A COMPARATIVE STUDY OF INTRAVENOUS IRON SUCROSE VERSUS ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA DURING POSTPARTUM PERIOD

Introduction: Anemia is the commonest major contributing factor in maternal mortality and morbidity in developing countries and according to World Health Organization (WHO) criteria, it contributes to 20% of maternal deaths. Anemia in pregnancy defined as hemoglobin level <11 gm/dl (7.45 mmol/L) and hematocrit less than 33% (WHO). Aim: To compare the efficacy of oral iron ferrous sulphate therapy with intravenous iron sucrose therapy in the treatment of iron deficiency anemia during postpartum period. Material & Methods: This was a prospective randomized comparative clinical trial single center study conducted on 200 postpartum women aged >18 years (after normal delivery or LSCS) within 10 days of delivery with Hb level more or equal to 6 gm/dl but less than 10 gm/dl were included in the study. This was a one year study conducted during 1st December 2018 to 30th November 2019. Results : There was a significant increase in the hemoglobin level in both the groups i.e. in IV iron group, from 8.26 ±1.03gm/dl on day 1 to 11.62±0.94gm/dl on day 45 as compared to oral iron group, from 8.24±1.09gm/dl on day 1 to 11.07±1.14gm/dl on day 45; and serum ferritin level from 41.69±40.45ng/ml on day 1 to 77.34±41.60ng/ml on day 45 in IV iron group as compared to the oral iron group from 22.20±8.82ng/ml on day 1 to 31.72±9.72 ng/ml on day 45. So, there was a rapid increase in both hemoglobin and serum ferritin levels in IV iron group as compared to the oral iron group. Conclusion: Intravenous iron sucrose administration increases the hemoglobin level and serum ferritin more rapidly in compare to the oral intake of ferrous sulphate in women with iron deficiency anemia in postpartum women in our study. Keywords: Iron deficiency anemia, Intravenous iron sucrose, Serum ferritin, Maternal mortality.

Intravenous versus Oral iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial

Objective Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. Study Design This open-label RCT randomized patients with IDA (hemoglobin [hgb] <10 g/dL and ferritin <30 ng/mL) at 24 to 34 weeks' to oral iron or single 1,000-mg dose of IV low-molecular weight iron dextran over one hour. The primary outcome was maternal anemia at delivery (hgb < 11 g/dL). Secondary outcomes were mild/moderate or severe adverse reactions, maternal hgb and ferritin at delivery, blood transfusion, gestational age at delivery, birth weight, neonatal hgb and ferritin, and composite neonatal morbidity. Analysis was as per protocol. Results The trial was stopped early for logistical reasons, and the data analyzed as preliminary data to inform a larger, potentially externally funded, definitive trial. Of 55 patients approached, 38 consented. Of these, 15 were withdrawn: 5 received IV iron from their primary obstetrician after being randomized to oral iron and 10 declined to receive IV iron. Of the remaining 23 patients, who were included in the analytic population, 13 received oral iron and 10 received IV iron. The rate of maternal anemia at delivery (hgb < 11 g/dL) was high overall but significantly reduced with IV iron (40 vs. 85%, p = 0.039). Rates of maternal hgb < 10 g/dL were significantly lower in the IV iron group (10 vs. 54%, p = 0.029). There were no severe adverse reactions and similar rates of mild/moderate reactions between groups. Conclusion IV iron reduces rates of anemia at the time of admission for delivery, supporting a larger RCT comparing IV versus oral iron for the treatment of IDA of pregnancy powered for definitive clinical outcomes. However, issues uncovered in this RCT suggest that patient, clinician, and systems-level barriers associated with different IDA treatment modalities must be considered prior to conducting a larger RCT. This study is registered with clinicaltrials.gov with identifier no.: NCT03438227. Key Points

Changes in Hepcidin Levels in an Animal Model of Anemia of Chronic Inflammation: Mechanistic Insights Related to Iron Supplementation and Hepcidin Regulation

We examined changes in hepcidin (closely associated with anemia of chronic inflammation (ACI)) and upstream regulatory pathways after intravenous (IV) iron supplementation in an ACI animal model. ACI was induced in male Sprague-Dawley rats by intraperitoneally administering complete Freund’s adjuvant (CFA). Two weeks after starting CFA treatment, ACI rats received IV iron (CFA-iron) or vehicle (CFA-saline). Three days after IV iron treatment, iron profiles, hepcidin levels, and expression of proteins involved in the signaling pathways upstream of hepcidin transcription in the liver were measured. In CFA-treated rats, anemia with a concomitant increase in the levels of serum inflammatory cytokines and reactive oxygen species occurred. In CFA-iron rats, hemoglobin (Hb) concentration was still lower than that in control rats. In CFA-saline rats, hepatic hepcidin and ferritin levels increased compared with those in control rats and were further increased in CFA-iron rats. In CFA-saline rats, NADPH oxidase- (NOX-) 2, NOX-4, and superoxide dismutase levels in the liver were upregulated compared with those in control rats and their levels were further increased in CFA-iron rats. In CFA-saline rats, activities of the IL-6/STAT and BMP/SMAD pathways were enhanced in the liver compared with those in control rats and their levels were further increased in CFA-iron rats, whereas IL-6 expression remained unaffected after IV iron administration. In HepG2 cells, iron caused phosphorylation of STAT-3 and SMAD1/5 and knockdown of STAT-3 and SMAD1/5 using siRNAs reduced iron-induced hepcidin upregulation to levels similar to those in corresponding control cells. Renal erythropoietin expression and serum erythroferrone concentration were lower in CFA-iron rats than those in control rats. In ACI rats, IV iron supplementation did not recover Hb within three days despite an increase in hepatic ferritin levels, which might be attributable to an additional increase in hepcidin levels that was already upregulated under ACI conditions. Both STAT-3 phosphorylation and SMAD1/5 phosphorylation were associated with hepcidin upregulation after IV iron treatment, and this seems to be linked to iron-induced oxidative stress.

Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: “Can the Promise Be Kept?”

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients’ dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

Overview of Systematic Reviews (SRs) of Erythropoiesis-Stimulating Agents (ESAs) As Standards of Care for Non-Myeloid Cancer Patients with Chemotherapy-Induced-Anemia (CIA)

OBJECTIVES: While chemotherapy is fundamental to the treatment of many cancers, it is associated with adverse events (AEs), including anemia. CIA is linked to many symptoms, including fatigue and cognitive impairment. Most cancer patients receiving chemotherapy experience CIA. ESAs are indicated for treatment of CIA in non-myeloid cancers. Given the extensive data available, we reviewed SRs of the existing evidence on ESAs for treatment of CIA, to assess their relative efficacy and safety. METHODS: A search for published SRs of ESAs for the treatment of CIA in adults with non-myeloid cancers was conducted across seven databases and three online resources, from inception to July 2020. Data were extracted on hemoglobin-related (Hb)-outcomes; mortality; health-related quality of life (HRQoL), iron use, red blood cell (RBC) transfusions, cancer-related outcomes, and serious AEs (SAEs) including thromboembolic events. Risk of bias was assessed by two reviewers using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool. RESULTS: Of 1027 records assessed, 33 records met eligibility criteria; from these, 14 SRs (from 19 publications) were considered core and were extracted. The majority of SRs (n=13) were meta-analyses of randomized, controlled trials. Mortality was evaluated in 9 SRs: 5 reported no difference between ESA vs. control (best supportive care (BSC) and/or placebo and/or no treatment) and 2 reported higher mortality with ESA vs. control (standard care (no iron or oral iron) and/or placebo and/or no treatment). Cancer-related overall survival was not significantly different for ESA vs. control (BSC or placebo) in 2 SRs, or vs. no ESA treatment in 1 SR. Relapse-free, recurrence-free and progression-free survival did not differ between ESA vs. BSC, no treatment, or placebo, according to 1 SR. Two SRs reported a significantly improved change in Hb from baseline for ESA vs. placebo or BSC. Four SRs reported significantly improved hematological response (definitions varied by study) for ESA vs. control (BSC and/or placebo and/or no treatment) (Table). RBC transfusion requirements were reported for 5 treatment comparisons in 12 SRs. For 3 comparisons (ESA vs. control (BSC and/or placebo and/or no treatment); IV iron + ESA vs. standard care; and IV iron + ESA vs. no iron + ESA), there was a consistent statistically significant reduction in transfusion rates with ESA-based treatment. For 2 other comparisons, 1 SR reported no significant difference in transfusion rates with oral iron + ESA vs. no iron + ESA, and 2 SRs found no difference between darbepoetin vs. epoetin. ESA was associated with a requirement for significantly fewer RBC units per patient vs. control (BSC or placebo) in 1 SR. Functional Assessment of Cancer Therapy-Anemia (FACT-An, 6 SRs) and FACT-Fatigue (FACT-F, 7 SRs) were the only HRQoL measures reported. Two SRs reported clinically important improvements in FACT-An with ESA vs. control (BSC and/or placebo); the remaining SRs reported difficulty in interpreting results due to study heterogeneity. Five SRs reported significant improvements in FACT-F with ESA vs. control (BSC and/or placebo and/or no treatment). One SR did not present a meta-analysis, stating that FACT-F results did not differ for ESA vs. placebo groups, and 1 SR reported a significant improvement in FACT-F for IV iron + ESA vs. standard care (no iron or oral iron). Of 2 SRs reporting SAEs, 1 found no difference in incidence for IV iron + ESA vs. standard care (no iron or oral iron) and 1 found significantly greater incidence for ESA vs. no treatment. Of 6 SRs that compared ESA vs. control, 3 reported an increased risk of thromboembolic events with ESAs in the treatment of CIA and 2 reported no significant difference between treatment groups. The remaining SR reported numerically higher incidences of thromboembolic events with ESA vs. control (no statistical comparison). Several outcomes of interest were not reported, including time to first rescue therapy and supplementary iron use. Most SRs did not report on study quality. CONCLUSIONS: In all SRs reporting efficacy, there were improvements in Hb change from baseline, Hb response, and reduction in RBC transfusions for patients with CIA treated with ESAs vs. control. Results were less consistent across SRs for mortality, thromboembolic events, and HRQoL for ESA vs. control. Lack of study quality reporting may affect the strength of these findings. Figure 1 Figure 1. Disclosures Morga: Astellas Pharma Europe Ltd.: Current Employment. Atzinger: Astellas Pharma Inc.: Current Employment. Arber: York Health Economics Consortium Ltd: Current Employment. King: York Health Economics Consortium Ltd: Current Employment. Phalguni: York Health Economics Consortium Ltd: Current Employment. Sanderson: York Health Economics Consortium Ltd: Current Employment. Alexandre: Astellas Pharma Europe B.V.: Current Employment.

Prevalence of Thrombocytopenia Among Iron Deficiency Anemia in Arab Population in Qatar

Prevalence of Thrombocytopenia among Iron Deficiency Anemia in Arab population in Qatar INTRODUCTION / BACKGROUND Iron deficiency anemia is a common cause of anemia, and account for almost half of the causes of all anemias. It is well known and common that iron deficiency anemia can be with thrombocytosis, A study reviewed 450 patients with a diagnosis of anemia between 2002 and 2006 was performed in which 143 of them were having IDA found that 31% of them were having associated thrombocytosis (4). A retrospective study conducted in Turkey found that Iron deficiency anemia and thrombocytopenia found in 13 from 615 patients (2.1%) (5). IDA and thrombocytopenia are found in certain ethnicity where we don t have data from studies about Arab Population. Materials and Methods We retrospectively reviewed the electronic medical records of patients attended hematology/ IV iron room clinics with the diagnosis of IDA over 2 years from the period between December 2017 to December 2019 in Hamad Medical Corporation, Qatar. Complete blood count and iron parameters were collected and analyzed. Thrombocytopenia was defined as Platelet count of less than 150 × 109/L. Statistical analysis was done using mean and SD and paired t test to compare variables after versus before treatment. Depending on previous studies available in the literature, the prevalence of IDA and thrombocytopenia reported from the study done in Turkey (2.1%), based on this we expect the prevalence estimates in Arab population is 3% (with margin of error +/- %) and confidence level 95%, the required sample size needed would be a total of 1744 participants +- 0.8. The adequate sample size was determined using the following statistical equation: Inclusion Criteria: Arab Female who is diagnosed with iron deficiency anemia or iron depleted and receive iron therapy. Exclusion criteria: Extreme age less than 18 and above 65Any chronic organ dysfunction or failurePrevious bariatric surgery or gastrostomyMalignancy (Known or discovered at any time during study follow up) Results: Out of 1752 cases of IDA, 39 cases had thrombocytopenia, (2.2 %) (table 1) with mean age of 41.38. The mean Platelet count was 108 x 10^9 in patients with thrombocytopenia while it was 325 x 10^9 in non-thrombocytopenia patients. Platelets count mean increased to 179 x 10^9 after iron replacement (p &lt; 0.05). Analysis of thrombocytopenia according to nationalities was obtained which showed 28 cases among Qatari's (2.2%), 4.1 % in Egyptians, 3.8% in Yemenis, 3.1% Sudanese, 2.9%,2.7% in Jordanian and Syrian respectively and 1.1% in other nationalities (table 2). Discussion: Qatar is multinational country with large number of expatriates working in it. In our study thrombocytopenia occurred in 39 cases out of 1752 cases included in the study which represent 2.2% of them. Most of our patients were of Qatari nationality 1327 in which 28 cases of thrombocytopenia were found, with 3.8 % in Egyptian the 2nd most common Arab residents in Qatar. Further analysis according to nationalities revealed 3.1%, 2.9%, 2.7% in Yemenis, Sudanese and Jordanian patients, with 1.1% in other patients from other Arab nationalities. Comparison of blood parameters including platelet count before and after iv iron therapy were obtained which showed mean platelet count was 108 x 10^9 which increased to 179 x 10^9 after iron therapy, The mechanisms for the thrombocytopenia associated with IDA are not well established, although iron plays a critical role both in the synthesis of platelets and in the regulation of thrombopoiesis. Other blood parameters including WBC, ANC, Lymphocyte count showed decremental responses after iron therapy with WBC dropped from 6.3 to 6.1, ANC from 3.5 to 2.7 and lymphocyte count from 1.9 to 1.8 in thrombocytopenic patients. Conclusion: The prevalence of thrombocytopenia among IDA in Qatar was 2.2%, which normalized after iv iron therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Pediatric Heart Failure: Cardiac Ejection Fraction with Cardiomyopathy Decreased to 21% in Iron Deficient from 37% in Iron Sufficient Children

Introduction: The overall aim of our study was to determine if iron deficiency has harmful effects on cardiac function in children with chronic heart failure. Heart failure in children is a complex, heterogeneous disorder leading to a final common pathway of cardiomyocyte dysfunction and attrition. Cellular, animal, and human studies have shown that iron deficiency causes cardiomyocyte dysfunction that can be reversed with iron treatment. Cellular studies of human iron-deficient cardiomyocytes have shown that supplemental iron restores impaired contractility and relaxation. Animal studies have found that cardiomyocyte-specific deletions or alterations of critical iron proteins (transferrin receptor 1, hepcidin, ferroportin) produce cardiomyocyte iron deficiency (without anemia) and result in ultimately fatal cardiac dysfunction that can be rescued with intravenous (IV) iron. Over half of adults with chronic heart failure are iron deficient. Meta-analysis of small randomized clinical trials has shown that IV iron significantly reduces recurrent hospitalization, cardiovascular mortality, and all-cause mortality in iron deficient adults with heart failure. European Society of Cardiology, American College of Cardiology and American Heart Association guidelines recommend consideration of IV iron therapy for adult iron-deficient patients with heart failure. The prevalence and consequences of iron deficiency in children with heart failure have not been established. Previously, two small retrospective studies of children with heart failure have reported that 56% to 96% were iron deficient, with increased morbidity and mortality. The goals of our study of children with heart failure were to determine (i) how often iron status is assessed, (ii) the prevalence of iron deficiency, and (iii) the effects of iron deficiency on cardiac function in patients with cardiomyopathy. Methods: We retrospectively reviewed electronic medical records to identify pediatric patients ages 1-21 years old seen at Columbia University Irving Medical Center Pediatric Heart Failure clinic with absolute iron deficiency during 2010-2020. Heart failure was defined as presence of symptoms or systolic dysfunction by echocardiography. Patients were excluded with a history of heart transplant, isolated diastolic failure, or renal failure requiring dialysis. In adults with heart failure, a transferrin saturation &lt;20% has a sensitivity of 94% and a specificity of 84% in identifying absolute iron deficiency, as determined from a bone marrow aspirate, and iron stores were present in 100% of patients with a transferrin saturation ≥30% (Circ Heart Fail. 2018;11:e0045). In children with heart failure, we used these criteria to define absolute iron deficiency as a transferrin saturation &lt;20% and iron sufficiency as a transferrin saturation ≥30%. Patients with an intermediate transferrin saturation are likely a mixture of absolute and functional iron deficiency, and of iron sufficiency and were excluded from our analysis of cardiomyopathy. Cardiac ejection fraction was evaluated by an echocardiogram performed within 3 months of measurement of transferrin saturation. Results: Of 579 patients with heart failure, only 159 (27%) had any type of laboratory iron studies. Of patients with iron studies, 81 (51%) were evaluated as outpatients; 49% as inpatients. The cause of heart failure was cardiomyopathy (52%), congenital heart disease (34%), acute myocarditis (6%), and other (8%). In the 82 patients with heart failure due to cardiomyopathy, 39 (48%) were iron deficient and 16 (20%) iron sufficient. In the iron deficient children with cardiomyopathy, the left ventricular ejection fraction was lower than in the iron sufficient patients (median 21% vs. 37%; p=0.03 (Mann-Whitney); Figure). The groups did not differ significantly with respect to hemoglobin (Figure), sex, age, or New York Heart Association class. Conclusion: We report a clinically important decrease in cardiac ejection fraction in children with heart failure due to cardiomyopathy who have absolute iron deficiency. Potentially, iron treatment could safely and effectively reverse the harmful effect of iron deficiency on heart function and prospective randomized trials of oral and intravenous iron therapy are urgently needed. Measurement of iron status should routinely be included in the evaluation of children with heart failure. Figure 1 Figure 1. Disclosures Neunert: Novartis: Research Funding.

Management of Severe Iron Deficiency Anemia in the Pediatric Emergency Department: A Comparison of IV Iron Vs Transfusions

Introduction: Severe iron deficiency anemia (IDA) is a problem that often presents to the pediatric emergency department (ED). Recently published ASH-ASPHO Choosing Wisely recommendations suggest avoidance of transfusion in hemodynamically stable, asymptomatic children with IDA 1. Little is known about the use of parenteral iron in this pediatric setting. Methods: We undertook a retrospective review of patients with severe IDA treated in the pediatric ED at the Children's Hospital of Eastern Ontario (CHEO) from September 2017 to June 2021. During this period there were an estimated 75000 patients seen annually. Patients with severe IDA were defined as those presenting with hemoglobin (Hb) less than &lt;70 g/L and low mean corpuscular volume. Results: There were 56 patients that met this criterion with presenting Hb ranging from 17-69 g/L (IQR 41- 62). Median age at presentation was 3.75 yrs (IQR 1.68- 15.5), with a bimodal peak at age 1 yr and again in the teen years (Fig 1). 42 (75%) patients were female. The most common causes of IDA were nutritional and heavy menstrual bleeding. 14 (24.6%) received packed red blood cell (PRBC) transfusion with or without parenteral iron (iron sucrose), and 11 (19.3%) were treated with parenteral iron alone. Almost all (55, 98.2%) were prescribed oral iron supplementation. The lower the presenting Hb, the more likely that transfusion or parenteral iron was used as initial therapy (Fig 2). 19 (33.9%) patients were admitted to hospital and 37 (66.1%) were discharged home from the ED. Nine recipients of parenteral iron alone had follow-up at CHEO, six had follow-up within 10 days with Hb increases of at least 20 g/L and all nine patients had follow-up by day 41 showing increases ranging from 20-97 g/L. Three recipients of parenteral iron alone had presenting Hb &lt;30 g/L and by 9 days following ED encounter all three had increased their Hb by at least 20 (20-32) g/L. Three patients were discharged from ED after IV iron, and none presented to the ED again. Six recipients of PRBCs had follow up within 10 days showing Hb increase ranging from 33-62 g/L, only five had follow-up by day 41 showing increases of 42-79 g/L. Five patients received &gt;1 transfusion, and transfused volumes ranged from 5-25 mL/kg. Minor infusion reactions occurred in 2 (17%) recipients of parenteral iron, and no patient was suspected to have anaphylaxis. Four (28.5%) patients experienced minor transfusion reactions to packed cells. One recipient of multiple PRBC transfusions had transfusion-associated cardiac overload (TACO) requiring ICU admission. Conclusions: This study demonstrates that patients with severe IDA can be safely and effectively managed in the ED setting with parenteral iron therapy alone without PRBC transfusion. The use of parenteral iron avoids the potential short and long-term complications associated with transfusion, whilst ensuring rapid restoration of iron stores without the tolerability issues associated with oral iron. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: IV iron sucrose is indicated for treatment of iron deficiency in patients 2 and older with CKD. The use of it outside of this context would be considered off label.

Iron Infusion Reactions: Risk Factors and Real-World Experience

Introduction: Iron deficiency is the most frequent cause of anemia, which afflicts 32.9% of the global population and is a significant cause of morbidity worldwide. Oral iron is the first-line therapy for treating iron deficiency anemia; intravenous(IV) iron is used when oral iron is inappropriate, poorly tolerated or ineffective. The major adverse effect associated with IV iron is infusion-related reactions (IRR), ranging from mild reactions mediated by complement activation-related pseudo-allergy to anaphylaxis. In this study, we sought to determine rates and severity of iron IRR, identify patient characteristics associated with IRR and report strategies for subsequent iron repletion in patients who have IRR. Methods: We conducted a retrospective chart review of all patients older than 18 years who received IV iron from 1/1/2016 to 7/20/2021 in the outpatient Classical Hematology clinic at Yale New Haven Hospital. Demographics, risk factors, details of reactions and follow up were noted. The primary outcomes analyzed included rates and severity of IRR based on nursing and provider documentation and graded according to a previously-published IRR severity classification (Rampton D et al, Haematologica 2014;99:1671). Secondary outcomes included identification of patient characteristics associated with IRR utilizing Chi-square or Fisher's exact test for unadjusted analysis and logistic regression for multivariable analysis (IBM SPSS version 28). Results: A total of 330 patients, including 298 females, received IV iron. The common formulations used were ferumoxytol, iron sucrose and iron dextran with 199 (60.3%), 49(14.8%), and 36 (10.9%) patients, respectively, receiving each of these. Comorbid conditions were present in 317 (96.1%) patients, including 114 (34.5%) with cardiovascular disease (CVS) and 71 (21.5%) with asthma. Beta blocker or angiotensin-converting enzyme inhibitor (ACEI) use was noted in 90 (27.3%) patients. A history of allergies to medications was present in 167 (50.6%) patients while 139 (42.1%) had other non-drug allergies. The common indications for infusion were anemia due to heavy menstrual bleeding (27.6%), gastrointestinal bleeding (17.2%) and pregnancy (6.9%). Iron IRR was noted in 58 (17.6%) patients, of whom 36 (62.1%) had previously tolerated IV iron. Of the 58 patients with IRR, the median age was 40.32 ± 14.6 years; 30 (51.7%) had allergies to medications, 34 (58.6%) had non-drug allergies, and 13 (22.4%) each had a history of CVS or asthma. Beta blocker or ACEI use was found in 12 (20.7%) patients. The reaction manifestations included gastrointestinal in 16 (27.6%) patients, cardiovascular in 24 (41.4%), bronchopulmonary in 34(58.6%), mucocutaneous in 28(48.3%), neurological in 21(36.2%) and autonomic in 30 (51.7%). The severity of reaction was mild in 22 (37.9%) patients, moderate in 23 (39.7%), and severe in 11 (19%). After a reaction, 28 (48.3%) patients subsequently tolerated a different formulation of IV iron, while 14 (24.1%) patients tolerated the same formulation of IV iron at a slower rate with premedication; 5 (8.6%) patients had a subsequent reaction to a different IV iron formulation. Multivariable regression analysis was performed to examine associations of iron IRR with history of allergies to medications, non-drug allergies, asthma, CVS, use of beta blockers or ACEI and sex. In this analysis, a history of non-drug allergies was significantly and independently associated with greater odds of IRR (odds ratio (OR) 2.40, 95% confidence interval (CI): 1.32-4.37, p=0.004) while a history of CVS was associated with lower odds of IRR (OR 0.46, 95% CI: 0.22-0.988, p=0.047). None of the parameters were found to have an association with the severity of IRR. Conclusion: Iron IRR occurred in 17.6% of patients receiving IV iron, with severe reactions occurring in 3.3% of all patients; these rates are higher than those previously reported in literature. A history of non-drug allergies is independently associated with greater odds of IRR, and additional precautions may be indicated to prevent IRR in such patients. An association of CVS with lower odds of reaction may reflect anti-inflammatory effects of widespread aspirin use in these patients. The majority of patients with iron IRR can subsequently tolerate the same or a different formulation of IV iron with slower rates of infusion and premedication. Figure 1 Figure 1. Disclosures Neparidze: Janssen: Research Funding; GlaxoSmithKline: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees.