kidney disease have ferritin levels higher than current guideline recommendations for iron therapy. There is no clear evidence to guide safe and effective treatment with iron in these patients. We aim to assess the impact of intravenous iron treatment on all-cause death and hospitalisation with a principal diagnosis of all-cause infection in First Nations patients on haemodialysis with anaemia, high ferritin levels and low transferrin saturationMethodsIn a prospective open-label blinded endpoint randomised controlled trial, a total of 576 participants on maintenance haemodialysis with high ferritin (> 700 μg/L and ≤ 2000 μg/L) and low transferrin saturation (< 40%) from all the 7 renal units across the Northern Territory of Australia will be randomised 1:1 to receive intravenous iron polymaltose 400 mg once monthly (200 mg during 2 consecutive haemodialysis sessions) (Arm A) or no IV iron treatment (standard treatment) (Arm B). Rescue therapy will be administered when the ferritin levels fall below 700 μg/L or when clinically indicated. The primary outcome will be the differences between the two study arms in the risk of hospitalisation with all-cause infection or death. An economic analysis and several secondary and tertiary outcomes analyses will also be performed.DiscussionThe INFERR clinical trial will address significant uncertainty on the safety and efficacy of iron therapy in First Nations Australians with CKD with hyperferritinaemia and evidence of iron deficiency. This will hopefully lead to the development of evidence-based guidelines. It will also provide the opportunity to explore the causes of hyperferritinaemia in First Nations Australians from the Northern Territory.Trial registrationThis trial is registered with The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620000705987. Registered 29 June 2020.

Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials

BackgroundThe recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials.MethodsWe searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these.ResultsAltogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59–0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54–0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66–1.21); p = 0.47].ConclusionAdministration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.Graphic abstract

The relationship between anemia and Kt/V index in patients undergoing continuous ambulatory peritoneal dialysis and hemodialysis

Introduction: Anemia in end-stage renal disease (ESRD) can cause serious problems for patients. Objectives: The present study was conducted to investigate whether the type or adequacy of dialysis can affect the incidence of anemia in these patients. Patients and Methods: This cross-sectional study was conducted on 57 patients with ESRD, who were referred to Qaem and Imam Reza hospitals, Mashhad, Iran. The patients were divided into two groups of continuous ambulatory peritoneal dialysis (CAPD) (n=37 patients) and hemodialysis (n=20 patients). Patients had no laboratory evidence of iron deficiency or hyperparathyroidism. Enrolled patients were received vitamin B12 and folic acid too. Hemoglobin concentration of under 11 mg/dL was considered as anemia. Adequacy of dialysis was evaluated by Kt/V index (&gt;1.2 for hemodialysis and &gt;1.7 per week for peritoneal dialysis). We compared different factors in these two groups, including anemia and Kt/V, and evaluated their relationship. Results: Around 27% and 65% of the patients on CAPD and hemodialysis were anemic respectively (P=0.005). Adequacy of dialysis in CAPD was acceptable in 81.1% of the cases, while target Kt/V was achieved in 50% of the patients on hemodialysis. Dialysis adequacy was significantly higher in patients receiving CAPD (P=0.014). No significant correlation between the incidence of anemia and Kt/V in both types of dialysis was found (P&gt;0.05). Conclusion: Anemia was mostly observed in patients receiving hemodialysis as compared to CAPD. Regardless of the type of dialysis, adequacy of dialysis did not affect the incidence of anemia in any of the groups.

Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder characterised by progressive generalised dystonia and brain iron accumulation. We assessed whether the iron chelator deferiprone can reduce brain iron and slow disease progression. We did an 18-month, randomised, double-blind, placebo-controlled trial (TIRCON2012V1), followed by a pre-planned 18-month, open-label extension study, in patients with PKAN in four hospitals in Germany, Italy, England, and the USA. Patients aged 4 years or older with a genetically confirmed diagnosis of PKAN, a total score of at least 3 points on the Barry-Albright Dystonia (BAD) scale, and no evidence of iron deficiency, neutropenia, or abnormal hepatic or renal function, were randomly allocated (2:1) to receive an oral solution of either deferiprone (30 mg/kg per day divided into two equal doses) or placebo for 18 months. Randomisation was done with a centralised computer random number generator and with stratification based on age group at onset of symptoms. Patients were allocated to groups by a randomisation team not masked for study intervention that was independent of the study. Patients, caregivers, and investigators were masked to treatment allocation. Co-primary endpoints were the change from baseline to month 18 in the total score on the BAD scale (which measures severity of dystonia in eight body regions) and the score at month 18 on the Patient Global Impression of Improvement (PGI-I) scale, which is a patient-reported interpretation of symptom improvement. Efficacy analyses were done on all patients who received at least one dose of the study drug and who provided a baseline and at least one post-baseline efficacy assessment. Safety analyses were done for all patients who received at least one dose of the study drug. Patients who completed the randomised trial were eligible to enrol in a single-arm, open-label extension study of another 18 months, in which all participants received deferiprone with the same regimen as the main study. The trial was registered on ClinicalTrials.gov, number NCT01741532, and EudraCT, number 2012-000845-11. Following a screening of 100 prospective patients, 88 were randomly assigned to the deferiprone group (n=58) or placebo group (n=30) between Dec 13, 2012, and April 21, 2015. Of these, 76 patients completed the study (49 in the deferiprone group and 27 in the placebo group). After 18 months, the BAD score worsened by a mean of 2·48 points (SE 0·63) in patients in the deferiprone group versus 3·99 points (0·82) for patients in the control group (difference -1·51 points, 95% CI -3·19 to 0·16, p=0·076). No subjective change was detected as assessed by the PGI-I scale: mean scores at month 18 were 4·6 points (SE 0·3) for patients in the deferiprone group versus 4·7 points (0·4) for those in the placebo group (p=0·728). In the extension study, patients continuing deferiprone retained a similar rate of disease progression as assessed by the BAD scale (1·9 points [0·5] in the first 18 months vs 1·4 points [0·4] in the second 18 months, p=0·268), whereas progression in patients switching from placebo to deferiprone seemed to slow (4·4 points [1·1] vs 1·4 points [0·9], p=0·021). Patients did not detect a change in their condition after the additional 18 months of treatment as assessed by the PGI-I scale, with mean scores of 4·1 points [0·2] in the deferiprone-deferiprone group and of 4·7 points [0·3] in the placebo-deferiprone group. Deferiprone was well tolerated and adverse events were similar between the treatment groups, except for anaemia, which was seen in 12 (21%) of 58 patients in the deferiprone group, but was not seen in any patients in the placebo group. No patient discontinued therapy because of anaemia, and three discontinued because of moderate neutropenia. There was one death in each group of the extension study and both were secondary to aspiration. Neither of these events was considered related to deferiprone use. Deferiprone was well tolerated, achieved target engagement (lowering of iron in the basal ganglia), and seemed to somewhat slow disease progression at 18 months, although not significantly, as assessed by the BAD scale. These findings were corroborated by the results of an additional 18 months of treatment in the extension study. The subjective PGI-I scale was largely unchanged during both study periods, indicating that might not be an adequate tool for assessment of disease progression in patients with PKAN. Our trial provides the first indication of a decrease in disease progression in patients with neurodegeneration with brain iron accumulation. The extensive information collected and long follow-up of patients in the trial will improve the definition of appropriate endpoints, increase the understanding of the natural history, and thus help to shape the design of future trials in this ultra-orphan disease. European Commission, US Food and Drug Administration, and ApoPharma Inc.

PF500 A NEW FTL GENE MUTATION RESPONSIBLE FOR HYPOFERRITINEMIA WITHOUT IRON DEFICIENCY

Background:Serum ferritin (sFt), is widely considered the best test to assess iron deficiency, as it reflects tissue iron storage. A decrease in sFt is an early indicator of a lack of iron in the body and precedes the decrease of serum iron and the onset of iron deficiency anemia. We present an exceptional case of hypoferritinemia, without anemia or associated iron deficiency. Repeated injections of intravenous iron to the patient led to severe iron overload.Aims:Case report: A 34‐year‐old woman was referred to our Center for investigation of iron overload. She reported that three years ago a biological assessment to investigate asthenia revealed very low sFt (1 μg/L). The CBC showed no anemia nor microcytosis. The patient had previously received oral iron supplementation for 8 years because of this low sFt. She was given IV iron and received 18 injections in 15 months. Following these injections, ferritin normalized (69 μg/L), but transferrin saturation (TSat) was measured at 96%. The patient consulted a few months later for severe asthenia, anorexia, weight loss and dyspnoea and was hospitalized. Liver iron concentration (LIC) measured by MRI was 190 μmol/g (N &lt;36 μmol/g). The diagnosis of secondary haemochromatosis was given and phlebotomies were started. When we saw the patient for second opinion, she already had 9 phlebotomies. Iron parameters showed a SFt at 2 μg/L, serum iron at 31.48 μmol/L and TSat at 92%. Hemoglobin (Hb) levels were normal at 128 g/L with a MCV at 98 fL. Due to a poor clinical tolerance of the phlebotomies, oral iron chelation was proposed. The patient reported that her father, mother, two sisters, and one brother also had unexplained hypoferritinemia and had received iron supplementation.Methods:After informed written consent, Sanger sequencing of the 5’UTR and exon 1 of the FTL (ferritin light chain) gene and NGS analysis of a panel of genes involved in hereditary iron overload (BMP6, HAMP, HFE, HJV, SLC40A1, TRF2) were performed.Results:An undescribed mutation of the FTL gene (c.92A&gt; G or p.Y31C), was identified at the homozygous state. A mutation of the BMP6 gene (c: 337C&gt; G or p.Gln133Glu) in the heterozygous state was also observed. This already described mutation is associated with a decrease expression of hepcidin and is thought to promote iron overload. However, hepcidin was measured 3 times at normal values in our patient.Summary/Conclusion:The mutation identified in the FTL gene is localized in the region involved in L ferritin secretion. Two hypotheses could account for the hypoferritinemia presented by the patient. It could be a lack of serum secretion of the L‐ferritin chain, despite normal tissue iron stores, or a modification of the recognition site by the antibodies used for ferritin assays (immunological). In order to explore these hypotheses, a study of family segregation and different assay techniques for ferritin were investigated. In addition, the BMP6 gene mutation could have played an aggravating cofactor role, favouring the occurrence of acquired iron overload in this patient. This case illustrates the importance of a pragmatic attitude in the presence of any discrepancies among iron parameters. This isolated hypoferritinemia without anemia or other evidence of iron deficiency, was not an indication of IV iron treatment, which led to iron overload and serious complications in the patient.

Atypical Red Blood Cells Are Prevalent in California Sea Lion Pups Born during Anomalous Sea Surface Temperature Events.

To date, there is limited knowledge of the effects that abnormal sea surface temperature (SST) can have on the physiology of neonate pinnipeds. However, maternal nutritional deficiencies driven by alimentary restrictions would expectedly impact pinniped development and fitness, as an adequate supply of nutrients is essential for growth and proper functioning of all body systems, including red blood cell synthesis and clearance. Here, we investigated red blood cell morphology of California sea lion (CSL) pups from the San Benito Archipelago born during the 2014 and 2015 anomalously high SST events recorded in the northeastern Pacific Ocean. We examined whether atypical erythrocyte morphologies were more common in 2015, when the high SST event was more pronounced, and whether the stable isotope signature of pup fur, as an indicator of maternal feeding strategies, accounted for the number of atypical cells. Various atypical erythrocyte morphologies were more prevalent and more abundant than reference values. Evidence of iron deficiency was found in both years, and only pups born in 2014 showed evidence of active erythropoiesis. Microcytes and reticulocytes were more common in pups with higher isotopic δ13C and lower δ15N values, suggesting a probable relationship between maternal feeding strategies and the effect of climatic anomalies on red blood cell physiology of their pups. As developing pinnipeds require increased oxygen storage capacity for diving and foraging, the presence of atypical erythrocytes could be relevant to CSL pup fitness if the underlying cause is not reverted. This study is a first step to explore the effects that climatic alterations in the marine environment can have on the blood physiology of developing individuals.

Author response: Practice guideline summary: Treatment of restless legs syndrome in adults: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

We appreciate Dr. Sethi's emphasis on the often overlooked iron treatment of restless legs syndrome (RLS) in the comment on our article.1 The recommendation to treat patients with serum ferritin less than or equal to 75 μg/L was based on the reviewed placebo-controlled study showing significant RLS benefit and ferritin increase with ferrous sulfate 325 mg (65 mg iron) with vitamin C 100 mg dosed twice daily.2 As described in the full-length guideline,1 only oral iron studies where patients had evidence of iron deficiency were considered for the guideline, and oral iron is absorbed only in the context of low iron levels. An additional placebo-controlled study with no serum ferritin limit (average 135 μg/L) showed no benefit on RLS symptoms or ferritin increase,3 likely reflecting limited absorption of iron for ferritin over 75 μg/L and also limitations in precision secondary to sample size. Optimal iron supplementation strategies are still under investigation.4 Clonazepam data are described in the full guideline report supplement,1,5,6 with insufficient evidence to support an evidence-based recommendation. Anecdotal evidence is subject to multiple types of bias and is insufficient to drive recommendations under the 2004 American Academy of Neurology process.

Factors associated with anemia among Sri Lankan primary school children in rural North Central Province

BackgroundDespite interventions, childhood anemia is still a major public health problem in low and middle income countries. Purpose of the present study is to determine factors associated with anemia among rural primary school children in Sri Lanka, a country undergoing rapid socioeconomic changes.MethodsMulti stage cluster sampling was used to select 100 rural schools in NCP and a maximum of 50 children aged 60–131 months were enrolled from each school. Self-administered questionnaires were sent to parents. Anthropometric measurements and blood samples were obtained by trained investigators. Blood reports were analyzed in a commercial laboratory with external quality control measures.ResultsTotal of 4412 children were included in the analysis. A Multiple regression was performed for hemoglobin. Only 4.2% of the change in hemoglobin could be explained by the model. District (p > 0.001), age (p > 0.001), timing of warm treatment(p = 0.026) and BMI for age (p = 0.002) uniquely contributed 1.12%, 1.19%, 0.13% and 0.26% to change in hemoglobin level respectively whereas, sex, monthly family income and frequency of meat and green leaf consumption didn’t contribute significantly.Peripheral blood film analyses were available for 146 anemic children. Blood film was reported as normal in 19.9% while evidence of iron deficiency (18.5%), early iron deficiency (32.5%) and thalassemia trait with iron deficiency (29.5%) were reported in the rest.Serum ferritin level was available for 417 children with hemoglobin less than 12 g/dl. Mean ferritin level was 63.7 microgram/l. Only 0.5% had depleted iron stores. A multiple regression was performed for serum ferritin and R2 was 0.123 (p < 0.001). Area under the curve for serum ferritin and anemia was 0.436.ConclusionAnemia among rural primary school children in NCP cannot be well explained by routinely assessed socioeconomic characteristics which mainly provide clues to access for food. Commonly used anemia related investigations have low validity in detecting and explaining anemia in this population. Since behavioral factors have been shown to affect nutrition of younger children in Sri Lanka, studying weather behaviors are related to anemia in primary school children is important. Possible etiologies including but not limited to nutritional deficiencies need to be studied further.

A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis.

Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p>0.05). The models performed similarly in the internal validation cohort. We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.

Aetiology of Preoperative Anaemia in Patients Undergoing Elective Cardiac Surgery—the Challenge of Pillar One of Patient Blood Management

Preoperative anaemia is common in patients undergoing cardiac surgery. Whilst there is a strong association with increased morbidity and mortality, it is currently unclear whether treatment of anaemia leads to patient benefit. This retrospective study aimed to determine the aetiology of preoperative anaemia in a cohort of patients undergoing elective cardiac surgery over two years at a tertiary hospital. Laboratory data obtained at the preoperative assessment clinic visit were assessed to stratify patients into four groups-iron deficiency anaemia (IDA), possible IDA, anaemia of chronic disease (ACD) and non-anaemic patients with low ferritin according to the 'Preoperative haemoglobin assessment and optimisation template' of the Australian Patient Blood Management (PBM) Guidelines. Of patients with preoperative anaemia, 23.1% had IDA, 6.6% had possible IDA and 70.3% had possible ACD. Of the patients with possible ACD, 30% had a ferritin <100 µg/l, representing limited iron stores or coexisting absolute iron deficiency in the setting of chronic disease. In addition, 46.2% of those with possible ACD had iron studies indicative of functional iron deficiency. Time between assessment and surgery was as little as one day in a third of patients and in only 7% was it more than seven days. Our findings indicate that about one-third of our patients with preoperative anaemia had evidence of iron deficiency, a potentially reversible cause of anaemia. In addition, a significant number had either limited iron stores that may render them iron deficient by surgery, or a functional iron deficiency.

PTU-014 Relationship between Ferritin/MCV and GI Pathology in Patients Referred from Primary Care with Iron Deficiency Anaemia: Abstract PTU-014 Table 1

Introduction Iron deficiency anaemia (IDA) is common with BSG guidance suggesting Gastrointestinal (GI) blood loss from colonic or gastric cancer, and malabsorption in coeliac disease are the most important causes. 1 Serum ferritin, microcytosis and hypochromia are the most sensitive markers for iron deficiency. 2 Our objective was to investigate the correlation between MCV/ferritin and GI pathology in patients with IDA by comparing GI pathology in patients with low ferritin versus normal ferritin; and in patients with microcytosis versus normocytosis. Methods Retrospective cohort study for consecutive patients who had undergone bi-directional endoscopy and/or GI imaging to investigate unexplained anaemia were included. Data was retrieved including Hb, MCV, folate, B12, co-morbidities and findings at endoscopy, histology and imaging were recorded. Patients with normal haemoglobin as per our laboratory’s cut off were excluded. Included patients were stratified according to serum ferritin and MCV into 2 groups (low/normal) for each marker. We used the cut-off concentration as per our local laboratory (10 µg/l for ferritin and 78 FL for MCV). The outcome assessed was any GI pathology found that may explain the IDA. Data was analysed including and excluding the diagnosis of gastritis/oesophagitis as possible GI causes of anaemia. Results 265 included patients (mean age: 68; range: 16–91 years old; 124 males and 141 females) had undergone GI investigations for IDA. Of these, 84 patients had low ferritin (31.6%) whereas 181 patients had normal ferritin. GI pathology excluding gastritis/oesophagitis occurred in 40 (47.6%) and 68 (37.5%) patients in low and normal ferritin group respectively. P = 0.12. Based on MCV, 96 patients had low MCV (36.2%) whereas 169 patients had normal MCV. GI pathology occurred in 38 patients in low MCV group (39.5%) and in 70 patients with normal MCV (41.4%), P = 0.76. No differences were noted upon including gastritis/oesophagitis. Conclusion There was no clinical or statistical difference in GI pathology in patients presenting with anaemia with or without evidence of iron deficiency. Although a significant number of patients had a GI workup despite no evidence of iron deficiency, the lesion pickup was similar in both groups. Therefore, our study demonstrates the MCV/ferritin might be sensitive markers for IDA but they don’t correlate with GI pathology. References 1 Gut 2011; 60 :1309e–1316. doi:10.1136/gut.2010.228874 2 Prevalence of hypochromia vs microcytosis in iron deficiency. Clin Lab Haematol 2000; 22 :79e80. Disclosure of Interest None Declared

Improving the management of iron deficiency in ambulatory heart failure patients

Based on clinical trial data patients with heart failure (HF) and evidence of iron deficiency should be offered intravenous (iv) iron with the aim of improving exercise capacity and symptoms....

Does moderate iron deficiency protect against childhood illness? A test of the optimal iron hypothesis in Tanzania.

To test the hypothesis that moderate iron deficiency among children is associated with lower likelihood of infection. We use data from a population representative cross sectional study of 1164 Tanzanian children aged 6-59 months from the Tanzania Demographic and Health Survey. Respondents' iron levels were assessed through serum transferrin receptor (sTfR) and anemia was assessed using hemoglobin. C-reactive protein (CRP) was used as a marker of infection. Nearly 25% of the children were categorized as normal (iron replete, non-anemic); 45% were IDE (low iron, non-anemic), 24% were classified as IDA (low iron, anemic), and 69 children (5.9%) were anemic but had no evidence of iron deficiency. IDE was not associated with a lower likelihood of elevated CRP compared to iron replete, non-anemic children; 45% of normal children had elevated CRP compared to 51% of IDE children (P = 0.10). IDA, by contrast, was associated with a higher likelihood of elevated CRP (68%, P < 0.001). These results were unchanged when child, maternal, and household controls were added to a logistic regression model. Our results do not support the optimal iron hypothesis as conventionally formulated. The fact that we did not find an effect where some other studies have may be due to differences in study design, sample (e.g., age), or the baseline pathogenic ecology. Alternatively, it may be more fruitful to investigate iron regulation as an allostatic system that responds to infections adaptively, rather than to expect an optimal pre-infection value.

S42 Effect of iron deficiency on oxygen transport in hypoxaemic patients: implications for haemodynamics and clinical management

BackgroundOxygen transport in the blood depends not only upon oxygen partial pressure (or saturation, SaO2), but also the concentration of haemoglobin to which oxygen binds, and blood volume in any...

Intravenous iron therapy in patients with heart failure. A double-edged sword

We read with interest the article of Beck-da-Silva et al., who recently concluded that intravenous (IV) iron seems to be superior over oral supplementation for improving functional capacity of heart failure patients [1]. Irrespective of the study design, involving comparison of functional outcomes between two different means of iron supplementation, we raise some clinical issues about the rationale underlying this investigation. According to the data published by Beck-da-Silva et al., the modest number of patients (n = 23) enrolled in this multicenter investigation had moderate anemia (i.e., hemoglobin concentration comprised between 90 and 120 g/L) but no evidence of iron deficiency, which would be the only plausible reason supporting whatever form of iron administration in thesepatients [1]. Themean ferritin value of the entire cohort of patients (132 ± 138 μg/L) was comprised within the current reference range of the healthy population for this parameter (i.e., 30– 300 μg/L for males and 15–200 μg/L for females, respectively). In particular, recent evidence shows that ferritin can effectively exclude iron deficiency anemia at a diagnostic threshold comprised between 40 and 70 μg/L [2]. No data were also provided about the values of mean corpuscular volume (MCV),mean cell hemoglobin (MCH)and redblood cell distributionwidth (RDW), which are all widely used parameters for establishing a diagnosis of iron deficiency [3,4]. It is well known, however, that anemia in up to two-third of patients with chronic heart failure is directly attributable to increased plasma volume and erythrocyte dilution rather than to a real reduction of red blood cell mass, thus generating a misleading impression of anemia [5]. Due to these drawbacks, there are several reasons that argue against the conclusion that IV iron should be considered a viable option in patients with heart failure and no evidence of iron deficiency. The leading targets of treating irondeficiencyanemia include restoring hemoglobin concentrations and red cell indices to normal, along with replenishing otherwise depleted iron stores [4]. Serum ferritin levels higher than 15 μg/L completely rule out iron deficiency anemia in the general adult population, and thereby preclude the need for iron supplementation [6]. On the other hand, it is noteworthy that the amount of physiological excretion of iron is negligible. Therefore, iron overload, especially when normal storage sites are full, is associated with large accumulation of this compound in body tissues and organs, thus causing a variety of adverse biological consequences. Iron is a vital compound for bacteria and other microorganisms, and it is generally assumed that iron supplementation predisposes to a greater risk of bacterial infections and infectious disease morbidity. Several bodies of evidence also suggest that iron triggers the generation of free radicals, which are involved in a kaleidoscope of chronic and severe disorders, including coronary atherosclerosis [7]. There is also a particular concern that iron supplementation in patients with heart failure may turn to be as a doubleedged sword, wherein it may induce transient functional improvement, but it may then chronically worsen cardiac perfusion, and even cause iron-overload cardiomyopathy and relatedmortality [8]. Additional undesirable effects that may be occasionally encountered in patients undergoing IV iron therapy include allergic or anaphylactic reactions [9]. Although the etiology is multifaceted and imperfectly understood, anemia is indeed frequent in patients with chronic heart failure [10], and has detrimental consequences on physical functioning and general health [11]. However, the convincing evidences gathered so far suggest that major caution should be used before recommending IV iron therapy in heart failure patients with no evidence of iron deficiency, wherein the potential benefits on functional capacity may be largely offset by serious side effects caused by iron overload.