Introduction Iron Deficiency Research Articles

Impact of various iron deficiency definitions on mortality risk in chronic heart failure across the spectrum of left ventricular ejection fraction spectrum

Abstract Introduction Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition. Purpose This study evaluates the prevalence of ID and its association with all-cause mortality and first hospitalization for HF, using current European Society of Cardiology (ESC) guidelines, transferrin saturation (TSAT) <20%, ferritin <100 ng/ml, and serum iron ≤13 μmol/L as ID criteria. Methods and Results Of 8587 new-onset HF patients registered in the Danish Heart Failure Registry from April 2003 to July 2021, we found varying ID prevalence (35.4% to 67%) based on different definitions. In heart failure with reduced ejection fraction (HFrEF) patients, irrespective of anemia, ID defined by TSAT <20% and serum iron ≤13 μmol/L was associated with all-cause mortality (non-anemic, HR: 1.42, 95% CI:1.22-1.64 and HR: 1.25, 95% CI: 1.1-1.43; anemic, HR: 1.22, 95% CI: 1.1-1.35 and HR: 1.26, 95% CI: 1.12-1.41, respectively) and first HF hospitalization (non-anemic, HR:1.41, 95% CI:1.23-1.62, HR: 1.33, 95% CI: 1.18-1.51; anemic, HR:1.27, 95% CI:1.12-1.45 and HR: 1.26, 95% CI:1.09-1.45, respectively). ID per ESC guidelines was only associated to mortality in non-anemic HFrEF (HR: 1.24, 95% CI:1.09-1.42) and first HF hospitalization in HFrEF, irrespective of anemia (non- anemic, HR:1.24, 95% CI:1.09-1.42; anemic, HR:1.35, 95% CI:1.2-1.52). No association was observed between the various definitions and outcomes in patients with heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction. Conclusion ID, when defined by TSAT <20% or serum iron ≤13 μmol/L, is associated with increased mortality and first hospitalization in HFrEF patients, regardless of anemia. Conversely, ID as per ESC guidelines is associated with mortality in non-anemic HFrEF patients and first hospitalization in HFrEF, irrespective of anemia status.Figure 1:Forest plot mortalityFigure 2:Forest plot hospitalization

Iron deficiency and all-cause mortality after myocardial infarction

Abstract Introduction Iron deficiency (ID) is commonly associated with cardiovascular diseases, including myocardial infarction (MI). However, the data on the clinical significance of ID in patients with MI are conflicting. This may be related to the use of various ID criteria. Purpose Our study aimed to compare the association of different ID criteria with all-cause mortality after MI. Methods Consecutive patients hospitalized at a large tertiary heart center for type 1 MI without previous history of coronary artery disease were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality during the follow-up. Results Of a cohort of 1,156 patients included (aged 64±12 years, 25% women), 194 (16.8%) died during the median follow-up of 3.4 years (IQR 626-1782 days). A total of 51,7% of post-MI patients had low iron levels (≤13 µmol/L), and 16,3% of them had iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95% CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and sTfR ≥3 mg/L (HR 2.56, 95% CI 1.64-3.99) were associated with an increased risk of mortality. This information provided additional predictive value to the GRACE score. No association between ferritin level and mortality was found. Compared to the model which contains iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95% CI 0.52-0.69) by reclassifying patients into a higher-risk group. Conclusion ID is common among patients with the first MI. The criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality, and should be evaluated in future interventional studies with intravenous iron therapy.Kaplan-Meier survival for iron levelsK-M survival for combined ID parameters

The efficacy of IV iron in anemic heart failure patients: a systemic review and meta-analysis of randomised controlled trials

Abstract Introduction Iron deficiency in the context of heart failure is a multifaceted concern, where the intricate interplay between diminished iron stores, impaired absorption mechanisms, and reduced recycled iron in the reticuloendothelial system adds a layer of complexity to patient management. Initial attempts to address this issue with oral iron treatments have been questioned due to its poor absorption. Intravenous iron therapy is now preferred, as it has been shown to reduce heart failure hospitalisations and cardiovascular mortality. However, there is a lack of randomised studies specifically focused on heart failure patients, highlighting the need for more targeted investigations. Purpose The aim of this review is to provide reliable evidence from published randomised controlled trials (RCTs) regarding the beneficial effect of IV iron in heart failure patients. Methods We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until December 2023. We included randomised controlled trials (RCTs) comparing the effect of IV iron in heart failure patients versus placebo. The primary outcomes were 6MWT mean change, ferritin concentration mean change, transferrin saturation mean change and worsening heart failure. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data. Results Twelve RCTs involving 6800 patients were included in the analysis. The overall effect on the measured primary outcomes was in favour of IV iron in terms of 6MWT mean change (MD= 34.45, 95% CI [ 29.58 to 39.31], P=<0.0001), ferritin concentration mean change (MD= 219.18, 95% CI [ 208.7 to 229.66], P=<0.0001), transferrin saturation mean change (MD= 9.77, 95% CI [ 8.14 to 1.39], P=<0.0001) and worsening heart failure (RR= 0.46, 95% CI [ 0.31 to 0.69], P=0.002). Conclusion The introduction of the IV iron therapy to heart failure patients showed a beneficial effect in terms of the measured haematological and cardiovascular metrics, which include 6MW test mean change, ferritin concentration mean change, and worsening heart failure.6MWT mean changeFerritin mean change

Serum transferrin concentration: a new prognostic biomarker in heart failure with reduced ejection fraction

Abstract Introduction Iron deficiency (ID) is a common comorbidity in patients with reduced heart failure (HFrEF), and is associated with poor clinical status and outcomes, but there is not enough data investigating serum transferrin concentration (STC) as a biomarker HFrEF to predict prognosis and mortality. Purpose We investigated relationship between STC at admission and all-cause mortality during follow-up in HFrEF. Methods We reviewed the medical data of 420 patients hospitalised in our institution for HFrEF over a period of 18 months. Laboratory tests were performed on the first 24 hours of admission. Patients were divided into two groups according to STC, using the value of 199 μg/dl as the cut-off. This value was determined from the ROC analysis to be the value with the highest sensitivity and specificity. Then we analysed relationship between STC at admission and all-cause mortality during follow-up between the two groups, after adjustment of the various variables described in the literature. Results Of 420 patients with HFrEF, 18.6% had STC ≤ 199 μg/dl (group 1) and 81.4% had STC > 199 μg/dl (group 2) with no difference in age and sex distribution (p = 0.873 ; p = 0.304). Patients with low STC were more likely to be diabetic (70.5% vs 46.5% ; p < 0.001), have dyslipidemia (52.6% vs 33%; p = 0.002), and history of chronic renal failure (6.4% vs 2.0% ; p = 0.045). There was no relation between STC and NYHA class (p = 0.776), hospital stay (p = 0.491) nor EF (p = 0.146). Biologically, lower STC was significantly associated with higher serum ferritin (292.77 vs 198.17 ; p < 0.001), TSAT (68.30 vs 22.21 ; p = 0.020) and C-reactive protein (CRP) (124.91 vs 39.98 ; p = < 0.001), lower plasma B-type natriuretic peptide (BNP) (5798.32 vs 6449.97 ; p = 0.002), with no difference in haemoglobin level (p = 0.272) and estimated glomerular filtration rate (eGFR) (p = 0.260). The prevalence of iron deficiency by the ESC criteria was lower in those with low STC; ferritin < 100 μg/l (15.4% vs 29.2% ; p = 0.015) or TSAT < 20% (33.3% vs 51,8% ; p = 0.004). There was no difference between the two groups in term of NYHA class and EF at three months (p = 0.87, p = 0.108). However, all-cause mortality during follow-up was significantly associated with low STC (37.2% vs 17.0% ; p <0.001). (Figure 1) In multivariable analysis, all-cause mortality was independently associated with STC ≤ 199 μg/dl (HR 1.71; 95% CI : 1.08 ; 2.7 ; p = 0.02). This is the same finding for the ischaemic origin of HFrEF (HR 2.1 ; p = 0.001), therapeutic inertia during follow-up (HR 5.53 ; p <0.001) and EF < 36% (HR 1.03 ; p = 0.047) (Figure 2). Conclusion More data are required before the routine use of STC as a biomarker of prognosis in HFrEF, but it may represent a reliable and cost-effective option to predict mortality.FIGURE 1FIGURE 2

Distinguishing Iron Deficiency Anemia From Beta-Thalassemia Trait: Comparative Analysis of CRUISE Index and Other Traditional Diagnostic Indices.

Introduction Iron deficiency anemia and beta-thalassemia trait are two common and important differentials of microcytic hypochromic anemia. Various discrimination indices using two or more common complete blood cell count (CBC) parameters have been used to distinguish between the two since1973. Recently, a new discriminant index, the CRUISE index, was proposed in the year 2019. The efficacy of various older indices along with the CRUISE index was evaluated for patients in our geographical area. Materials and method Ours was a laboratory-based, cross-sectional study where 100 patients, based on inclusion and exclusion criteria, with microcytic hypochromic anemia were evaluated for CBC parameters along with serum ferritin and hemoglobin-high performance liquid chromatography (Hb HPLC). A total of eight discrimination indices namely, Mentzer, Srivastava, Shine & Lal, Green & King, RDWI, England & Fraser, Kerman I and CRUISE index were used and evaluated for their diagnostic efficacy using different statistical parameters. ROC curves were obtained and a new cut-off value was proposed for our population. Data was analysed using Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and SPSS v29.0.2.0 (20) (IBM Corp., Armonk, NY, USA). Results Out of the total 100 cases, 39 were beta-thalassemia trait and 61 were iron deficiency anemia cases. The average age was 36.7 (±12.7 SD) years. Among the 73 females, 43 were diagnosed as iron deficiency anemia (IDA) and 30 as beta-thalassemia trait (BTT) cases. Among the 27 males, 18 were diagnosed as IDA and nine as BTT cases. The mean values were significantly lower in IDA patients for mean corpuscular volume (MCV) (p=.008), mean corpuscular haemoglobin (MCH) (p=.003), and mean corpuscular haemoglobin concentration (MCHC) (p=.003) and significantly higher for red cell distribution width (RDW) (p=.020). The mean ferritin levels in cases of IDA were 7.61 (±3.75) mcg/L and in BTT were 87.09 (±66.77 SD) mcg/L. The mean HbA2 levels in IDA cases were 2.75% (±0.41% SD) and BTT cases were 5.57% (±0.73% SD). CRUISEindex revealed the highest AUC (0.934), YI (76.21) and accuracy (90%) followed by the Mentzer index with a diagnostic accuracy of 81%. Shine & Lal index revealed the lowest AUC (0.710), YI (3.28) and accuracy (41%). Conclusion CRUISE index, which was recently proposed, was ranked 1st in terms of AUC, YI, and accuracy and was considered 2nd best in terms of sensitivity for differentially diagnosing the two conditions. Mentzer index, a commonly used index, also revealed a high diagnostic accuracy in our study for differentiating BTT from IDA. CRUISE index being a novel index, more research work needs to be carried out in various other geographical setups to evaluate the efficacy of this index.

Iron Metabolism in Pediatric Living related Liver Transplantation

Abstract Introduction Iron deficiency is a frequent cause of anemia in liver transplant recipients, especially children. Rejection and infection are incriminated causes for occurrence of anemia after liver transplantation (LR). Aim of the Work We aimed to assess iron homeostasis in children who have undergone living related LT (LRLT) and its correlation with occurrence of rejection and infection. Patients and Methods The study was conducted on 35 children who have undergone LRLT. The patient characteristics, frequency of infection and rejection episodes, laboratory investigations including complete blood picture (CBC) and Iron profile (total iron binding capacity (TIBC),serum iron and ferritin) during the patient follow up visits were reported. Results Males were 68.58% of the studied patients and females were 31.42%. Their ages ranged from 1.3-15 years at time of LT with mean (SD) of 7.18 (3.8)years. The mean (SD) duration since LT was 4.83 (4.2) years. The commonest indication to LT was highgamma-glutamyl transferase (GGT) cholestasis (34.7%) followed by biliary atresia (21.7 %). Thirteen percent of patients had low hemoglobin (Hb) of whom 4.3% had normocytic normochromic anemia and 8.7% had microcytic hypochromic anemia. Serum iron was normal in 79.6% of patients and low in 20.4%, and ferritin was normal in 58.7% of patients and low in 41.3% while TIBC was normal in 82.6% of patients and low in 17.4%. Only serum iron showed significant negative correlation with white blood cells (WBCs) (P < 0.05). The iron parameters levels were not different in patients with no rejection or only one attack of rejection and the patients with multiple rejection episodes (P > 0.05). Conclusion Anemia is a reported complication after pediatric LT. Further studies are needed to assess the long term effect of post-LT anemia on patient outcome after LT.

Retrospective Study Comparing Treatment Outcomes in Obstetric Patients With Iron Deficiency Anemia Treated With and Without Intravenous Ferric Carboxymaltose.

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions. In 2021, we initiated the administration of intravenous ferric carboxymaltose as an outpatient procedure. We compared the outcomes of patients between 2021 and 2023 after the initiation of outpatient administration of intravenous ferric carboxymaltose in 127 obstetric patients with iron deficiency anemia in the second and third trimesters. Methods In this study conducted in a large maternity unit in Singapore between 2021 to 2023, we compared the changes in maternal hematological parameters among obstetric patients with iron deficiency anemia presenting to the day care unit in the second or third trimester with a Hb level of <8 g/dl treated with a single dose of ferric carboxymaltose injection (Ferinject) against a control group who were referred for treatment but defaulted on and declined treatment. Results Ferric carboxymaltose significantly increased the Hb and MCV levels at delivery in obstetric patients with iron deficiency. The mean Hb at delivery was 10.8 g/dL in the case group compared to 8.8 g/dL in the control group. The percentage of patients with Hb ≥10.0 g/dL was 73.4% in the case group compared to 27.8% in the control group. The incidence of adverse side effects was low and mild (2/127; 1.6%). None of the patients received were hospitalized because of ferric carboxymaltose. Conclusion A single injection dose of ferric carboxymaltose as an outpatient antenatal procedure was easily administered and well tolerated. Obstetric patients with iron deficiency anemia who received intravenous ferric carboxymaltose had a significantly higher level of Hb than those who did not.

Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study

IntroductionIron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of...

Predicting response to iron supplementation in patients with active inflammatory bowel disease (PRIme): a randomised trial protocol

IntroductionIron deficiency anaemia (IDA) is the most common systemic manifestation of inflammatory bowel disease (IBD) that has detrimental effects on quality of life (QoL) and disease outcomes. Iron deficiency (ID),...

Serum Hepcidin Is an Early Predictor of Iron Depletion in Non-Anemic Blood Donors

Introduction Iron deficiency is one of the major concerns in repeated whole blood donors. Although taking iron supplementation, frequent whole blood donors sometimes suffer from iron depletion which contributes to adverse impact on donor's health and may reduce the donor blood pool. Laboratory parameters identifying iron depleted status could help early recognize donors at risk of iron deficiency. Hepcidin is a key iron regulator, which blocks ferroportin to inhibit iron absorption and iron release from hepatocytes. In iron depletion, hepcidin down regulates to encourage iron absorption. Previous data reported that serum hepcidin at less than 10 ng/mL was significantly associated with iron deficiency. According to the biological function and physiological response of hepcidin, we hypothesize that hepcidin could be an early predictor of iron deficiency status in non-anemic individuals. Methods This cross-sectional study was conducted at the Blood Bank Center at Chiang Mai University Hospital, Chiang Mai, Thailand in May 2023. After the informed consent was obtained, ninety-seven healthy repeated whole blood donors who had donated blood at least twice in the past year were recruited. The medical records were reviewed. Basic characteristics and laboratories including complete blood count, reticulocyte indices, iron parameters, and serum hepcidin were evaluated. Donors who had serum ferritin level less than 30 and 30-100 ng/mL were categorized as iron deficiency, and low ferritin group, respectively. Those who had ferritin more than 100 ng/mL were the control group. Logistic regression analysis was done to determine the value of serum hepcidin in predicting iron deficiency status in each group. Results The total of 97 repeated whole blood donors were recruited, 48 (49.5%) were women. Mean age was 34.6 ± 10.7 years. There were 8 donors in the iron deficiency group, 38 in the low ferritin group, and 51 donors in the control group. Mean hemoglobin levels were 13.4 ± 1.1, 13.8 ± 1.2, and 14.2 ± 1.2 g/dL in the iron deficiency, low ferritin group and control, respectively, (p = 0.796). White blood cell and platelet count were not different in these groups. Similarly, red cell indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and reticulocyte indices showed no difference among groups. Serum hepcidin had a significant difference between the three groups. Median levels of hepcidin were 2.61 (1.37, 3.4) and 12.35 (10.12, 15.57) ng/mL in the iron deficiency and the low ferritin group, respectively, compared to 26.01 (21.36, 39.08) ng/mL in the control group, (p &amp;lt; 0.001). Low serum hepcidin (less than 10 ng/mL) were found in 14 (36.8 %) donors who had ferritin levels less than 100 ng/mL, compared to only 1 (2.4%) donor in the control group, (p &amp;lt; 0.001). In addition, serum hepcidin showed a strong correlation with ferritin levels (r = 0.779). Logistic regression model showed that only female sex (OR: 2.87; 95% CI: 1.26, 6.56) and hepcidin (OR: 0.76; 95% CI: 0.66, 0.86) were significant predictors of repeated donors who were at risk of iron depletion and had the ferritin levels less than 100 ng/mL. Conclusions Frequent blood donors are at risk of iron depletion. Serum hepcidin was a significant predictor of iron depleted status in non-anemic donors. Serum hepcidin also showed a significant correlation with ferritin levels. The downregulation of serum hepcidin was detected prior to the changes of red blood cell indices and reticulocyte responses. Early recognition and identification of donors at risk of iron depletion and prompt iron restoration are the key to ensuring the donor safety and preserving adequate blood donor pool.

Tranexamic Acid Reduces Large Traumatic Bleeding and Mortality in Murine Iron Deficiency Anemia By Mechanisms Beyond Control of Fibrinolysis

Introduction Iron deficiency anemia (IDA) is common. Some clinical evidence suggests that IDA may aggravate traumatic hemorrhage and compromise outcomes. To study if IDA influences traumatic hemorrhage, coagulopathy, and mortality we developed a model of traumatic liver injury with and without tranexamic acid (TXA) in mice with dietary IDA and compared the results to control mice and mice after parenteral iron rescue. Materials and Methods Severe IDA was generated in C57BL/6J mice by starting an iron-deficient diet in 3-week-old mice for 8 weeks (+/- 1 mg intraperitoneal iron dextran 2 weeks before trauma). Control mice were fed a normal laboratory diet. IDA was confirmed by complete blood count, red cell indices, and liver iron. Mice (≈20 per group) were pre-treated with saline or TXA (10mg/kg) and subjected to liver laceration. Blood loss (weighing blood-soaked sponges from the abdomen), coagulopathy [APTT, Factor (F)II, FV, FVIII, FX, and fibrinogen), thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes] were analyzed at 60 minutes after trauma Cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-10, MCP-1, RANTES, and TNFα) were measured at baseline, 60 minutes and 6 hours post-trauma. Data were expressed as median and compared by Mann-Whitney test. Seven-day survival was analyzed using Kaplan-Meier curves. Results IDA manifested as hypochromic/microcytic anemia with significantly lower hematocrits compared to normal controls (32% vs 48%, p=&amp;lt;0.0001) and hepatic iron content (20.04 µg/g vs. 72.41 µg/g, p=&amp;lt;0.0001), respectively. Parenteral iron repletion corrected anemia and hepatic iron stores (“iron replete” mice). IDA mice experienced significantly higher blood loss compared to control mice (24.5 vs. 20.6 µL/g p=&amp;lt;0.0001), and TXA prophylaxis reduced blood loss significantly in both groups to ~15 µL/g. Blood loss in iron replete mice was 15.8 µL/g, and TXA did not reduce bleeding beyond the ~15 µL/g threshold. Bleeding led to a similar degree of acute traumatic coagulopathy (ATC) in all groups, characterized by APTT prolongation, TAT-complex formation, and depletion of FV, FVIII, and fibrinogen. FII and FX were not affected, consistent with the presence of ATC, rather than disseminated intravascular coagulation. TXA promoted the correction of ATC by near-normalization of TAT-complexes, FV, FVIII, and fibrinogen in all groups. In contrast, the extent of fibrinolysis differed in that PAP complex formation was significantly higher in IDA mice compared to control mice (44 vs 28 ng/mL, p=0.0004). TXA corrected PAP-complex formation and APTT only in control mice, without affecting these parameters in IDA mice. Seven-day survival was high in control and iron replete mice (~75%) without additional improvement by TXA. However, 7-day survival was lower in IDA mice (50%) and rescued by TXA (80%, p=0.04). A post-traumatic cytokine response was observed for the pro-inflammatory cytokines IL-1α, IL-6, MCP-1, RANTES, and TNFα. TXA mitigated this response substantially, but mostly in IDA mice, with little effect in control and iron replete mice. Conclusion IDA resulted in enhanced bleeding and mortality, which was rescued by parenteral iron correction or TXA prophylaxis. Interestingly, exaggerated fibrinolysis provoked by IDA could not be corrected by TXA, while TXA suppressed the pro-inflammatory cytokine response. This suggests that bleed and mortality rescue in IDA were less dependent on the anti-fibrinolytic effects of TXA, and more dependent on anti-inflammatory effects, which are poorly understood. These observations open new avenues to study pharmacodynamic effects of TXA beyond fibrinolysis inhibition, which may be particularly impactful for trauma rescue in the setting of anemia.

Iron status in early infancy is associated with trajectories of cognitive development up to pre-school age in rural Gambia.

Iron deficiency is among the leading risk factors for poor cognitive development. However, interventions targeting iron deficiency have had mixed results on cognitive outcomes. This may be due to previous interventions focusing on the correction of iron deficiency anaemia in late infancy and early childhood, at which point long lasting neural impacts may already be established. We hypothesise that the relationship between iron status and cognitive development will be observable in the first months of life and will not be recovered by 5 years of age. Using data from the Brain Imaging for Global Health (BRIGHT) Study in Gambia (n = 179), we conducted mixed effects modelling to assess the relationship between iron status at 5 months of age and trajectories of cognitive development from 5 months- 5 years using (i) a standardised measure of cognitive development (Mullen Scales of Early Learning) and (ii) an eye-tracking assessment of attention processing (visual disengagement time). All infants were iron sufficient at 1 month of age. At 5 and 12 months of age 30% and 55% of infants were iron deficient respectively. In fully adjusted analyses, infants in the lowest tercile of soluble transferrin receptor (sTfR) (best iron status) achieved MSEL Cognitive Scores on average 1.9 points higher than infants in the highest sTfR tercile (p = 0.009, effect size = 0.48). There was no evidence that this group difference was recovered by 5 years of age. Infants in the lowest sTfR tercile had visual disengagement time 57ms faster than the highest tercile (p = 0.001, effect size = 0.59). However, this difference diminished by early childhood (p = 0.024). Infants are at risk of iron deficiency in early infancy. A relationship between iron status and cognitive development is apparent from 5 months of age and remains observable at 5 years of age. One mechanism by which iron availability in early infancy impacts brain development may be through effects on early attentional processing, which is rapidly developing and has substantial nutritional requirements during this period. To support neurocognitive development, prevention of iron deficiency in pre- and early postnatal life may be more effective than correcting iron deficiency once already established.

Telephonic intervention to combat non-adherence to oral iron-folic acid supplementation in pregnancy: A randomized controlled trial

IntroductionIron deficiency anemia is a public health problem globally attributing to high incidences of maternal and infant mortality and morbidity. Iron and folic acid supplementation (IFAS) is essential and provided free of cost by the public health sectors, however, a systematic review shows that the national-level adherence to oral Iron-Folic Acid Supplementation (IFAS) is less than half in pregnant women, and the significant obstacles to non-adherence are fear of side effects and forgetfulness. This trial was designed to mitigate the side effects and tackle forgetfulness with telephonic intervention. The objectives were to investigate the effectiveness of the telephonic intervention on oral IFAS adherence and hemoglobin and the reasons for non-adherence to oral IFAS, to find out the proportion of anemia in the study population, and to assess the effectiveness of the intervention on maternal and neonatal outcomes. MethodsHospital-based open-label multi-centric parallel-group randomized controlled trial, used block randomization and allocated treatment in a 1:1 ratio recruited 286 anemic pregnant women between 14 and 24 weeks of gestation with hemoglobin level < 11 g/dl having smartphones at a secondary hospital and a tertiary hospital in Eastern India. The experimental group received telephonic intervention for one month via structured text reminders, WhatsApp audio messages, and phone calls. The standard course of treatment was given to the control group. Results286 women (n1 =143, n2 =143) were randomized, 36 had attrition leaving 250 for analysis (n1 =123, n2 =127), the experimental group experienced a 44.9 % and the control group 13.8 % increase in adherence (P < 0.001). The leading reasons for non-adherence were forgetfulness (24 %), nausea and vomiting (23.2 %), and constipation (18.8 %). Hemoglobin level increased by 0.8 g/dl (P < 0.001) in the experimental group and 0.2 g/dl (P < 0.807) in the control group. ConclusionIn addition to improving adherence to oral IFAS, telephonic intervention mitigates side effects and enhances hemoglobin in anemic pregnant women. The increase in adherence was threefold in the experimental group compared to a marginal rise in the control group. This study recommends the implementation of a telephonic intervention to promote adherence to oral IFAS among anemic pregnant women.

An Audit of Iron Deficiency in Hospitalised Heart Failure Patients: A Commonly Neglected Comorbidity.

Introduction Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF) and can significantly impact morbidity and mortality, regardless of the presence of anaemia. Aim This audit aimed to assess the current practice in diagnosing and assessing iron deficiency (ID) in hospitalised patients with heart failure and reduced ejection fraction (HFrEF). The primary goal was to determine the prevalence of ID in HF patients and the frequency of iron testing in those patients. Additionally, the secondary aims included evaluating the presence of anaemia, the length of hospital stay, and the adequacy of appropriate management for iron deficiency in this patient population. Methods A retrospective audit was conducted, reviewing data from patients admitted to St. Vincent University Hospital over a period of 4 months. Results Out of the 111 patients audited, only74% (82)had their iron status checked, and among those tested, 63% (52) met the criteria for iron deficiency according to the European Society of Cardiology (ESC).Additionally, 54% (28) of iron-deficient patients were also anaemic. Iron replacement was administered to 34 out of the 52 patients diagnosed with iron deficiency, accounting for 65% of the identified cases. The average duration of hospital stay for patients with iron deficiency was 13.8 days, while those without iron deficiency had a shorter mean length of stay of 11.2 days. However, it is important to note that the presence of co-morbidities and other confounding factors might have influenced these results. Conclusion Despite guideline recommendations, iron deficiency remains under-recognised and undertreated in clinicalpractice among heart failure patients. There is a crucial need for increased awareness, education, and practical guidance to improve the screening, diagnosis, and management of iron deficiency in hospitalised heart failure patients.

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

IntroductionIron deficiency (ID) is common and has been associated with an excess mortality risk in kidney transplant recipients (KTRs). In patients with chronic heart failure and ID, intravenous iron improves...

A new iron supplement: The chelate of pig skin collagen peptide and Fe2+ can treat iron-deficiency anemia by modulating intestinal flora.

Iron deficiency anemia (IDA) is one of the most common nutritional diseases encountered all over the world. Nowadays, oral iron supplementation is still the mainstay of IDA treatment. In this study, a new iron nutritional supplement named pig skin collagen peptides ferrous chelates (PSCP-Fe) was prepared, and its structure was characterized by the scanning electron microscopy, sykam amino acid analyzer and Fourier transform infrared spectroscopy (FTIR). The anti-IDA activity of PSCP-Fe was evaluated in low-Fe2+ diet-induced IDA in rats. 16S amplicon sequencing technology was then used to reveal the mechanism of PSCP-Fe against IDA. The results of amino acid analysis and FTIR showed that aspartic acid (Asp), arginine (Arg), histidine (His), glutamic acid (Glu), cystine (Cys), and lysine (Lys) residued in PSCP chelated readily with Fe2+ through their functional groups. PSCP-Fe treated reversed the hematology-related indexes, such as red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentrate (MCHC), serum ferritin (SF), serum hepcidin (HEPC) and serum transferrin receptor (TFR). And its regulatory action was better than that of FeSO4. Moreover, PSCP-Fe alleviated the hepatocyte apoptosis and necrosis, Fe2+ loss, and injury in IDA rats. In addition, PSCP-Fe could significantly retrace the disturbed profile of gut microbiota in IDA rats (p < 0.05) and significantly up-regulated the relative abundances of nine bacterial genus, including Lactobacillus, Alloprevotella, unclassified_of_Oscillospiraceae, and NK4A214_group (p < 0.05). It could also downgrade the relative abundances of Subdoligranulum and Coriobacteriaceae_UCG-002 (p < 0.05). The results of Spearman's correlation analysis and distance-based redundancy analysis (db-RDA) revealed that Subdoligranulum and Christensenellaceae_R-7_group may be potential microbial markers for effective PSCP-Fe action in the treatment of IDA. Overall, our results elucidate the interactions between gut bacteria and related cytokines and reveal the mechanisms underlying the anti-IDA effect of PSCP-Fe. They will thus provide a theoretical foundation for PSCP-Fe as a new iron nutritional supplement.

Ferumoxytol: an emerging therapeutic for iron deficiency anemia

ABSTRACT Introduction Iron deficiency anemia (IDA) is common worldwide, and various iron replacement therapies are available. Ferumoxytol is an injectable, high-dose iron formulation (510 mg) that can be administered over a short period (15 min) without test administration. The drug was approved by the Food and Drug Administration in 2009 for the treatment of IDA in patients with chronic kidney disease (CKD), and in 2018, the indication was expanded to include patients without CKD. Areas covered This paper reviews studies testing the efficacy and safety of ferumoxytol in treating IDA compared with other iron formulations. Expert opinion There is substantial evidence that ferumoxytol is effective for the treatment of IDA. The efficacy of ferumoxytol in improving anemia is comparable to that of iron sucrose and ferric carboxymaltose (FCM) and superior to that of oral iron or a placebo in replenishing iron stores. Treatment with ferumoxytol, although more expensive, is cost-effective for outpatients requiring parenteral administration because it requires fewer doses and shorter dosing times per dose. Ferumoxytol also causes less frequent hypophosphatemia than FCM. Currently, its use in children and pregnant women is under consideration, which may provide important information for the future applications of ferumoxytol in larger numbers of patients.

Iron Deficiency Is Commonly Observed in Female Multiple Sclerosis (MS) Patients with Relapsed/Refractory or Primary Progressive Disease Referred for Biological Therapies

Introduction Iron deficiency with or without anemia is common, symptomatic, and often underdiagnosed in women. Aging related iron deposition in the brain has been associated with multiple chronic neurological conditions, including multiple sclerosis (MS). MS is an autoimmune and inflammatory neurologic disease with a variable presentation and disease severity resulting from demyelination in the central nervous system. In MS, iron deficiency has been associated with more severe depressive symptoms and poorer quality of life. Overlapping symptoms shared by iron deficient and MS patients include fatigue, cognitive dysfunction and restless leg. Recognizing and treating iron deficiency is important in MS patients and may play a role in improving quality of life. Methods We conducted a retrospective study from January 2017 to December 2021 of MS patients referred to OHSU hematology clinic for therapy with monoclonal antibodies including ocrelizumab, rituximab, or natalizumab. Patient demographic, clinical, treatment and laboratory characteristics were reviewed. Iron deficiency was defined by presence of Ferritin < 50 ng/ml. Patients identified as iron deficient were reviewed for further gastro-intestinal and gynecologic work-up. Results A total of 307 patients with MS were identified. The median age was 49.3 (range 18-84), 104 were males (average age 50.7 at time of study) and 203 were female (average age 48.5 years at time of study). The majority of patients received ocrelizumab, with a minority receiving rituximab due to insurance coverage and rare patients receiving natalizumab. Ferritin levels were available in 114 patients. Of 20 male patients whose ferritin was checked, 4 were iron deficient. Of 94 female patients whose ferritin was checked, 56 (60%) were found to have past or current iron deficiency. In 15 of these 56 patients, GI findings were noted including: rectal cancer, adenomas, esophagitis, gastritis, large hiatal hernias, inflammatory bowel disease, H. pylori and bariatric surgery. The average age of women with GI findings was 48.7 years with an average ferritin of 19.2 ng/ml. In 12 patients, obstetric and gynecologic conditions were diagnosed. The average age of women with OB/GYN sources was 31.2 years with an average ferritin of 21 ng/ml (range). Three patients had combined GI and GYN causes, 4 were pending GI evaluations and 22 were not worked up for cause. Twenty-two women received treatment with intravenous iron products (iron dextran, iron sucrose, ferumoxytol, ferric carboxymaltose). In the 22 women treated with intravenous iron, 4 developed progressive MS symptoms leading to change in therapy. Conclusion Results show a high frequency of iron deficiency in women with multiple sclerosis. GI and GYN sources were the main causes for iron deficiency. Intravenous iron was used in a subset of patients with iron deficiency. Worsening MS related symptoms were observed in 4 patients treated with intravenous iron. All women with multiple sclerosis should be evaluated for iron deficiency and investigated for cause if iron deficiency is found. Future studies on the effects of adequately diagnosing and treating iron deficiency in patients with multiple sclerosis are warranted.

Retrospective Assessment of Total Cost of Care in Non-Dialysis Dependent Chronic Kidney Disease Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with chronic kidney disease. Iron deficiency occurs in 15% to 48% of non-dialysis dependent chronic kidney disease (ND-CKD) patients with anemia. Parenteral iron therapy is often required in ND-CKD patients with IDA who cannot tolerate or are nonresponsive to oral iron. Available IV iron treatments vary in the amount of iron dose per administration, the number of infusions required to achieve complete iron repletion and drug acquisition cost. The objective of this study was to compare healthcare costs between ferric carboxymaltose (FCM) and low dose IV iron (LDI) for the treatment of IDA in ND-CKD patients. Methods Medical and pharmacy claims from IQVIA PharMetrics® Plus data were analyzed. Adult patients who received first (index) dose of FCM or LDI (i.e., iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019 were included. Eligible patients were required to be continuously eligible 6 months before (baseline) and 12 months after index IV iron infusion and had medical claims associated with diagnosis of chronic kidney disease (ICD-10: N18.1 to N18.5) and IDA (ICD-10: D50.x) anytime during the 18-month study observation period. In addition, eligible FCM patients were required to receive a second dose of FCM within 21 days of index date. Patients who had claims associated with end stage renal disease (ICD-10: N18.5 and N18.6) or dialysis (HCPCS CPT code: 90935-90999) and patients who had received other IV iron products in the 6-month baseline period were excluded. Unadjusted mean number of IV iron infusions, outpatient visits and hospital admissions in the 6 months before and 12 months following index IV iron dose were summarized on a per-patient-per-month basis. Post-index monthly inpatient, outpatient, and total healthcare costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and the Charlson Comorbidity Index (CCI). Sensitivity analyses comparing FCM versus iron sucrose were performed. Results Data from 3,727 FCM patients [mean (SD) age= 67.9 (13.8) years, 61% females, CCI (SD)=1.9 (2.5)] and 5,068 LDI patients [mean (SD) age=64.8 (15.0) years, 60% females, CCI (SD)=1.6 (2.4)] were analyzed. Within the LDI cohort, 3,489 patients received index iron sucrose treatment [mean (SD) age=64.6 (15.1) years, 60% females, CCI (SD)=1.5(2.4)]. Mean (SD) number of IV iron infusions was 0.24 (0.26) for FCM, 0.43 (0.52) for LDI and 0.46 (0.52) for iron sucrose during the post-index period. During the post-index period, FCM has a smaller increase in the number of outpatient visits (mean change from baseline=0.13) than LDI (mean change from baseline=0.64) and iron sucrose (mean change from baseline=0.70). The number of hospital admissions in the post-index period were numerically lower for FCM (mean change from baseline=-0.05) but numerically higher for LDI (mean change from baseline=0.04) and iron sucrose (mean change from baseline=0.05). Mean total health care cost increased during the 12-month period after IV iron treatment compared to baseline in all treatment groups. After adjusting for pre-index cost and other covariates, FCM treatment was associated with significantly lower post-index inpatient costs [adjusted cost ratio (ACR)= 0.73, p<0.0001], ER costs (ACR=0.76, p<0.0001), outpatient costs (ACR=0.73, p<0.0001) and total costs (including IV iron) (ACR = 0.81, p<0.0001) than LDI. Similar results were observed in the comparisons between FCM and iron sucrose. Conclusion Higher drug acquisition cost of FCM compared to LDI was primarily offset by lower inpatient and outpatient costs during the 12 months after FCM treatment for IDA in ND-CKD patients than LDI, resulting in significantly lower overall total health care cost for FCM compared to LDI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Intravenous ferric derisomaltose in iron-deficient patients undergoing transcatheter aortic valve implantation due to severe aortic stenosis: study protocol of the randomised controlled IIISAS trial

IntroductionIron deficiency is a prevalent comorbidity in patients with severe aortic stenosis and may be associated with procedural and clinical outcomes after transcatheter aortic valve implantation (TAVI). In the Intravenous...