Treatment Of Iron Deficiency Anemia Research Articles

Ferric Carboxymaltose Versus Ferrous Glycine Sulfate For Treatment of Iron Deficiency Anemia and Their Effect On Vitamin B12 And Folic Acid: A Retrospective Study

Aim Anemia is a major public health problem, affecting about one-third of the world's population, and is most commonly caused by iron deficiency. Iron deficiency anemia requires oral or intravenous iron replacement therapy. The purpose of this study was to assess the change in several hematological parameters, vitamin B12, and folic acid from baseline to the first month of follow-up following therapy with oral ferrous glycine sulfate or intravenous ferric carboxymaltose. Methods: All patients who received oral ferrous glycine sulfate or intravenous ferric carboxymaltose for the treatment of iron deficiency anemia between January 1, 2016, and December 31, 2018, were included in the trial. Along with age and gender information, values of hemoglobin, ferritin, transferrin saturation, mean corpuscular volume, vitamin B12, and folic acid were derived from patients’ records at the beginning of treatment and first month follow-up. Results: Laboratory values obtained after treatment showed statistically significant improvement in both groups (intra group, p<0.001). When the percentage of change between groups was compared: Percentage-based increases in hemoglobin, mean corpuscular volume, transferrin saturation and ferritin values were significantly higher in the ferric carboxymaltose group (p<0.001). The percentage decrease in vitamin B12 and folic acid values was higher in the ferric carboxymaltose group (p=0.005 and p=0.01, respectively) when compared with oral ferrous glycine sulfate group. Conclusions: According to the findings of our study, iron deficiency anemia can be treated very successfully using ferric carboxymaltose; however, it should be remembered that concurrent supplementation of elements such vitamin B12 and folic acid is necessary for the appropriate progression of erythropoiesis.

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.

Markers of Oxidative Stress, Inflammation and Endothelial Function following High-Dose Intravenous Iron in Patients with Non-Dialysis-Dependent Chronic Kidney Disease-A Pooled Analysis.

Chronic kidney disease (CKD) represents a state of oxidative stress imbalance, which is potentially amplified by iron deficiency. Intravenous iron is considered safe and efficacious in the treatment of iron deficiency anemia, however, concerns remain regarding its potential pro-oxidant effect, leading to inflammatory and endothelial consequences. This pooled analysis of two pilot randomized controlled trials aimed to group and analyze the potential effect of high-dose intravenous iron (ferric derisomaltose, 1000 mg) on markers of oxidative stress (thiobarbituric acid reactive substance), inflammation (C-reactive protein, interleukins 6 and 10) and endothelial response (E-selectin, P-selectin) in patients with non-dialysis-dependent CKD and iron deficiency with/without anemia. Pulse wave velocity as a surrogate measure of arterial stiffness was measured. Thirty-six patients were included. No statistically significant trend was identified for any of the aforementioned markers. Stratification and comparison of data based on CKD stage did not yield statistically significant trajectories with the exception of the C-reactive protein in CKD stage 3b. These results suggest that high-dose intravenous iron does not impact measures of oxidative stress or inflammation; however, the results are not conclusive. Further research in a larger cohort is necessary to characterize the effect of intravenous iron on oxidative status and inflammation and its potential sequela in CKD.

The association between iron deficiency and outcomes: a secondary analysis of the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial.

In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre-operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30μg.l-1 ; functional iron deficiency as ferritin 30-100μg.l-1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9g.l-1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8g.l-1 , 95%CI -0.1 to 5.7; and with little change seen in those patients who were non-iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p=0.33 for interaction), transferrin saturation (p=0.13) or in combination (p=0.45), or for the number of blood transfusions (p=0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.

To evaluate the efficacy and safety of intravenous ferrous carboxymaltose compared with Iron sucrose in treating iron deficiency anemia in postpartum period

Background: Iron deficiency anemia continues to be a serious problem in developing countries resulting in spectrum of adverse events in pregnant women. The first choice for prophylaxis and treatment of mild IDA in pregnancy is oral iron therapy. However, in patients with moderate and severe anemia, oral therapy takes very long time and compliance could be a big issue in our country. Thus, pregnant women with moderate anemia should be better treated with parenteral iron therapy. Postpartum women were eligible for the study with hemoglobin level &lt;10 g/dl, while those with sickle cell anemia, aplastic anemia, megaloblastic anemia, etc., or having allergy to parental iron were considered not eligible for this study. The eligible women were randomly categorized to receive intravenous iron sucrose and intravenous ferrous carboxymaltose. Aims and Objectives: (1) To Compare ferrous carboxymaltose with iron sucrose in treating iron deficiency anemia in postpartum period (2) To assess the adverse effects and patient compliance. Materials and Methods: A comparative, prospective, and randomized distributed in 50 patients within the Department of Obstetrics and Gynecology, MGM Medical College and Hospital, Navi Mumbai. The subjects were randomized into two group, first group receiving iron sucrose, whereas second group receiving ferrous carboxymaltose. Results: Study, 25 women received iron sucrose and 25 women received ferrous carboxymaltose. There was significant higher increase in hemoglobin levels at 6 weeks in ferric carboxymaltose (FCM) group as compared iron sucrose group hemoglobin levels. There was significant higher increase in ferritin levels at 2 and 6 weeks in FCM group as compared iron sucrose group hemoglobin levels. There was significant higher increase in reticulocyte count at 6 week in FCM group as compared iron sucrose group reticulocyte count. Conclusion: Ferric carboxymaltose is safe and efficient in treatment of iron deficiency anemia in postpartum women as compared to iron sucrose with lesser adverse effect and better patient compliance.

Nano-formulations in treatment of iron deficiency anaemia: An overview

Iron deficiency anaemia (IDA) is a significant challenge to global health. The absorption and bioavailability depend on the delivery vehicle being used. Ferrous sulphate is a drug of choice for IDA but leads to frequent gastrointestinal tract side effects that force the patient to discontinue the treatment. Gastrointestinal side effects result from converting bivalent iron into trivalent iron accompanied by reactive oxygen species (ROS) formation. Due to lower absorption, oral preparations of trivalent iron are recommended in patients with intolerance to ferrous sulphate. Nanosized iron preparation can resolved these concerns. The particle size of iron salts has been observed to have a significant impact on iron absorption. The surface area of iron compounds is increased by reducing their particle size, which improves their solubility in gastric juice and boosts their absorption. Sucrosomial iron, ferric citrate complexes, and ferric maltol are some of the novel iron preparations that ensure high bioavailability and good tolerance in chronic kidney disease, congestive heart failure, and inflammatory bowel disease. However, the parenteral route of administration of iron is unacceptable to most patients. Moreover, it leads to high free iron levels in circulation, resulting in ROS generation. This article provides an informative summary of iron deficiency anaemia causes and treatment through nanoformulations and literature and in-depth patent analysis.

Protocol for a multicenter, double-blinded placebo-controlled randomized controlled trial comparing intravenous ferric derisomaltose to oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy: The IVIDA2 trial

Protocol for a multicenter, double-blinded placebo-controlled randomized controlled trial comparing intravenous ferric derisomaltose to oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy: The IVIDA2 trial

The effect of iron deficiency anaemia treatment on mean platelet volume.

To determine the relationship between mean platelet volume (MPV) and treatment response of iron deficiency anaemia (IDA) with normal platelet count. Study further aimed to determine changing of platelet parameters treatment response of IDA. IDA patients (n = 124) and the control group (CG) (n = 124) who fulfilled the inclusion criteria were compared for MPV and platelet parameters. Patients with IDA were divided into two groups as partial and complete response. The partial response to treatment group (PRG) was accepted as haemoglobin level between 10 and 12g/dL, mean corpuscular volume (MCV) below 80 fL, and ferritin below 15ng/ml (n = 60). Complete response to treatment group (CRG) was the patients whose haemoglobin was above 12g/dL, MCV is above 80 fL, and ferritin is above 15ng/ml (n = 64). The MPV levels of CG (8.81 ± 0.99), PRG (8.80 ± 1.09), and CRG (8.96 ± 0.96) were similar at the beginning of the study. In addition, MPV levels of PRG (8.84 ± 1.08) and CRG (8.96 ± 1.11) with IDA therapy were similar at the end of the study (p > 0.05). When IDA was treated, there was a decrease in plateletcrit, platelet distribution width (PDW), and platelet count from platelet parameters. There was a correlation between MPV level and platelet count in both PRG and CRG (r = - 0.506; p < 0.001), (r = - 0.499; p < 0.001). There is no change in MPV levels before and after treatment when normal platelet count IDA is treated, but there is a decrease in platelet count and an increase in PDW.

Patient Reported Outcomes after Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study

Objective: Fatigue is a common symptom reported by iron deficiency anemia (IDA) patients. Iron deficiency has also been shown to reduce physical function independent of anemia. Parenteral iron therapy is indicated for the treatment of iron deficiency anemia (IDA) in patients who are intolerant or nonresponsive to oral iron. This study assessed fatigue symptoms and patient-reported functioning in IDA patients for up to 6 months after treatment with ferric carboxymaltose (FCM). Methods: This prospective, single arm, longitudinal observational study included adult patients diagnosed with IDA who were prescribed FCM under routine clinical care across 7 clinical practice sites in US. Eligible patients had baseline serum hemoglobin of >7 g/dL and <13 for males or <12 for females, no potential contraindications to FCM, and no parenteral iron therapy within 3 months before study enrollment. Patients completed patient-reported outcome (PRO) questionnaires prior to receiving FCM treatment, and at 3 months and 6 months after the first course of FCM. PROs included the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale, the Patient Reported Outcomes Measurement and Information System (PROMIS) Physical Function v2.0 Short Form, and the PROMIS Global Health v1.2 Short Form (physical and mental health). A higher FACIT-Fatigue or a lower PROMIS Physical Function, PROMIS Global Physical Health or Mental Health score indicate more health problems. For each measure, a mean change from baseline of ≥5 points was considered clinically meaningful. Associations between baseline serum hemoglobin and each PRO score were assessed using Spearman's rank correlation coefficient. Results: 152 patients with median IDA history of 2.0 years were included in the intent-to-treat population (mean age=47.4 ± 16.0 years, 82.2% females, 17.1% with inflammatory bowel disease, 13.8% with abnormal uterine bleeding, 9.2% with cancer, mean baseline serum Hgb =10.19±1.35 g/dL). About one-third of patients (34.9%) had oral iron treatment and 2.6% had a blood transfusion within 3 months prior to FCM treatment. A small proportion of patients (6.6%) had parenteral iron treatment in the 12 months before study enrollment. Most patients (83.6%) were prescribed 2 doses of FCM (total dose of 1500mg) at baseline. Within 6 months after the first course of FCM, no patient received treatment with erythropoietin stimulating agents, 1 patient received a blood transfusion, and 14 (9.7%) patients required additional IV iron treatment after the initial course of FCM treatment prescribed at baseline. Median time from baseline to additional IV treatment was 86.5 days. Fatigue symptoms were improved after FCM treatment, as indicated by significantly lower mean FACIT-Fatigue scores at 3 months (50.19 ± 9.51) and at 6 months (52.42 ± 9.31) compared to baseline (61.01 ± 8.96), with p<0.0001 each. A majority of patients had a reduction of at least 5 points in FACIT-Fatigue score from baseline to 3 months (72.7%) and 6 months (67.3%), respectively. Physical function also improved, as indicated by significantly higher mean PROMIS Physical Function score at 3 months (46.08 ± 8.52) and 6 months (45.15±8.85) compared to baseline (41.31±8.63), with p<0.0001 each. Improvements in PROMIS Global Physical Health (p<0.0001) and the PROMIS Global Mental Health score (p=0.0027) were also observed at 3 months and 6 months compared to baseline. Correlations between baseline serum hemogloblin levels and PRO scores were borderline to highly significant, with correlation coefficients of 0.151 (p=0.0647) with PROMIS Global Mental Health, 0.276 (p=0.0006) with Global Physical Health, 0.286 (p=0.0004) with PROMIS Physician Function and -0.294 (p=0.0002) with FACIT-Fatigue. Conclusions: IDA patients treated with FCM reported significant reduction in fatigue symptoms and improvements in physical function, physical health and mental health at 3 months after treatment. These benefits were sustained at 6 months after treatment, with only a small proportion of patients requiring re-treatment with additional IV iron beyond the initial course of FCM treatment. Significant correlations between serum Hgb and PRO scores observed in this study suggest that data collected directly from patients in a real-world setting can provide a valuable supplement to traditional clinical outcomes for evaluating treatment effectiveness. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ferric Carboxymaltose for Long-Term Correction of Iron Deficiency Anemia in the Emergency Department

Background: Despite the implementation of the Choosing Wisely Campaign of the AABB (formerly the American Association of Blood Banks), red blood cell (RBC) transfusions continue to be a common choice of treatment for iron deficiency anemia (IDA) in hemodynamically stable patients presenting to the emergency department (ED). This occurs despite the considerable risk and high cost of RBC transfusions and the availability of alternative treatments with robust safety profiles such as intravenous (IV) iron. An understanding of the patient clinical factors that affect the decision to transfuse is essential to narrowing the gap between clinical guidelines and current clinical practice, and to ensuring appropriate RBC usage. Aims and methods: To assess the clinical management of severely anemic, hemodynamically stable patients presenting to the ED, we performed an observational, retrospective study at a tertiary care hospital in Milan, Italy, over a five-year period from 2017 through 2021. Only patients with severe anemia (i.e., hemoglobin < 8 g/dL) were included. Patients with conditions for which transfusion is the first-line treatment, including hemoglobinopathies and active onco-hematological disorders, were excluded. Results: 967 patients were included in the study. The population was 63% female with a median age of 77 years (IQR, 61-85). Hematological parameters (Table 1) characterized the study population as microcytic, with high red cell distribution width (RDW) and, when available, low ferritin values, indicative of a significant role of iron deficiency anemia within the population. 72% of patients (n=700) received a transfusion in the ED. 20% (n=189) received both transfusion and IV iron, 11% (n=108) IV iron only, and 16% (n=159) received neither transfusion nor intravenous iron. Half of the subjects presented to the ED with symptoms, largely with asthenia and exertional dyspnea, while severe symptoms (palpitations, syncope, chest pain) were present in less than 4% of patients. Gastrointestinal bleeding (33%, n=319) was the most common known cause of anemia, followed by gynecological bleeding (6%, n=56). For data analysis, patients were divided into two treatment groups (transfused (T) vs. non-transfused (NT)) and two outcome groups (discharged (D) vs. admitted (A)). Patients with documented heavy gynecological bleeding were more represented in the transfused group and the discharged group (T:3.7% vs NT:11.2%; D:0.8% vs A:10.3%; p<.001). Similarly, patients with malabsorptive diagnoses (e.g. celiac disease, inflammatory bowel disease, bariatric surgery) were more prevalent among those discharged (A:1% vs D:3.1% p=.027). Patients with cardiovascular disease were more represented among those transfused (T:42.3% vs NT:24.3%, p<.001) and among those admitted (A:42.4% vs D:32.7%, p=.002). Diabetic patients were likewise more prevalent among those transfused (T:17.8% vs NT:11.2%, p=.012) and those admitted (A:18.8% vs 13.3%, p=.020). Patients on antithrombotic therapies were more represented in the transfused (T:49.7% vs NT:27.7%, p<.001) and admitted (A:48% vs D:39.5%, p=.008) groups. Discharged patients who received IV iron in the ED saw significantly higher increases in hemoglobin levels at an initial (mean 18 days post-discharge) and second (mean 41 days) follow-up (Table 2). Transfused patients spent a mean 12.8 hours longer in the ED than those who were not transfused, demonstrative of a significantly higher utilization of ED resources in the administration of red blood cells. Conclusions: Our study demonstrated a high usage of red blood cell transfusions to treat anemia in the ED. Overall, transfused patients were older, with a higher prevalence of cardiovascular disease and diabetes and anticoagulant or antiaggregant therapy. It seems probable that these characteristics could have influenced the physician in the decision to transfuse. IV iron preparations were demonstrated to not only be effective in managing severe iron deficiency anemia in the ED but also more efficacious in the long-term correction of anemia. Our study overall demonstrated a continued knowledge-to-practice gap in the management of severe anemia in the emergency department. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

To observe the rise in haemoglobin concentration levels by parenteral iron infusion of iron isomaltoside 1000 (Fur-IV) in gynaecological patients suffering from iron deficiency anaemia

Iron Isomaltoside 1000 (Fur-IV) is a combination of iron and isomaltoside 1000(carbohydrate) which are strongly bound allowing slow and controlled release thereby reducing risk of free iron toxicity and offers high dose flexibility and administration and convenience. It is shown to be effective in treating iron deficiency anaemia across multiple therapeutic groups and compared to IV iron sucrose, Ferric carboxymaltose, and oral iron. It is effective and well tolerated in treatment of anaemia across different therapeutic areas with favourable safety profile. To observe the rise in level of haemoglobin concentration in gynaecological patients suffering from iron deficiency anaemia via single infusion of iron isomaltoside 1000 (Fur-IV).A prospective, observational study.Total 50 women who were attending OPD or an indoor patient of obstetrics and gynaecology department who were diagnosed with iron deficiency anaemia and confirming to inclusion criteria were enrolled and observed in this study. Written and informed consent were taken from all patients and data were recorded in the case record form. Detailed medical history and iron demand of the patient were taken and calculated before administration of IV Iron Isomaltoside 1000 by our department of OBGY. Data of the patients who were enrolled in the study were recorded including their haemogram report before administration and repeat haemogram at 1 and 2 week after administration. We did the study from May, 2021 to June, 2022 in OBGY department of Scientific Research Institute, Surendranagar, Gujarat, India. There were no serious adverse events (AE) reported. Only 6 patients reported adverse events [mild nausea, vomiting n=2; fetal bradycardia, n=2; pruritus, n=1; giddiness, n=1. Mean change in Hb is evaluated in 50 patients, increased significantly from 8.63 ± 1.18 gm/dl at baseline to 10.74 ± 1.08 gm/dl (difference of 2.11 ± 0.77 gm/dl; p &amp;#60; 0.001) at 2 weeks post-treatment. Safety and efficacy of Fur-IV was rated by physicians as ‘excellent and good’ in 98% patients.Iron isomaltoside 1000 (Fur-IV) has demonstrated robust efficacy in patients suffering from Iron deficiency anaemia due to pregnancy. The wide dosing range of Iron isomaltoside allows iron correction in a single visit with minimal risk of anaphylaxis and is thus cost‑effective for health‑care system.

Preliminary Results of a Phase-2 Clinical Trial of the ALK-2 Inhibitor Ker-047 for Treatment of Iron Refractory Iron Deficiency Anemia

Background: Iron refractory iron deficiency anemia (IRIDA) is a rare autosomal recessive disorder, caused by a genetic defect in TMPRSS6. This results in increased signaling through the bone morphogenic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway, leading to disproportionally high levels of hepcidin relative to body iron status. Hepcidin reduces iron transport to the plasma by degrading the cellular iron exporter ferroportin, resulting in systemic iron deficiency and microcytic anemia. Symptomatic interventions such as intravenous iron administration results in iron sequestration in the reticular endothelial system (RES) and generally only a partial response of hemoglobin concentrations. Further, the potential long-term adverse effects of chronic intravenous iron therapy and associated elevated RES-iron levels are unknown in these patients. Blood transfusion can be administered in cases of severe symptomatic anemia but is generally avoided due to transfusion-related risks. Currently, there is an unmet need for more effective, safe, convenient, and direct-acting treatments for IRIDA. Given the central role of aberrant BMP/SMAD signaling in hepcidin production, selective inhibition of the BMP receptor ALK2 to reduce hepcidin represents a rational approach to target a precipitating factor of IRIDA. Preclinical studies in the TMPRSS6 siRNA knockdown mouse model of IRIDA demonstrated that treatment with a selective ALK2 inhibitor reduced hepcidin, increased serum iron, and ameliorated anemia. KER-047 is a novel, oral, investigational, small-molecule kinase inhibitor with potent and selective inhibitory activity against the ALK2 receptor. In a Phase 1 clinical trial, single-ascending and multiple-ascending doses of KER-047 administered to healthy participants resulted in robust decreases from baseline in hepcidin levels, increases in serum iron and transferrin saturation (TSAT), decreases in serum ferritin, and increases in reticulocyte hemoglobin content (Ret-He). Based on these observations, KER-047 was advanced to Phase 2 clinical trials. Aims: The primary objective of this ongoing Phase 2 clinical trial is to evaluate the safety and tolerability of ascending doses of KER-047 in participants with IRIDA. Secondary objectives include evaluation of pharmacokinetic (PK) and pharmacodynamic (PD) parameters. Methods: This is a 2-part open label, dose escalation and dose expansion trial. Part 1 (dose escalation) consists of up to 4 ascending dose cohorts starting with 25 mg q.d. Part 2 will be the dose expansion phase with safety as the primary focus. Patients diagnosed with IRIDA may enroll in all cohorts in Parts 1 and 2. Key inclusion criteria include diagnosis of IRIDA based on a homozygous or compound heterozygous TMPRSS6 genotype, a TSAT <15%, a ferritin level 50-700 µg/L and hemoglobin <13.8 g/dL (males) or <12.7g/dL (females) and signed informed consent. Patients are excluded if they have received IV iron treatment within 28 days prior to trial entry. Participants will be treated once daily with KER-047 for a 2-week period, followed by a 2-week washout period. Data are analyzed by using descriptive statistics. Results: At the time of this abstract submission, one participant had enrolled in the first dose-expansion cohort (KER-047 25mg q.d.). This participant reported intermittent dizziness, however no serious adverse events were observed during treatment. Hemoglobin concentration and mean corpuscular volume remained stable. Ret-He increased by day 5 of treatment. Ferritin levels decreased during treatment and returned to baseline levels after the 2-week treatment period. TSAT/hepcidin ratio, which is characteristically below reference intervals in IRIDA patients, was slightly increased but returned to baseline levels after 2-weeks treatment. Conclusion: Data are preliminary and limited to a single participant thus far in whom KER-047 25mg q.d. was well tolerated. Changes in red cell and iron parameters at this low dose support development of KER-047 as an agent to potentially address an underlying cause of IRIDA. At the time of this abstract submission, two additional patients are scheduled for screening to complete the first dose cohort. We anticipate data from the total of three patients in time for the presentation to further characterize safety of KER-047 and substantiate effects on iron metabolism. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Individual and community level determinants of iron intake among children 6–59 months old in Ethiopia: multilevel logistic regression analysis

BackgroundIron deficiency is one of the most important factors of anemia which is caused by poor iron intake. In addition, children need more iron because of their rapid growth. On the other side, daily intake of iron is also recommended as a standard approach for the treatment and prevention of iron deficiency anemia. In Ethiopia, although more than half of children 6–59 months of age were affected by anemia, the magnitude and factors associated with iron intake among them are understudied. Therefore this study aimed to assess the magnitude and community and individual level determinants of iron intake among 6–59 months children in Ethiopia.MethodsDemographic and Health Survey datasets (EDHS) were used for this study. The data were weighted using sampling weight to get valid statistical estimates. The total weighted samples of 9,218 children aged 6–59 months were included. A multilevel binary logistic regression model was fitted to identify factors associated with iron intake among 6–59 months of children in Ethiopia. In the final model adjusted odds ratio with a 95% confidence interval and p-value < 0.05 was taken to declare statistical significance.ResultsThe magnitude of iron intake among children 6–59 months in Ethiopia was 9.24% (95% CI: 8.31%, 10.15%). Individual level variables such as having at least one antenatal care visit (ANC) [AOR = 1.27; 95%CI; 1.01, 1.61], having health institution delivery [AOR = 1.46; 95%CI;1.04, 2.04], age of children ≥ 24 months [AOR = 1.82; 95%CI; 1.29, 2.57], being female child [AOR = 0.81; 95%CI; 0.67, 0.99], being greater than three birth order [AOR = 0.73, 95%CI: 0.55, 0.98], whereas community level variables such as living in large central regions [AOR = 3.68; 95%CI; 1.47, 9.21], and living in community with high women education [AOR = 1.96; 95%CI; 1.28, 2.98] have an association with iron supplements among children 6–59 months years old in Ethiopia.Conclusion and recommendationsThe magnitude of iron intake among children 6–59 months old in Ethiopia is relatively low. Individual level factors such as; ANC visit, institution delivery, age of children, sex of the child, and birth order as well as; community level variables such as regions, and community women's education have a significant association with iron intake among children 6–59 months in Ethiopia. Prior attention should be given for under two years old children, children greater than three birth orders, and children living in small peripheral regions. Moreover, policymakers and other stakeholders had better plan and implement programs that empower women, enhance ANC visits, and health institution delivery to have a sustainable increment in iron intake for children in Ethiopia.

The Empower Study - Design of a Randomized Clinical Trial to Assess the Efficacy and Safety of a Plasma-Derived Von Willebrand Factor / Factor VIII Concentrate for Heavy Menstrual Bleeding in Women with Von Willebrand Disease

Background: Although von Willebrand disease (VWD) is inherited by men and women equally, women are more likely to experience bleeding symptoms due to the challenges of menstruation and childbirth. Heavy menstrual bleeding (HMB) is the most common symptom observed in women and girls with VWD, and increases risk of iron deficiency anemia, blood transfusion, hospitalization and decreased health-related quality of life. While replacement therapy with von Willebrand factor (VWF) is recommended for prophylaxis in patients with VWD with severe and frequent bleeding, recommendations on its use for prophylaxis of HMB are limited due the lack of clinical trial data. Aims: The EMPOWER pilot trial will determine the feasibility of the trial design, as well as explore assay sensitivity to inform the determination of the primary outcome for the definitive randomized trial which will evaluate the effect of prophylaxis with plasma-derived VWF/FVIII (1:1; pdVWF:FVIII) concentrate compared with placebo on HMB in women with VWD. Methods: EMPOWER is a pilot, randomized, placebo-controlled, crossover, double-blind (patient and outcome assessor blinded), 2-year trial in female outpatients with VWD and HMB. We will evaluate the effect of 2-3 doses of prophylaxis with 40-60 IU VWF:RCo/kg pdVWF/FVIII concentrate when provided on the 2 heaviest days within the first 4 days of menstruation compared with placebo (normal saline). For the first treatment period, participants will be randomized to receive either pdVWF/FVIII concentrate or placebo for 4 cycles, crossing over to the comparator treatment during the second treatment period (see Figure 1). Non-pregnant female patients, ≥18 years of age with a diagnosis of inherited VWD (any type) with HMB defined as a modified pictorial blood assessment chart (mPBAC) score >100, on stable treatment for HMB and iron-deficiency anemia will be eligible. Patients with diagnosis of another bleeding disorder or the presence of >2 risk factors for venous thromboembolism will be excluded. The pilot trial viability outcomes include blinding index scores and participant drop-out rates. Feasibility outcomes include data completeness and rate of enrolment. The proposed primary clinical efficacy outcome is the mPBAC score and the key secondary efficacy outcome is the need for rescue therapy (i.e. >2 days of oral tranexamic acid use, additional treatment with pdVWF:FVIII concentrate, additional hormonal therapy for HMB, urgent/emergent gynecological surgery for HMB, treatment with intravenous iron, red blood cell transfusion, or hospital admission for HMB). Other secondary outcomes include major bleeding, clinically relevant non-major bleeding, red blood cell transfusion, fatigue and quality of life scores. Given the uncertainty in this area of research and the relative comparable clinical importance of proposed clinical efficacy outcomes, we will evaluate assay sensitivity to determine the outcome that has the greatest chance of detecting a difference between treatment periods. Assay sensitivity is defined as the ability of a scale to distinguish an effective from a less effective intervention or placebo. Assay sensitivity along with the proportion of missing data per clinical efficacy outcome and sample size considerations will influence the choice of primary outcome for the definitive trial. Safety will be evaluated by monitoring for hypersensitivity reactions, thromboembolic events and VWF inhibitors. The pilot trial will recruit 20 participants from Hemophilia Treatment Centres in Canada over 2 years. Results: The pilot trial is aiming to launch by the fall 2022. If the pilot trial is deemed feasible and viable, we will subsequently conduct a definitive international randomized controlled trial. Conclusion: Data from the EMPOWER trial will fill an important knowledge gap to facilitate evidence-based management of HMB in women with VWD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Differential Recovery of Macrophage Iron Deficiency By Oral Iron Formulations Determines Cell Inflammatory Response in Conditions of Iron Deficiency Anemia

Introduction: Sucrosomial iron (SI) is an innovative oral iron formulation which is absorbed intact through para and trans-cellular intestinal routes as well as via M-cells. Once in the circulation SI is internalized intact by reticulo-endothelial macrophages, which likely play a major role in iron recycling from the sucrosome shell and release into the bloodstream where iron joins the transferrin (Tf)-bound iron pool. By contrast, the common oral iron salt iron sulfate (FeSO4) is absorbed via the canonical inorganic iron pathway involving DMT1 and FPN and directly joins the Tf-bound iron pool. FeSO4 administration generates higher levels of free non-transferrin-bound iron (NTBI) to which macrophages can be exposed, leading to cell iron accumulation. Thus iron provided both as SI or FeSO4 can target macrophages. Recently, macrophage iron overload has been implicated in sterile inflammation through ROS-dependent cell pro-inflammatory activation. Here we investigated and compared how SI and FeSO4 shape the polarization status of macrophages and affect inflammation in conditions of iron deficiency anemia. Methods: To this aim, iron-deficient wild-type mice administered a low iron diet (<10ppm) were repeatedly treated with SI or FeSO4 every day for 2 weeks to correct their anemia, and hepatic and splenic macrophages were analyzed in term of cell iron status and inflammatory response. Results: Iron-deficient mice treated with SI showed an efficient but slightly slower recovery of anemia as monitored by blood parameters (e.g. Hb, RBC, HCT) compared to FeSO4-treated animals. The gradual anemia recovery by SI likely reflects the additional macrophage-dependent processing needed to recycle iron from the intact SI shell, which is not required following FeSO4 absorption. Indeed, Tf saturation and NTBI were more elevated in FeSO4-treated than SI-treated mice. Consistent with these observations, FeSO4 corrected intracellular iron deficiency in macrophages more rapidly than SI, as indicated by a more pronounced TfR1 suppression and bigger labile iron pool. This triggered more elevated ROS levels and increased apoptosis in macrophages from FeSO4-treated compared to SI-treated mice. Importantly, the faster cell iron deficiency recovery was associated with TNFα, IL1β and IL-6 release in macrophages from FeSO4-treated mice, which remained almost negligible in cells from SI-treated animals. In vivo findings are fully recapitulated in vitro in iron-deficient bone marrow-derived macrophages (BMDM) exposed to SI or FeSO4. FeSO4 corrected macrophage iron status faster than SI, as suggested by a quick rise in labile iron pool and suppression of TfR1 after 2h of treatment. By contrast, SI showed a slower and progressive ability to improve cell iron deficiency, modulating LIP and TfR1 after 5h of treatment, in agreement with a longer recycling process of iron from the SI shell. While FeSO4 exposure caused a massive increase in ROS levels and a significant elevation of inflammatory cytokines, SI minimally affected ROS and inflammatory cytokine production in BMDMs. Conclusions: Our data indicate that the gradual cell iron deficiency correction by SI exerts a protective effect in macrophages against iron-mediated inflammatory activation by limiting ROS formation, suggesting that the kinetic of cell iron accumulation determines macrophage inflammatory response. Overall, these studies show that SI is a superior oral iron formulation than iron salts in terms of reduced pro-oxidant and inflammatory action, with relevance for iron deficiency anemia treatment in individuals with pre-existing inflammatory conditions, including chronic kidney disease, anemia of cancer, inflammatory bowel disease, ulcerative colitis, post-operative anemia, celiac disease and obesity.

Comparison of the use of intravenous iron sucrose with intravenous ferric Carboxymaltose for treatment of iron deficiency anaemia in pregnant patients

BACKGROUND &amp; OBJECTIVE: Iron deficiency results in major disabilities and death all over the world, about two billion people are suffering from anaemia at the moment. To compare intravenous iron sucrose with intravenous ferric carboxymaltose in terms of mean change in hemoglobin level and mean corpuscular volume (MCV) for treatment of iron deficiency anaemia in pregnant patients.&#x0D; METHODOLOGY: Prospective comparative study was conducted at the department of Obstetrics/ Gynecology of POF Hospital Wah Cantt and HIT Hospital Taxila Cantt. The study duration was 2 years, from January 2017-December 2018. A total of 80 patients were included in the study. Patients were randomly divided into two groups; in Group-A; 40 patients were given intravenous iron sucrose, and in Group B, 40 patients were given intravenous ferric carboxymaltose. Patients were observed for hemoglobin level and mean corpuscular volume (MCV). Data analysis was done with SPSS version 24. An Independent t-test was applied, and results with p-value ≤0.05 were found significant.&#x0D; RESULTS: Post-treatment hemoglobin means level in the iron sucrose group was 9.90±0.4SD, and in the intravenous ferric carboxymaltose group, post-treatment hemoglobin was 10.71±0.9SD (p≤0.001). In the iron sucrose group, the post-treatment mean corpuscular volume mean level was 81.94±6.0SD and in the intravenous ferric carboxymaltose group mean post-treatment mean corpuscular volume was 88.08±7.1SD (p≤0.001)&#x0D; CONCLUSION: Treatment with intravenous iron caboxymaltose is superior to intravenous iron sucrose with respect to hematological response, which seems to be safe, as very few severe side effects were observed.

Application progress of high-dose intravenous iron in the treatment of iron deficiency anemia

Application progress of high-dose intravenous iron in the treatment of iron deficiency anemia

Effect of inulin, galacto oligosaccharides and iron fortification on iron deficiency anemia among women of reproductive age; a randomized controlled trial

Iron supplementation and fortification are the well-known approaches to treat iron deficiency anemia (IDA) in women of reproductive age. The objective of the current randomized controlled trial (RCT) was to evaluate the cumulative effects of prebiotics and iron fortification among women of reproductive age. For this purpose, a total of 75 iron deficient women of childbearing age were recruited and randomly divided into 5 groups (4 treatment groups and 1 control group). Four different types of fortified wheat flour were prepared using two iron fortificants (NaFeEDTA and FeSO4) and two prebiotics [inulin and galacto oligosaccharides (GOS)], while control group was treated with iron fortified flour without any prebiotics. Blood samples were collected from overnight fasted women on monthly basis up to 90 days. Hematological indices such as Hemoglobin (Hb), Hematocrit, Red Blood Cell (RBC) Count and Mean Corpuscular Volume (MCV), as well as iron biomarkers including serum iron, ferritin, transferrin, and Total Iron Binding Capacity (TIBC) were evaluated for analyses. The results showed a considerable positive improvement in all iron biomarkers as well as hematological indices among the treatment groups (P-value < 0.05), as compared to the control group. A maximum Hb (11.86 ± 0.24 mg/dL) and hematocrit value (35.06 ± 1.32%), was reported in group G3 which was treated with fortified wheat flour at a dose of 963 mg/kg GOS + 15 ppm FeSO4. On the other hand, highest mean values for RBC Count (4.73 ± 0.41 mil/mm3), MCV (81.41 ± 3.21 fL), serum iron (75.62 ± 2.79 μg/dL), serum transferrin (16.82 ± 0.30 mg/dL), and TIBC (403.68 ± 7.27 μg/dL) were observed in G4 group receiving the fortified wheat flour at a dose of 963 mg/kg GOS + 30 ppm FeSO4 level. The study concluded that prebiotic fortification along with iron salts helps to enhance iron absorption among iron deficiency anemic women of reproductive age.

Iron deficiency in women: ways to reduce prevalence

Iron deficiency states (IDSs) are common disorders at the nexus of various fields. The etiology and pathogenesis of IDSs have been well studied in recent decades, but their prevalence is still high. The highest incidence of IDSs is reported in women of reproductive age. The timely correction of iron deficiency improves women's quality of life and reduces pregnancy complications and infant morbidity. To achieve and maintain the improvement, caution in risk groups, early diagnosis, physiology-based therapy, and follow-up are necessary. Iron sulfate agents are well known as an effective way to treat iron deficiency anemia. However, the high rate of previously reported side effects posed significant challenges to the complete course of therapy. The development of a new molecule with prolonged iron release minimizes the complications of therapy, providing new prospects for iron deficiency treatment. The combination of folic acid to iron sulfate in one tablet simplifies prevention regimens and therapy for pregnant women and those planning to become pregnant and reduces the time to improve.

Protocol for a multicenter, double-blinded placebo-controlled randomized controlled trial comparing intravenous ferric derisomaltose to oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy: The IVIDA2 trial

BackgroundIron deficiency anemia (IDA) is common during pregnancy and associated with adverse maternal and neonatal outcomes. Treatment with iron supplementation is recommended during pregnancy, but the optimal delivery route is unclear. Oral iron risks has high risk of gastrointestinal side effects and low absorption. Intravenous iron is infused directly but is expensive. The American College of Obstetricians and Gynecologists currently recommends oral iron to treat IDA in pregnancy with intravenous iron reserved as second-line therapy, if needed. This approach is associated with persistent anemia, increasing the risk of peripartum blood transfusion. We aim to provide data on optimal route of iron repletion for IDA in pregnancy. MethodsIn IVIDA2, a double-blind, placebo controlled, multicenter randomized trial in the United States, 746 pregnant people with moderate-to-severe IDA (hemoglobin <10 g/dL and ferritin <30 ng/mL) at 24–28 weeks' gestation will be randomized 1:1 to either a single 1000 mg dose of intravenous ferric derisomaltose and oral placebo (1–3 times daily) or a single placebo infusion with 1–3 times daily 325 mg ferrous sulfate (65 mg elemental iron) tablet. The primary outcome is peripartum blood transfusion (blood transfusion from delivery to 7 days postpartum). Secondary outcomes include adverse medication reactions, maternal and neonatal hematologic indices, and offspring neurodevelopment. Ethics and disseminationA central ethical review board—Advarra—granted ethical approval (Pro00060930). Participating centers—Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of Ethics and dissemination: A central ethical review board—Advarra—granted ethical approval (Pro00060930). Participating centers—Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of.