Treatment Of Iron Deficiency Anemia Research Articles

Network pharmacology and molecular docking to explore the mechanism of Sheng Xue Bao mixture against iron deficiency anemia.

Based on network pharmacology and molecular docking, we investigated the mechanism of action of Sheng Xue Bao mixture (SXBM) in treating iron deficiency anemia (IDA). We screened the HERB and traditional Chinese medicine systems pharmacology database and analysis platform databases to identify the active ingredients and targets of SXBM. The targets associated with "iron deficiency anemia" were collected from GeneCards, TTD, and OMIM databases. A component-target interaction network was constructed using Cytoscape 3.8.2. The protein-protein interaction network of candidate targets was generated using the STRING database and visualized with Cytoscape 3.8.2 software. Core modules obtained from clustering analysis were subjected to Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, molecular docking validation of key targets and active components was performed using Autodock Vina software. A total of 174 active components and 111 genes were identified as potential active components and targets for IDA treatment, including quercetin, kaempferol, luteolin, beta-sitosterol, and other flavonoids as main active components. Gene Ontology enrichment analysis show that interleaved genes are enriched in 2328 biological processes, 71 cellular component expression processes, and 157 molecular function processes. Kyoto encyclopedia of genes and genomes analysis mainly envolved Prostate cancer, Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Endocrine resistance, Lipid and atherosclerosis, Central carbon metabolism in cancer, Human cytomegalovirus infection and HIF-1 signaling pathway. STAT3, SRC, PIK3R1, and GRB2 were selected as core targets. The molecular docking results demonstrated strong interactions between key components and their respective target proteins. Network pharmacological analysis suggested that SXBM could treat IDA by regulating various biological processes and related signaling pathways. It laid the foundation for further elucidating the molecular mechanism of SXBM treatment of IDA.

Incidence of Hypophosphatemia After Intravenous Administration of Iron: A Matching-Adjusted Indirect Comparison of Data from Japanese Randomized Controlled Trials.

Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan. A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM. The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95%confidence interval(CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95%CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan. Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe.

A cost-comparative analysis of intravenous Ferric Carboxymaltose versus Iron Sucrose for the ambulatory treatment of Iron-deficiency Anemia in a major tertiary care hospital in Saudi Arabia

<p class="MsoNormal" style="text-align: justify;"><strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">Background:</span></strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;"> The objective of this study was to compare the cost of outpatient ferric carboxymaltose (FCM; Ferinject®) versus Iron sucrose complex (ISC; Ferosac®), two prevalent intravenous iron therapy used in the treatment of iron-deficiency anemia (IDA) in the Kingdom of Saudi Arabia (KSA) from a tertiary care hospital perspective.</span></p> <p class="MsoNormal" style="text-align: justify;"><strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">Methods:</span></strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;"> A retrospective study was performed for all patients who were administered FCM in the outpatient clinical setting at Prince Sultan Military Medical City from January 1, 2019, until December 31, 2019. The descriptive data was analyzed using Microsoft Excel 2019 (Microsoft Corporation, Redmond, WA, USA). The total cost of treatment reflected the cost of drugs, the cost of disposables for each infusion, drug monitoring costs during infusion, the cost of productivity loss, and patient traveling cost.</span></p> <p class="MsoNormal" style="text-align: justify;"><strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">Result:</span></strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;"> Overall, 993 patients with IDA, treated with FCM in 1,688 outpatient visits were recruited in the study. In the outpatient setting, the per annum cost of treatment was SAR 1,434,092.50 with FCM treatment and</span><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi;"> </span><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">SAR 1,715,299.70 with ISC treatment, with a corresponding saving of 16.4% (SAR 281,207.20) with FCM. The cost savings with FCM treatment can be attributed to the reduced frequency of patient visits and corresponding reduction in drug monitoring costs (SAR </span><span lang="EN-GB" style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-fareast-font-family: 'Times New Roman'; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-ansi-language: EN-GB; mso-fareast-language: EN-GB;">266,995.20;</span><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">77.3%), loss of productivity per year (SAR </span><span lang="EN-GB" style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-fareast-font-family: 'Times New Roman'; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-ansi-language: EN-GB; mso-fareast-language: EN-GB;">163,550.20; </span><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">77.3%), and cost of transportation per year (SAR </span><span lang="EN-GB" style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-fareast-font-family: 'Times New Roman'; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-ansi-language: EN-GB; mso-fareast-language: EN-GB;">573,920.00; </span><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">77.3%).</span></p> <p class="MsoNormal" style="text-align: justify;"><strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;">Conclusion:</span></strong><span style="font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif; mso-ascii-theme-font: major-bidi; mso-hansi-theme-font: major-bidi; mso-bidi-theme-font: major-bidi; mso-bidi-language: EN-US;"> The use of FCM, as opposed to ISC resulted in a reduced number of iron infusions (4.4 visits for ISC as compared to one visit for FCM), accompanied by a reduction in the total cost. FCM may represent a cost-saving option compared with the existing alternative therapy used for the management of IDA in KSA.</span></p>

Adherence to ECCO Guidelines for Management of Iron Deficiency and Anemia in Inflammatory Bowel Diseases Among Israeli Adult and Pediatric Gastroenterologists.

The consensus guidelines of the European Crohn's and Colitis Organization (ECCO) for the diagnosis and treatment of iron deficiency anemia (IDA) were published in 2015. We examined the management practices of both adult gastroenterologists (AGs) and pediatric gastroenterologists (PGs) in Israel in treating ID among patients with inflammatory bowel disease (IBD). An 18-question multiple-choice anonymous questionnaire was electronically delivered to AGs and PGs. Questions explored 3 areas of interest: physician demographics, adherence to ECCO guidelines, and management practices of IDA in patients with IBD. Completed questionnaires were returned by 72 AGs and 89 PGs. Practice setting and years of practice were similar. A large majority of AGs and PGs (89% and 92%, respectively) measure complete blood count (CBC) and serum ferritin (S-Fr) at least every 3 months in outpatients with active IBD, as recommended by the ECCO guidelines. In contrast, in IBD patients in remission, only 53% and 26% of AGs and PGs, respectively ( P < 0.001), reported adherence to ECCO guidelines, measuring CBC and S-Fr every 6 months. The ECCO treatment guidelines recommend that intravenous (IV) iron should be considered the first-line treatment in patients with clinically active IBD, with previous oral iron intolerance and those with a hemoglobin level <10 g/dL. Study results indicate that only 43% of AGs recommend IV iron for these indications, compared to 54% of PGs ( P > 0.1). In this study we have demonstrated a relatively low level of adherence to ECCO guideline recommendations among both AGs and PGs, regarding the management of IDA in patients with IBD.

Optimizing diagnosis and treatment of iron deficiency and iron deficiency anemia in women and girls of reproductive age: Clinical opinion.

Iron deficiency (ID) is the world's most common disorder and one of the top five causes of years lived with disability. Whereas low serum ferritin is diagnostic of ID, ferritin-an acute phase reactant-may be elevated in inflammatory states and the first trimester of pregnancy even if ID exists. Consequently, in early pregnancy or chronic inflammation, percent transferrin saturation (TSAT) measurement is the best indicator of iron status. Unfortunately, current guidelines do not recommend routine screening for ID in either pregnant or nonpregnant women in the absence of anemia. This circumstance should be urgently reviewed based on available data. While oral formulations have long been the standard for iron replacement therapy and are widely available and inexpensive, oral iron is frequently associated with adverse gastrointestinal effects for the majority-a major reason for poor adherence, inadequate repletion, and persisting ID symptoms and sequellae. Although safe intravenous iron administration was introduced in the mid-1950s, formulations with cores binding the elemental iron more tightly became available in the 2000s, allowing complete and safe replacement, even in a single setting. Prospectively acquired neonatology evidence reports oral iron's failure to reach the developing fetus when the mother is iron deficient. Consequently, while oral iron remains frontline in the first trimester because of insufficient safety data for intravenous iron, the author recommends that the intravenous route should be the gold standard for second-trimester ID when hemoglobin concentrations are less than 10.5 g/dL and for all iron-deficient women in their third trimester.

Patient-Reported Outcomes After Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study.

Iron deficiency anemia (IDA) is a common cause of fatigue and impaired quality of life. The present study aimed to evaluate the impact of intravenous iron supplementation with ferric carboxymaltose (FCM) on fatigue, physical function, and general health among patients with IDA attending routine clinical care. This was a prospective, single arm, observational study of adult patients prescribed with intravenous FCM for the treatment of IDA during routine clinical care. We used Patient-Reported Outcomes Measurement Information System (PROMIS) instruments to evaluate fatigue (PROMIS Short Form v1.0 13a [FACIT-Fatigue]), general health status (PROMIS Scale v1.2), and physical function (PROMIS Short Form v2.0 4a) before and at 3 and 6 months after FCM treatment. A total of 152 patients were enrolled. Mean age was 47.4 ± 16.0 years and 82.2% were female. Mean serum hemoglobin was 10.2 ± 1.4 g/dL at baseline. All patients were treated with at least one FCM dose at baseline, with 77.6% receiving a two-dose treatment course. The mean baseline FACIT-Fatigue score was 61.0 ± 9.0, improving significantly to 50.2 ± 9.5 at 3 months after FCM treatment. A minimum 5-point improvement, pre-defined as clinically meaningful, was seen in the FACIT-Fatigue, PROMIS Global Physical Health, Global Mental Health and PROMIS Physical Function scores for 72.7%, 52.8%, 41.7% and 39.8% of patients at 3 months (p < 0.0001 for each change from baseline), with statistically significant improvement continuing at 6 months. Mean serum hemoglobin was significantly increased at both 3 and 6 months (12.8 g/dL [N = 44] and 12.4 g/dL [N = 54], respectively). IDA patients attending routine clinical practice reported substantial levels of fatigue and impairments in physical function and global health prior to intravenous iron treatment. Patients experienced significant improvements in fatigue symptoms, physical function, and global health at 3 months after treatment with FCM, which were sustained at 6 months.

Quantification of Leghemoglobin Extracted from Roots of Five Different Alfalfa (Medicago sativa) Cultivars: An Experimental Study

Background: Leghemoglobin is an oxygen transporter and a hemoprotein found in nodule roots of nitrogen fixator plants from Leguminosae family. Leghemoglobin is produced in response to presence of bacteria belonging to Rhizobia family. Structurally, leghemoglobin is similar to hemoglobin and has a kind of heme iron structure. Study of leghemoglobin as a heme iron containing agent can open up a new way for treatment and natural prevention of iron deficiency anemia and substitution with mineral iron salts.&#x0D; Methods: Five different cultivars of alfalfa plants including Esfahani, Bammi, Yazdy, Nik shahri, and Hamedani were cultivated in gardening farm of the faculty of agriculture in Shahid Chamran University in a linear form. Cultivation was done with biological fertilizer containing Sinorhizobium meliloti for test groups and without fertilizer for sham groups. After 60 days, the samples were harvested, and the amount of leghemoglobin produced in nodules was quantified using LaRue and Child fluorometric method.&#x0D; Results: The results from five cultivars of alfalfa planted with biological fertilizer showed a significant increase in viscosity of leghemoglobin in nodules of the test group in comparison with sham group (P&lt;0.0001). Moreover, the high viscosity of leghemoglobin in nodules of Bammi cultivar indicated the capacity of this plant to produce leghemoglobin in Ahvaz.&#x0D; Conclusion: According to the findings of this study, Bammi cultivar of alfalfa is a good option for future studies and even production of high amounts of leghemoglobin in Khuzestan Province.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

Low Serum Hepcidin Levels in Patients with Ulcerative Colitis - Implications for Treatment of Co-existent Iron-Deficiency Anemia.

Ulcerative colitis (UC) is often associated with anemia. Hepcidin, the central regulator of iron homeostasis, is known to be induced by inflammation and suppressed by anemia. It is not clear how hepcidin is affected in those with UC, when both inflammation and anemia may co-exist.Such knowledge may hold implications for treatment. Hematological and iron-related parameters, C-reactive protein (CRP), growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE) (erythroid regulators of hepcidin) levels were estimated in blood from those with UC and in control subjects. Values for hematological and iron-related parameters showed evidence of iron-deficiency and resultant anemia, in patients with UC. The presence of UC was significantly associated with inflammation. Serum levels of ERFE, but not of GDF-15, were significantly higher in patients with UC than in control patients, while hepcidin levels were significantly lower. Serum hepcidin concentrations in patients with UC correlated positively with serum iron, ferritin and GDF-15, and negatively with serum ERFE. The iron status and serum hepcidin levels in UC patients with co-existent anemia were significantly lower and serum ERFE values significantly higher than in those with UC without anemia. The effect of anemia on hepcidin predominated over that of inflammation in patients with UC, resulting in suppressed hepcidin levels. This effect is possibly mediated through erythroferrone. We suggest that a serum hepcidin-guided approach may be useful to guide use of oral iron supplements to treat co-existent iron-deficiency anemia in patients with UC and other chronic inflammatory diseases.

RETRACTED ARTICLE: Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial

RETRACTED ARTICLE: Lactoferrin versus ferrous sulphate for the treatment of iron deficiency anemia during pregnancy: a randomized clinical trial

Utilizing admission ordersets and progress note templates to facilitate Identification and treatment of iron deficiency anemia in the hospitalized heart failure patient.

Utilizing admission ordersets and progress note templates to facilitate Identification and treatment of iron deficiency anemia in the hospitalized heart failure patient.

TO COMPARE INTRAVENOUS FERRIC CARBOXYMALTOSE VERSUS INTRAVENOUS IRON SUCROSE IN POST-PARTUM WOMEN WITH IRON-DEFICIENCY ANEMIA

Objectives: The objective of this study was to compare intravenous ferric carboxymaltose (FCM) versus intravenous iron sucrose in post-partum women with iron-deficiency anemia (IDA). Methods: This was a hospital-based prospective randomized controlled study, comprising 100 post-natal women with IDA with hemoglobin level &lt;11 g/dL admitted in post-natal ward of the Obstetrics and Gynecology Department in SP Medical College, Bikaner, from June 2021 to May 2022. Results: In age, residence, socioeconomic status, the incidence of IDA in both the groups were comparable and is more among rural areas, low socioeconomic status. Improvement in hemoglobin, serum ferritin, and blood indices in both the iron sucrose and FCM groups, but it was faster and greater with ferric carboxymaltose when compared with iron sucrose. Other advantages are large dose administration at 1 time, therefore, lesser total number of doses required in the FCM group as compared to the IS group. Conclusion: FCM is well tolerated, safer, and effective than iron sucrose in treatment of post-natal IDA.

Perceptions and experiences of intravenous iron treatment for anaemia in pregnancy in Malawi: a formative qualitative study

Background: The study objective was to explore opinions, identify experiences, and describe perspectives on the acceptability of intravenous (IV) iron to treat anaemia in pregnancy and identify potential barriers and facilitators of introducing IV iron in the Malawian healthcare system. Methods: We conducted 15 in-depth interviews and two focus group discussions with pregnant women, and seven in-depth interviews with health workers at a community-based health centre in Blantyre and a tertiary hospital in Zomba. Results: Most women who used IV iron treatment during the second trimester of pregnancy reported feeling better and stronger after receiving the intervention. Women perceived that IV iron treatment worked faster and increased their haemoglobin count. However, cultural beliefs that IV iron treatment will cause miscarriage and the perception that study procedures involved Satanism and vampirism practices were barriers to acceptability. Health workers found IV iron treatment easy to administer because it is a single-dose treatment, simultaneously reducing the burden for pregnant women taking daily oral iron tablets. However, health workers expressed concerns about the costs and the need to train health workers before the large-scale implementation and integration of IV iron treatment into Malawi’s routine care. Conclusions: Despite the perceived concerns and challenges experienced in participating in the first IV iron infusion trial in Malawi, participants’ reflections suggest that IV iron infusion is acceptable for treating iron-deficiency anaemia in pregnancy. Participant advocate groups can offer a peer-to-peer education approach to sensitize and engage community members on the benefits of treatment and dispel concerns when the country contemplates integrating IV iron infusion for treating anaemia in pregnancy in Malawi.

Consideration of the Characteristics of Oral Iron Preparations from the Viewpoint of the Mechanism of Nausea and Vomiting

The nausea and vomiting that occur as a result of oral iron administration for the treatment of iron-deficiency anemia (IDA) can cause significant physical and emotional stress in patients. Because iron is absorbed from the intestine as ferrous iron, the most widely used treatment for IDA is oral ferrous agents. However, ferrous forms are more toxic than ferric forms because ferrous forms readily generate free radicals. A randomized, double-blind, active-controlled, multicenter non-inferiority study conducted in Japan showed that ferric citrate hydrate (FC) was just as effective as sodium ferrous citrate (SF) in the treatment of IDA, with a lower incidence of adverse reactions such as nausea and vomiting compared with SF. Animal studies have shown that chemotherapy-induced nausea and vomiting (CINV) involves the release of 5-hydroxytryptamine from enterochromaffin cells by free radicals, and that some chemotherapeutic agents cause hyperplasia of these cells. Enterochromaffin cells also contain substance P, which is known to be also closely related to CINV. We found that administration of SF to rats causes hyperplasia of enterochromaffin cells in the small intestine, whereas FC has no effect on enterochromaffin cells. Oral iron agents may induce nausea and vomiting via the effect of ferrous iron on reactive oxygen species production in the intestine and subsequent enterochromaffin cell hyperplasia. Further research to elucidate the detailed mechanism of enterochromaffin cell hyperplasia induced by ferrous iron preparations is needed to develop a treatment for iron deficiency anemia that causes less gastrointestinal damage.

Neonatal outcomes from a randomized controlled trial of maternal treatment of iron deficiency anemia with intravenous ferumoxytol vs oral ferrous sulfate

Anemia in pregnancy is common worldwide and has known maternal risks. The relationship between the types of treatment offered for maternal anemia and the effects on the fetus and newborn are largely uninvestigated. This study aimed to investigate whether maternal treatment with intravenous ferumoxytol compared to oral ferrous sulfate results in an increase in neonatal hematologic and iron indices. These analyses were planned secondary outcomes and post hoc analysis from the trial with a primary outcome of change in maternal hemoglobin. A randomized controlled trial including 124 participants with anemia by World Health Organization criteria was performed in which participants were allocated in a 1:1 ratio to either 2 infusions of 510 mg of intravenous ferumoxytol or 325 mg oral ferrous sulfate twice daily. Fetal monitoring was performed during each intravenous iron infusion. Standard univariable statistical techniques were used to compare groups and to investigate associations between maternal and neonatal hemoglobin and iron indices. Cord blood hematological parameters were equivalent between groups. Hemoglobin was 15.7 g/dL vs 15.4 g/dL (P=.6) and hematocrit was 50.5% and 49.2% (P=.4) in those randomized to intravenous ferumoxytol and oral ferrous sulfate, respectively. Iron studies revealed higher cord blood ferritin concentrations in infants of participants treated with intravenous ferumoxytol (294 vs 186, P=.005). There were equivalent iron (158 vs 146, P=.4), transferrin (186 vs 196, P=.4) and total iron binding capacity (246 vs 244, P=1) in neonates of participants receiving intravenous vs oral treatment. There were no effects of the infusions observed on cardiotocography. Gestational age at birth was equivalent between groups. We noted a larger birthweight in neonates of participants treated with intravenous ferumoxytol (3215 g vs 3033 g, P=.09), which was not statistically significant. Post hoc analyses revealed a statistically significant correlation between neonatal ferritin and maternal hemoglobin (P=.006) and neonatal ferritin and maternal ferritin (P=.017) at admission for delivery. Neonates of participants who received intravenous ferumoxytol were born with higher ferritin concentrations in cord blood, at the same gestation with the same birthweight. Participants with higher hemoglobin and ferritin indices delivered infants with higher ferritin concentrations in cord blood.

Intravenous infusions of ferumoxytol compared to oral ferrous sulfate for the treatment of anemia in pregnancy: a randomized controlled trial

Iron-deficiency anemia in pregnancy is highly prevalent and presents significant risk to patients. Initial treatment is often with oral medication. We hypothesized that intravenous ferumoxytol would result in superior treatment of anemia as compared to oral ferrous sulfate. This study aimed to investigate whether 2 infusions of intravenous ferumoxytol are superior to the use of twice-daily oral ferrous sulfate for the treatment of iron-deficiency anemia in pregnancy. A randomized controlled trial was performed in which participants with anemic (hemoglobin <11 g/dL and hematocrit <33%) were allocated to receive either 2 infusions of 510 mg of intravenous ferumoxytol approximately 7 days apart, or 325 mg oral ferrous sulfate twice daily from enrollment to the end of their pregnancy. Participants were randomized in a 1:1 ratio to each treatment. Our primary outcome was the change in maternal hemoglobin. Secondary outcomes included maternal iron indices, maternal safety, and maternal tolerability. There were 124 participants (N=62 per group). In the intravenous iron group, the mean change in hemoglobin was 1.86 g/dL (95% confidence interval, 1.57 g/dL-2.14 g/dL) and in the oral group was 0.79 g/dL (95% confidence interval, 0.42 g/dL-1.17 g/dL) (P<.0001). The median change in ferritin between groups was 64.5 (range, 31-364) vs 8 (range, -436 to +167) (P=.0001). The median change in iron between groups was also statistically significant with 47.5 ug/dL (range, -133 ug/dL to +664 ug/dL) in the intravenous group vs 8.5 ug/dL (range, -313 ug/dL to +437 ug/dL) in the oral iron group (P=.001). Intravenous ferumoxytol was well tolerated, and it was associated with statistically significant increases in maternal hemoglobin, hematocrit, iron, and ferritin compared to oral ferrous sulfate.

Iron deficiency and ferroptosis in gynecology. Possible corrections: A review of the literature

The review presents the main aspects of iron deficiency anemia (IDA) in women of reproductive age and highlights current diagnostic methods, therapy, and prevention of IDA. Moreover, the paper presents contemporary views on the molecular mechanisms of iron metabolism and iron homeostasis disruption involved in endometriosis. The role of laboratory tests in the diagnosis of latent and symptomatic iron deficiency of extreme importance was also described. In addition to IDA, anemia also occurs in patients with chronic gynecological diseases with a different pathogenesis. Its mechanisms were reported in the study discussed in the review. The results of the study on ferroptosis in patients with endometriosis were demonstrated, which showed significantly levels of iron, ferritin, lipid hydroperoxide, and low-density lipoprotein were higher in the peritoneal fluid of women with endometriosis than in healthy women. The paper provided current information on the treatment of IDA in gynecology, possible symptomatic hypophosphatemia after intravenous therapy with iron-containing drugs, and methods to treat this complication. Current data on ferroptosis, its effect on the body, and ways of inducing, and inhibiting this process were presented.

#4296 EFFECTS OF FERRIC CITRATE HYDRATE ON FIBROBLAST GROWTH FACTOR 23 AND PLATELET COUNT IN CKD AND NON-CKD PATIENTS WITH IRON DEFICIENCY ANAEMIA

Abstract Background and Aims Iron deficiency increases the transcription and cleavage of the peptide hormone, fibroblast growth factor 23(FGF23). Elevated FGF23 has been associated with increased risk of cardiovascular events and mortality. Iron deficiency also increases platelet count (PLT) in part, and higher levels PLT are associated with arterial thrombosis in the brain. Ferric citrate hydrate (FC, Riona®, Torii Pharmaceutical Co., Ltd. Tokyo, Japan) is an oral iron-based phosphate binder for patients with chronic kidney disease (CKD) and also an iron preparation approved for treatment of iron deficiency anaemia (IDA) in Japan. A phase 3 study was conducted to investigate the efficacy and safety of FC in CKD and non-CKD patients with IDA. This study aimed to evaluate the effects of FC on intact FGF23 and c-terminal FGF23 levels, and the proportion of patients with high PLT (exceeding upper limit: &amp;gt;35.2 × 104/µL). Method A randomized, open-label, multicentre, uncontrolled, 24-week study was conducted at 31 centres in Japan from July 2018 to December 2019 (JapicCTI-184000) in CKD and non-CKD patients with IDA (Hb: ≥8.0 g/dL and &amp;lt;11.0 g/dL, serum ferritin &amp;lt;50 ng/mL in CKD (eGFRcre &amp;lt;60 mL/min/1.73 m2) and &amp;lt;12 ng/mL in non-CKD). CKD patients scheduled to initiate maintenance dialysis were excluded. Dynamic allocation was used to randomise subjects (CKD and non-CKD with Hb at baseline) to the FC-low group (500 mg [approximately 120 mg elemental iron]/day) or FC-high group (1000 mg [approximately 240 mg elemental iron]/day) (1:1). Notably, if investigators determined that sufficient iron replacement had been achieved from week 8 onwards, the study treatment was completed. For this reason, changes from baseline to week 8 were evaluated. Results Of 73 patients (CKD n = 42, non-CKD n = 31), 36 were allocated to the FC-low group (CKD n = 21, non-CKD n = 15) and 37 to the FC-high group (CKD n = 21, non-CKD n = 16). Baseline levels of serum ferritin, transferrin saturation (TSAT), c-terminal FGF23, intact FGF23, and PLT are shown in Table 1. Regardless of CKD status, serum ferritin and TSAT increased. After FC-low treatment, mean changes from baseline to week 8 (95% CI) in serum ferritin and TSAT were 18.8 (13.3, 24.2) ng/mL and 8.1 (4.4, 11.8) % in CKD, 17.5 (13.8, 21.3) ng/mL and 13.8 (8.7, 18.9) % in non-CKD;, they were 28.1 (13.4, 42.7) ng/mL and 8.8 (5.4, 12.1) % in CKD, 15.9 (12.1, 19.8) ng/mL and 19.9 (9.8, 30.1) % in non-CKD. After administration of FC, in both groups, intact FGF23 levels did not change, whereas c-terminal FGF23 levels decreased. Median changes (interquartile range) from baseline to week 8 of c-terminal FGF23 were -58.00 (-227.50, -12.25) RU/mL in CKD and -725.00 (-1124.00, -168.50) RU/mL in non-CKD, and -66.00 (-265.70, -27.00) RU/mL in CKD and -649.50 (-1127.00, -326.65) RU/mL in non-CKD. Serum phosphate did not change regardless of CKD status. At baseline, high PLT was observed in the FC-low group in 1 CKD case (5.0%) and 8 non-CKD cases (53.3%), and in the FC-high group in 3 CKD cases (15.8%) and 8 non-CKD cases (50.0%). In all these patients, PLT reduction to below 35.2 × 104/µL was observed until week 8. Conclusion In patients with IDA, administration of FC increased serum ferritin and TSAT, decreased c-terminal FGF23, and normalized PLT in patients with high PLT at baseline regardless of CKD status. FC may decrease the potential risk of cardiovascular events in CKD or non-CKD patients with IDA.

Theranostic Role of Iron Oxide Nanoparticle for Treating Renal Anemia: Evidence of Efficacy and Significance by MRI, Histology and Biomarkers.

(1) Background: Increasing attention has been given to applying nanosized iron oxide nanoparticles (IOPs) to treat iron deficiency anemia (IDA). Chronic kidney disease (CKD) patients who suffer from IDA often need long-term iron supplements. We aim to evaluate the safety and therapeutic effect of MPB-1523, a novel IOPs, in anemic CKD mice and to monitor iron storage by magnetic resonance (MR) imaging. (2) Methods: MPB-1523 was intraperitoneally delivered to the CKD and sham mice, and blood were collected for hematocrit, iron storage, cytokine assays, and MR imaging throughout the study. (3) Results: The hematocrit levels of CKD and sham mice dropped initially but increased gradually to reach a steady value 60 days after IOP injection. The body iron storage indicator, ferritin gradually rose and total iron-binding capacity stabilized 30 days after IOP injection. No significant inflammation or oxidative stress were observed in both groups. By T2-weighted MR imaging, the liver signal intensity gradually increased in both groups but was more pronounced in the CKD group, indicating aggressive utilization of MPB-1523. MR imaging, histology and electron microscopy showed MPB-1523 is liver-specific. (4) Conclusions: MPB-1523 can serve as a long-term iron supplement and is monitored by MR imaging. Our results have strong translatability to the clinic.

Sucrosomial® Iron: An Updated Review of Its Clinical Efficacy for the Treatment of Iron Deficiency.

Iron deficiency (ID) and iron deficiency anemia (IDA) are highly prevalent worldwide. Oral iron salts, especially ferrous sulfate, are commonly used for the treatment of iron deficiency (ID). However, its use is associated with gastrointestinal side effects, thus compromising treatment compliance. Intravenous iron administration is a more costly and logistically complex alternative and is not risk-free, as infusion and hypersensitivity reactions may occur. Sucrosomial® iron is an oral formulation consisting of ferric pyrophosphate conveyed by a phospholipid and sucrester matrix (sucrosome®). Intestinal Sucrosomial® iron absorption is mediated by enterocytes and M cells, through the paracellular and transcellular routes, and occurs mostly as intact particles. These pharmacokinetic properties of Sucrosomial® iron result in higher iron intestinal absorption and excellent gastrointestinal tolerance compared to oral iron salts. The evidence derived from clinical studies supports the use of Sucrosomial® iron as a valid first option for the treatment of ID and IDA, especially for subjects who are intolerant or refractory to conventional iron salts. Newer evidence also demonstrates the effectiveness of Sucrosomial® iron, with a lower cost and fewer side effects, in certain conditions usually treated with IV iron in current clinical practice.