Iron Deficiency Anemia In Patients Research Articles

Role of BACH1 in multiple myeloma

ABSTRACT Objective Examine Bach1 protein expression in bone marrow biopsy specimens obtained from newly diagnosed multiple myeloma (NDMM) and iron deficiency anemia (IDA) patients. Conduct a thorough analysis to explore the potential connection between Bach1 and the onset as well as treatment response of NDMM. Methods This study investigated Bach1 expression in bone marrow biopsy tissues from NDMM and IDA patients. Immunohistochemical staining and Image-pro Plus software were utilized for quantitatively obtaining the expression level of Bach1 protein. Arrange Bach1 expression levels from high to low, and use its median expression level as the threshold. Samples with Bach1 expression level above the median are categorized as the high-expression group, while those below the median are categorized as the low-expression group. Under this grouping, a detailed discussion was conducted to explore relationship of the Bach1 expression level with the patients’ gender, ISS stage, and survival rate based on the Bortezomib (Btz) therapy. Results Our experiment indicates that the expression level of Bach1 in NDMM patients is significantly higher than in IDA patients. Furthermore, we discovered that patients in the high-expression group exhibit better prognosis compared to those in the low-expression group after Btz-treatment. Bioinformatics analysis further confirms this conclusion. Conclusion By categorizing Bach1 expression level as high and low, our study offers a unique perspective on understanding the relationship between Bach1 and NDMM.

Evaluation of Brainstem Auditory-Evoked Potentials in Infants with Iron Deficiency Anemia

Purpose: To evaluate and compare the brain functions of infants with and without Iron Deficiency anaemia (IDA) electrophysiologically with brainstem auditory potentials (BAEPs). Materials and Methods: BAEP tests were performed on 26 healthy infants and 26 infants with iron deficiency anaemia, aged 6-24 months, who were followed through the Paediatric Haematology Department at SDU Faculty of Medicine. Children were classified as anaemic if their haemoglobin (Hb) level fell below -2 standard deviations for their age. All patients diagnosed with iron deficiency anaemia received 5 mg/kg/day of divalent iron glycine sulphate complex in three doses daily for a duration of 12 weeks, to be taken on an empty stomach. Both group were orally administered Chloral hydrate at a dosage of 50mg/kg prior to the BAEP test to induce sedation. The BAEP was recorded at a sound intensity level of 90 decibels, with a frequency of 10 Hertz, and with click stimuli ranging from 1000 to 2000. The BAEP test was administered to the IDA group before and after treatment, as well as to the control group, with a 3-month interval between tests. Results: 14 (53.8%) of the IDA patients were males, and 16 (61.5%) of the control group were females. Patients with IDA had an average age of 14.4±3.09 months, while the control group patients have an average age of 11.2±4.04 months. Patients with iron deficiency anaemia had lower pre-treatment levels of Hb, Hct, MCV, MCH, MCHC, transferrin saturation percentage, and ferritin compared to the control group, whereas platelet and RDW values were greater (p˂0.001). The study compared the Brainstem Auditory Evoked Potential (BAEP) values of patients with Iron Deficiency Anaemia (IDA) before treatment with those of control patients. The results indicated that the III-V interval, showing nerve conduction time, was significantly prolonged in the pre-treatment BAEPs (p˂0.05). There was no significant difference in interpeak latencies between the control group and patients with iron deficiency anaemia (IDA) following therapy (p˂0.05). Significant differences were found in the I-III, III-V, and I-V interpeak latencies of individuals with iron deficiency anaemia before and after treatment (p

Intravenous iron infusions in pediatric patients: A retrospective review of efficacy and safety.

Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 μg/L, or ferritin concentration between 100 and 300 μg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Roles of ghrelin, hepcidin and HIF-2α in iron metabolism in iron deficiency anemia.

This study investigates the roles of HIF-2α, hepcidin, and ghrelin in iron deficiency anemia (IDA), the most widespread nutritional disorder globally. Fifty IDA patients (18-50years, BMI 19-25) and 40 healthy volunteers were studied. Hemoglobin, ferritin, hepcidin, HIF-2α, and ghrelin levels were analyzed. IDA patients showed lower hemoglobin, ferritin, hepcidin, and ghrelin levels than the control group, but HIF-2α levels were similar. Positive correlations were observed in both groups between hepcidin and HIF-2α (p < 0.001), hepcidin and ghrelin (p < 0.001), and HIF-2α and ghrelin (p < 0.001). Hemoglobin was correlated positively with HIF-2α, and ferritin was correlated positively with HIF-2α in the patient group. The study suggests that the low hepcidin levels in IDA patients enhance iron absorption. The lack of significant HIF-2α level differences may be due to the absence of chronic hypoxia in current hemoglobin levels of IDA patients. Moreover, the low ghrelin levels in patients and the correlations between ghrelin, hepcidin, and HIF-2α in both groups indicate their involvement in iron metabolism.

Ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in patients with NDD-CKD: a systematic review and meta-analysis.

Background: The application of ferric citrate therapy has yielded unexpected benefits in recent years for Chronic kidney disease patients suffering from hyperphosphatemia and iron deficiency -anaemia. Despite this, earlier research on the impact of ferric citrate on NDD-CKD has been contentious. Objective: The goal of the meta-analysis is to evaluate the evidence regarding the advantages and dangers of ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in NDD-CKD patients. Methods: Between the start of the study and June 2022, we searched PubMed, Embase, Cochrane, EBSCO, Scopus, Web of Science, Wan Fang Data, CNKI, and VIP databases for randomised controlled trials of iron citrate for hyperphosphatemia and anaemia in patients with NDD-CKD. For binary categorical data, risk ratios (OR) were employed, and for continuous variables, weighted mean differences The effect sizes for both count and measurement data were expressed using 95% confidence intervals Results: The meta-analysis includes eight trials with a total of 1281 NDD-CKD patients. The phosphorus-lowering effect of ferric citrate was greater compared to the control group (WMD, -0.55, 95% CI, -0.81 to -0.28; I2 = 86%, p < 0.001). Calcium (WMD, 0.092; 95% CI, -0.051 to 0.234; p > 0.05; I2 = 61.9%), PTH (WMD, -0.10; 95% CI, -0.44 to 0.23; I2 = 75%, p > 0.05) and iFGF23 (WMD, -7.62; 95% CI, -21.18 to 5.94; I2 = 20%, p > 0.05) levels were not statistically different after ferric citrate treatment compared to control treatment. Furthermore, ferric citrate increased iron reserves and haemoglobin. The ferric citrate group had considerably greater levels than the controls. Ferric citrate, on the other hand, may raise the risk of constipation, diarrhoea, and nausea. Conclusion: This meta-analysis found that ferric citrate had a beneficial effect in the treatment of NDD-CKD, particularly in reducing blood phosphorus levels when compared to a control intervention. It also shown that ferric citrate has a favourable effect on iron intake and anaemia management. In terms of safety, ferric citrate may increase the likelihood of gastrointestinal side effects.

Detecting Iron Deficiency Anemia in Type C Hospital: Role of RDW and MCV Parameters

Iron deficiency anemia remains a global health problem, which is also a prominent cause of morbidity and mortality of all range of ages. There are three stages of anemia development, and there are some parameters to detect bodily iron status. Transferrin saturation is one of the reliable parameters. Among all hematology parameters, Red Cell Distribution Width (RDW) and Mean Corpuscular Volume (MCV) are two of the most often studied. MCV and RDW are relatively affordable and accessible, most importantly for rural areas with lower socioeconomic status. This was an analytical observational study with a cross-sectional design aimed to determine the correlation between RDW and MCV values with iron deficiency anemia, which was measured by transferrin saturation. A significant correlation was found between RDW, MCV values, and iron deficiency anemia in patients of Mitra Keluarga Cikarang Hospital and Permata Keluarga Hospital, Jakarta with a p-value of &lt;0.05. Sensitivity and specificity for MCV were 75% and 100%, for RDW were 55.45% and 80%, respectively. In conclusion, RDW and MCV parameters can be used as screening instruments for iron deficiency anemia.

Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Association between iron deficiency anemia and subsequent stomach and colorectal cancer diagnosis in Germany

PurposeIron deficiency anemia (IDA) is the most common form of anemia worldwide, resulting in a high burden of disease. Accumulating evidence suggests that IDA is associated with the development of gastrointestinal (GI) cancers.MethodsData from the IDA database (IQVIA) of primary care practices in Germany of adult patients first diagnosed with IDA between January 2005 and December 2021 were retrospectively analyzed and compared with a 1:1 propensity score-adjusted cohort without IDA. Study outcomes were first stomach cancer or colorectal cancer (CRC) diagnosis up to 10 years after the index date as a function of IDA.ResultsA total of 122,502 individuals with IDA and 122,502 individuals without IDA were included. The 10-year cumulative incidence of CRC was 1.4% in the IDA patients compared to 0.8% in the cohort without IDA (p < 0.001). Regression analysis revealed a significant association between IDA and subsequent CRC (HR 2.05; 95% CI 1.83–2.30). Stomach cancer was diagnosed in 0.3% of IDA patients compared to 0.2% in the non-IDA cohort during the 10-year follow-up period (p = 0.002). However, this was significant only in the age group > 80 years (HR 2.73; 95% CI 1.60–4.67) and in men (HR 1.90; 95% CI 1.38–2.61).ConclusionThese findings add to the literature and suggest an association between IDA and GI cancers. The extent to which this association is due to GI bleeding or other pathophysiological processes that may be caused by IDA requires further investigation, particularly experimental studies.

Diagnostic Yield of Small Bowel Videocapsule Endoscopy in Patients with Iron Deficiency Anemia. A Systematic Review and meta-analysis.

Gastrointestinal (GI) bleeding or malabsorption represents the most frequent aetiologies of iron deficiency anemia (IDA). The cause of IDA remains undetermined in ~10% to 20% of patients undergoing upper and lower GI endoscopies. In this scenario, a small bowel examination with videocapsule endoscopy (VCE) is recommended. We performed a systematic review with meta-analysis to evaluate the diagnostic yield of VCE in patients with IDA without overt bleeding, assessing the prevalence of either any lesion or lesions at high potential of bleeding. A computerized literature search was performed using relevant keywords to identify all the pertinent articles published until March 2023. Twelve studies with a total of 1703 IDA patients (Males: 47%; age range: 19-92y) were included in this systematic review. The diagnostic yield of VCE for overall lesions in the small bowel was 61% (95% CI=44-77; 95 CI=97.2-98.1; I2=97.7%). When analyzing only small bowel lesions likely responsible of IDA, the diagnostic yield was 40% (95% CI=27-53; 95% CI=95.3-97; I2=96.3%). VCE plays a relevant role in the diagnostic work-up of patients with IDA without overt bleeding with a satisfactory diagnostic yield.

Association between Iron Indices and Dyslipidemia among Patients with Iron Deficiency Anaemia: A Cross-sectional Study

Introduction: Iron Deficiency Anaemia (IDA) is a major public health problem in India. Iron plays a role in hepatic lipogenesis, being an integral part of some enzymes and transporters involved in lipid metabolism. Since information on the association between iron metabolism and dyslipidemia in adults is limited, it is important to assess the lipid status in iron-deficient patients. Aim: To study the association of iron indices with the lipid profile among patients with iron deficiency anaemia. Materials and Methods: This hospital-based cross-sectional study was conducted at the Department of Paramedical and Health Sciences, Parul Institute of Paramedical and Health Sciences, Faculty of Medicine, Parul University, Vadodara, Gujarat, India, from December 2022 to May 2023. In the present study, 100 IDA patients aged between 25-45 years were included. All the participants underwent different tests including Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein-Cholesterol (HDL-C), and Low Density LipoproteinCholesterol (LDL-C). Furthermore, the association between IDA patients and lipid levels was analysed. The data were statistically analysed using Pearson’s correlation test and Chi-square test. Results: In the present study, out of a total of 100 patients, 38 were males and 62 were females. The majority of IDA patients had lower levels of TC, TG, and LDL-C. Low levels of TC and LDL were found in 52 (83.87%) of females and 30 (78.94%) of males. A total of 28 (73.68%) of males and 52 (83.87%) of females had lower values for TG levels. In contrast to TC and TG, a substantial correlation between Haemoglobin (Hb) levels and HDL-C and LDL-C was found. However, Hb had a positive association with TG, HDL-C, and LDL-C and a negative correlation with TC. These results also suggest a substantial correlation between Serum Iron (SI) and TC, TG, and HDL-C, but not a significant correlation with LDL-C. Conclusion: When observed for dyslipidemia, IDA patients showed significantly lower levels of TC, TG, and HDL-C with respect to their SI levels.

Prevalence and prognostic significance of iron deficiency anemia among heart failure patients: A prospective observational study

ABSTRACT Background: Patients with chronic heart failure (CHF) frequently have associated iron deficiency, which may or may not be associated with anemia. Studies to ascertain the impact of repleting iron in patients with CHF and various other prognostic markers are lacking in Indian patients and the Indian context. Objectives: The objective is to study the prevalence of iron deficiency anemia in patients with CHF and its prognostic significance in predicting major adverse cardiovascular events (MACEs) during 6 months of follow-up along with the role of other clinical and demographic variables. Methodology: A prospective, observational, hospital-based study conducted in a government tertiary medical center in south India on patients admitted with the diagnosis of CHF. Full demographic and clinical characterization and all relevant laboratory investigations including iron profile were done per protocol. The incidence of a MACE (rehospitalization for heart failure or death) and its association with iron deficiency was studied at the end of a 6-month follow-up. Results: A total of 388 patients were followed for 6 months. Out of those, 211 patients (54%) developed composite outcomes. Old age, coronary artery disease, atrial fibrillation, previous heart failure history, chronic kidney disease, and reduced left ventricular ejection fraction were independent predictors of composite outcome. The prevalence of anemia in the study population was 71%, and iron deficiency was 63% (20% absolute and 43% relative). Iron deficiency without anemia was also an independent predictor of the composite outcome. Conclusions: This study highlights the underestimated and neglected burden of iron deficiency in CHF patients in India. It also suggests further large-scale studies to characterize this easily treatable condition better and consider routine testing of iron profiles in future Indian guidelines.

Markers of oxidative stress in children with iron deficiency anemia

BackgroundOxidative stress can occur in iron deficiency anemia (IDA), causing cellular injury. The primary objective of the study was to assess serum malondialdehyde (MDA), protein carbonyl as oxidants and glutathione reductase catalase, superoxide dismutase (SOD), and vitamin C levels as antioxidants in patients with IDA and healthy controls; and secondary objectives were to observe the levels among the mild, moderate and severe category of IDA and their correlations with serum iron and ferritin. Material and methodsFifty-five patients of IDA and 50 healthy controls were enrolled. Diagnosis of IDA was made based on the cut-off values of low hemoglobin as per age, serum iron <30 μg/dL, ferritin <12 ng/mL, and transferrin saturation <16 %. Serum levels of MDA, protein carbonyl, glutathione reductase, catalase, SOD, and vitamin C were estimated. ResultsThe median age of patients and controls was 6 years. IDA patients had significantly raised mean levels of MDA (p < 0.001) and protein carbonyl (p < 0.001) and decreased glutathione reductase (p < 0.001), catalase (p < 0.001), SOD (p = 0.014) and vitamin C (p = 0.010) than controls. Parameters were comparable among mild, moderate, and severe degrees of IDA. Significantly negative correlations of MDA (r = −0. 713, p < 0.001, −0.683 p < 0.001) and protein carbonyl (r = −0.500, p < 0.001, - 0.519, p < 0.001) and positive correlations of glutathione reductase (r = 0.607, p < 0.001, 0.629, p < 0.001), catalase (r = 0.447, p < 0.001, 0.436, p < 0.001), SOD (r = 0.209, p = 0.032, 0.175, p = 0.075) and vitamin C (r = 0.233,p = 0.017, 0.197, p = 0.044) were observed with serum iron and ferritin, respectively. ConclusionOxidative stress exists in patients with IDA, unaffected by the severity of anemia, and has significant correlations with serum iron and ferritin concentrations.

Distinguishing Iron Deficiency Anemia from Anemia of Chronic Disease Using Hematological Measures

Anemia is a serious public health concern in today’s world which is particularly affecting young children, pregnant women, menstruating adolescent girls and women. The two most common causes of anemia are iron deficiency anemia (IDA) and anemia of chronic disease (ACD), often known as anemia of inflammation. This study aim was to assess the levels of certain hematological parameters, including Hemoglobin Estimation, Mean Corpuscular Volume (MCV), Serum Ferritin, Serum TIBC, Erythrocyte Sedimentation Rate and C - reactive protein to clearly differentiate between iron deficiency anemia and anemia of chronic disease. The study was conducted in Department of Medical Lab Technology, Riphah International University, Islamabad from September 01, 2023 to January 01, 2024. A total of 109 samples with 59 of iron deficiency anemia patients and 50 patients of Anemia of chronic disease were assessed for differentiation be these two diseases. The significant level was selected with p-value less than 0.05. Hemoglobin estimation, TIBC, and ESR were significant in our investigation as their p-values were less than 0.05. Hence, it concluded that Hemoglobin estimation, total Iron Binding Capacity and Erythrocyte Sedimentation Rate were Hematological parameters that distinguished between Iron Deficiency Anemia and Anemia of Chronic Disease.

Клинический случай железодефицитной анемии у пациента пожилого возраста с отягощенным сердечно-сосудистым анамнезом

A clinical case of iron deficiency anemia in a patient with chronic heart failure, coronary artery disease after myocardial infarction and coronary artery stenting, which aggravated the course of the underlying disease and worsened the quality of life, is presented. The important role of correction of iron deficiency anemia in patients with pathologies of the cardiovascular system is shown.

Ratio of hemoglobin to mean corpuscular volume: A new index for discriminating between iron deficiency anemia and thalassemia trait.

Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common microcytic and hypochromic anemias. Differentiation between mild TT and early IDA is still a clinical challenge. To develop and validate a new index for discriminating between IDA and TT. Blood count data from 126 patients, consisting of 43 TT patients and 83 IDA patients, was retrospectively analyzed to develop a new index formula. This formula was further validated in another 61 patients, consisting of 48 TT patients and 13 IDA patients. The new index is the ratio of hemoglobin to mean corpuscular volume. Its sensitivity, specificity, accuracy, Youden's Index, area under the receiver operating characteristic curve, and Kappa coefficient in discriminating between IDA and TT were 93.5%, 78.4%, 83.3%, 0.72, 0.97, and 0.65, respectively. This new index has good diagnostic performance in discriminating between mild TT and early IDA. It requires only two results of complete blood count, which can be a very desirable feature in under-resourced scenarios.

Optimizing Preoperative Iron Deficiency Anemia in Patients Undergoing Cardiac Surgery

Background: Preoperative anemia is common in patients undergoing cardiac surgery, with iron deficiency being the most common cause of anemia in these patients. Patients who are anemic in the preoperative setting have worse perioperative outcomes than patients with normal hemoglobin levels including higher rates of red cell transfusions, acute kidney injury, increased length of stay, and increased mortality. At the University of Virginia (UVA) Medical Center, there was no institutional process in place to identify and treat iron deficiency anemia in patients planned to undergo cardiac surgery. Objective: The UVA Perioperative Blood Management Committee is a newly-formed multidisciplinary group consisting of members from the departments of Hematology, Anesthesiology, Thoracic and Cardiovascular Surgery, Perfusion, and Blood Bank who work together to improve perioperative patient outcomes and blood product utilization. We set out to implement a testing algorithm with the purpose of improving the proportion of anemic patients undergoing cardiac surgery who have iron studies performed in the outpatient setting, thereby improving the percentage of patients receiving intravenous (IV) iron preoperatively. Methods: We adapted two published perioperative treatment algorithms (Lin, Hematology Am Soc Hematol Educ Program 2019; Munting and Klein, Anaesthesia 2019) which recommend iron therapy in patients with hemoglobin &amp;lt; 13 g/dL, ferritin &amp;lt; 100 µg/L, and/or transferrin saturation &amp;lt; 20% for our cardiac surgery preoperative clinic. In November 2022, we implemented a reflex test within Epic electronic medical record that automatically sent ferritin, iron, and transferrin for patients with hemoglobin &amp;lt; 13 g/dL to evaluate for iron deficiency. Patients meeting parameters for iron deficiency (ferritin &amp;lt; 30 ng/mL and/or transferrin saturation &amp;lt; 20%) were then scheduled for iron infusions. We compared the percentage of patients undergoing testing for iron deficiency, as well as the percentage of anemic patients receiving iron infusion preoperatively, to those from a six month period prior to our start date. Results: Between May 31, 2022 and October 31, 2022, 19% of cardiac surgery patients at UVA with hemoglobin values &amp;lt; 13 g/dL had iron studies drawn in the three months prior to surgery. After implementing outpatient reflex iron testing, that number increased to 42% between November 2022 and May 2023 (p &amp;lt; 0.001). In the six months prior to implementation, four iron deficient cardiac surgery patients received preoperative IV iron an average of one day prior to surgery. Between November 1, 2022 and May 29, 2023, fifteen patients received IV iron an average of 5.7 days prior to surgery. The patients who received IV iron had lower rates of blood transfusions than anemic patients who did not receive IV iron (53% vs. 65%) and fewer units of blood transfused per patient who received blood (3.1 vs. 5.7). Conclusions: Results from the first seven months of this project suggest that using a standardized testing methodology in the outpatient setting can increase the uptake of iron testing and thereby treatment of iron deficiency anemia in the preoperative setting. Patients who received IV iron had lower rates of blood transfusions and received fewer units of blood on average than anemic patients who did not receive IV iron. We next plan to implement an iron testing strategy in cardiac surgery inpatients to further improve rates of iron testing and iron infusions in this population. We have created an IRB-approved database to study more patient-centered outcomes such as acute kidney injury, stroke, length of stay, readmissions, and mortality to determine if we can detect a measurable impact from IV iron administration in our patient population.

Transferrin and Erythropoietin Increased Levels Correlate with Thrombosis at High Altitude

Living at high altitude involves great interest because of the challenging multiple adaptive responses to a hypoxic environment. Native Bolivian Andeans have lived at an altitude of 4000 m in The Andes mountains for about 14,000 years exposed to a low atmospheric pressure (453 mmHg) and low oxygen concentration (12,7%). It was described Andeans adaptation to high altitude is mainly related to cardiovascular issues (PMID: 29100088), with a low significantly genetic selection in HIF pathway components responsible of erythropoiesis regulation (PMID: 36980912), so that they have adapted to exist with increased hemoglobin concentrations. Thus, Andeans can be prevalent to undergone hematological and thromboembolic disorders. Thrombotic events have been reported to be increased at high altitude, and this recently associated to increased transferrin (Tf) (PMID: 36040436), likewise to increased erythropoietin (Epo) (Amaru, RevMed 2022). Increased Tf were described to be induced by both iron deficiency and hypoxia via HIF (PMID: 9242677). In addition, iron deficiency was postulated to inhibit the function of prolyl hydroxylase 2 (PHD2) in the hydroxylation of HIF-2, necessary for recognition and degradation by VHL (PMID:22304911). Under normal conditions, Tf is bound to fibrinogen at a molar ratio of 4:1, leading to plasma Tf sequestration by fibrinogen and leaving little Tf free in the circulation. While at hypoxia conditions, abnormally upregulated Tf potentiates thrombin, factor XIIa and inhibits antithrombin, inducing hypercoagulability (PMID:36040436). Similarly, increased HIF1a at high altitude increases Tf promoting the transferrin gene expression, which contains HIF-1α binding sites in its enhancer region (PMID:36844187). HIF is a DNA-binding transcription factor for activating expression of Epo gene (PMID:32561149). Epo, in turn, is increased due to the hyperegulation of HIF as expected at low atmospheric pressure environments. Epo activates the hypoxia-inducible factor that leads to Epo synthesis to stimulate red blood cell production, which also increases the demand for iron to synthesize hemoglobin (PMID:21078592). This, added to a decreased iron and increased HIF 1a, gives rise to a hyperregulation of Tf. Epo has been described to have prothrombotic properties and be related to thrombotic events (PMID:10779449; Amaru, RevMed 2022). In this sense, to further observe a correlation of transferrin and erythropoietin increased levels with the risk of thrombotic events at high altitude, we studied patients with erythrocytosis, anemia and polycythemia vera. We analyzed clinical, lab tests and epidemiological data of 920 patients with Chronic Mountain Sickness erythrocytosis (CMS-e) (n=560), anemia (n=372), and Polycythemia Vera (PV) (n=20), all Bolivian Andeans born and residing at 4000 m. Considering at this altitude normal hemoglobin concentrations vary from 14-17 g/dl in women and 15-18 g/dl in men, erythrocytosis condition comprises Hb levels &amp;gt;18 g/dl in women and &amp;gt;19 g/dl in men (Amaru et al, Rev Hematol Mex, 2016); similarly, it embraces Hb &amp;lt;12 g/dl for women and &amp;lt;13 g/dl for men in anemias (PMID: 23317073). Positive JAK F617V tests were corroborated in PV patients. Iron deficiency correlation considered serum ferritin &amp;lt;30 ug/L and MCV &amp;lt;80 fL (Clark et al, Nutrition, 2008). Eco-doppler study records confirmed the occurrence of thrombotic events. Data analysis was performed through Excel 16.29.1 and SPSS program, Chi-squared, Fishers and Pearson tests were done. We observed significative increased Tf levels in erythrocytosis, anemia, and PV patients mainly on those presenting iron levels deficiency. Epo was highly increased in erythrocytosis patients with iron deficiency. These results correlated with the incidence of thrombotic events in erythrocytosis (CMS-e) and anemia patients with iron deficiency. Age was also relevant in both groups. (Table 1). The increase of Epo levels correlated with thrombosis in erythrocytosis and PV patients with iron deficiency (Table 1). Transferrin and Erythropoietin increased levels at high altitude correlated with thrombosis in Chronic Mountain Sickness erythrocytosis and iron deficiency anemia patients. However, Increased Tf did not correlate with thrombosis in PV patients at high altitude. Our data confirm that increased Tf and Epo have prothrombogenic properties in CMS-e, iron deficiency anemia patients at high altitude.

Efficacy, Safety, and Tolerability of Iron Infusions in Pregnant Women: A Retrospective Chart Review

Background: Iron deficiency (ID) is the most common nutritional deficiency in pregnancy. Iron deficiency anemia (IDA) is also known to be a common problem among pregnant women, and it has been associated with maternal morbidity, peripartum complications, and impaired infant development. Pregnant women who have ID or IDA may benefit from iron infusions to optimize their iron stores more rapidly prior to delivery, however per the American College of Obstetricians and Gynecologists, oral iron is recommended first-line agent for IDA in pregnancy and treating ID without anemia (IDWA) in pregnancy is not currently recommended. IV iron for IDA is considered a second-line agent in pregnancy for many reasons: lack of data on the experience of iron infusions in U.S. pregnant women, lack of randomized trials in pregnant women, and FDA prescribing information labels for all iron formulations containing warnings about possible adverse effects. Also, there has been reluctance to prescribe newer iron formulations including Ferric Carboxymaltose (FCM), Ferumoxytol (FM), and Ferric Derisomaltose (FDI). Methods: In this single center case series, pregnant women in their 2nd or 3rd trimesters who had IDWA or IDA received iron infusions in an outpatient infusion center with nurses trained to monitor pregnant patients carefully for infusion reactions. Before the infusions, the women were assessed in a hematology consult for symptoms of ID, including shortness of breath, fatigue, and ice craving/ice chewing, as well as lab testing consistent with ID (ferritin&amp;lt;30 or iron saturation &amp;lt;16%) and anemia (hemoglobin&amp;lt;12). The iron formulation each woman received was determined by her health plan coverage and, in some cases, by her experience with prior iron infusions. Most women with IDWA were prescribed 400-500mg iron and most women with IDA were prescribed 1000mg iron. Two weeks after the final infusion, follow-up iron and blood counts were measured, and symptoms were re-assessed in a follow-up visit. Safety of iron infusions was determined by reviewing frequency of reactions that occurred during infusions (observed) including complement activation-related pseudoallergy (CARPA) and immune-mediated hypersensitivity reactions, as well as transient discomfort within the first few days after iron infusions (assessed by self-reports or reported during follow-up visits), as well as frequency of discontinuing the infusions. Results: 1,383 pregnant women with IDWA (n=69) or IDA (n=1,314) received a total of 2,971 iron infusions between June 2021 and June 2023, including Ferric Derisomaltose (FDI) 1000 mg single dose (n=417), two Ferumoxytol (FM) 510 mg doses (n=510), four Iron Sucrose (IS) 200 mg doses (n=1,661) or two IS 400 mg doses (n=383). No routine pre-medications were used. Among these pregnant women who received iron infusions, 94% reported improvement of one or more symptoms (shortness of breath, fatigue, or ice craving/ice chewing). Two weeks after the final infusion, 87% were found to have iron saturation greater than 15%, 83% were found to have ferritin above 30, and 88% were found to have increased hemoglobin compared to their pre-infusion hemoglobin. The average hemoglobin increase was 1.2 g/dL. IDA patients had higher hemoglobin increases than IDWA patients but similar increases in iron saturation and ferritin, regardless of iron formulation received. Iron infusions were usually well tolerated. The overall incidence of infusion reactions occurring during infusions, including CARPA reactions, was 4.5% (9.8% for FDI, 4.9% for FM, 1.4% for IS 200 mg doses, and 0.5% for IS 400mg doses). Five pregnant women (0.17%) discontinued iron treatments because of infusion reactions. The overall incidence of post-infusion discomfort symptoms was 22.5% (9.5% for FDI, 18.8% for FM, 31.3% for IS 200 mg doses, and 26.7% for IS 400 mg doses), including tiredness, headache, low back pain, leg swelling, or shortness of breath. Two women were evaluated in hospital ER's, one for hypotension during an iron infusion and one for hives after an iron infusion. There were no adverse events that impacted a woman's pregnancy. Conclusions: Iron infusions in pregnant women are effective, safe, and well-tolerated when administered in an outpatient infusion center that has nurses trained to monitor pregnant patients carefully for infusion reactions. For pregnant women who have IDWA or IDA, the benefits of iron infusions likely outweigh the risks.

Efficacy of Vitamin C with Iron Supplementation in Iron Deficiency Anemia Patients: A Systematic Review and Meta-Analysis

Background Oral iron supplementation is one of the mainstays of treatment for iron deficiency anemia (IDA) but can be complicated by poor absorption. Vitamin C is hypothesized to increase the acidity of the GI tract and enhance the conversion of non-absorbable ferric iron (Fe 3+) to its absorbable ferrous (Fe 2+) state for improved absorption and is often prescribed with iron. However, whether vitamin C supplementation translates to clinically relevant differences, such as sufficient improvements in hemoglobin, remains unclear and a synthesis of available evidence is lacking. Therefore, the present systematic review and meta-analysis aims to compare oral iron with or without vitamin C supplementation in patients with IDA. Methods MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials were searched from database inception to July 2023 for randomized controlled trials (RCTs) and non-randomized studies (NRSs) that investigated the use of oral iron supplements with vitamin C compared to oral iron supplements only in patients with IDA. Title &amp; abstract, full text review and data extraction were conducted independently and in duplicate. The primary outcome was the change in serum hemoglobin levels in g/dL. Secondary outcomes include change in serum ferritin, change in transferrin saturation, change in reticulocyte percentage, and incidence of adverse events including constipation, nausea/vomiting, GI upset and poor taste. The Mantel-Haenszel fixed effects model was utilized for the meta-analysis. The calculated effect sizes were represented by odds ratios (OR) and mean differences (MD) for binary endpoints and continuous endpoints, respectively, with 95% confidence intervals (CI). Results 2231 studies were retrieved from electronic databases. 12 RCTs and one prospective cohort study comprising 2240 patients were included. There was a small but statistically significant increase in serum hemoglobin level (MD 0.14 g/dL [95%CI 0.08, 0.20]) and serum ferritin levels (MD 3.23 µg/L [95%CI 1.63, 4.84]) in the iron + vitamin C group compared to the iron only group. There was a greater reduction in serum transferrin saturation associated with vitamin C supplementation (MD -2.01% [95%CI -3.31, -0.71%]) but the pool of evidence consists of only two studies. Reticulocyte percentage (MD 0.22% [95%CI 0.08, 0.36]) was higher in the iron + vitamin C group than in the iron only group. There were no significant differences between the iron + vitamin C group and the iron only group in overall incidence of adverse effects (OR 0.71 [95%CI 0.50, 1.00]), constipation (odds ratio (OR) 0.83 [95%CI 0.35, 1.96]), or nausea/vomiting (OR 0.80 [95%CI 0.52, 1.24]). The risk of GI upset is lower in the iron + vitamin C group (OR 0.40 [95%CI 0.18, 0.92]). Nevertheless, only three primary studies reported on incidence of adverse events. Conclusion The addition of vitamin C to iron supplementation in the management of IDA was associated with a statistically significant, but likely clinically unimportant, increase in serum hemoglobin of 0.14 g/dL. Similarly, a statistically significant increase in serum ferritin levels by 3.23 µg/L was observed, but its clinical relevance remains uncertain. A strength of the present analysis is the number of RCTs included; however, its conclusions are limited by the heterogeneity of interventions (e.g. different formulations/dosage) across studies. Our results do not provide strong evidence for adding vitamin C to iron supplementation.