Intravenous Iron Preparations Research Articles

Retrospective Evaluation of Pharmacist Assisted Total-Dose Iron Sucrose Protocol in Patients with Iron Deficiency Anemia

IntroductionIron deficiency anemia (IDA) is the leading cause of anemia in the United States. Although oral iron formulations can correct IDA, they are generally poorly tolerated due to gastrointestinal side effects and may require long term use to maintain normal hemoglobin. Intravenous iron is an alternative to oral iron especially in adults who cannot tolerate or absorb oral iron. Intravenous iron preparations avoid problems of malabsorption and can quickly correct IDA but little data exists on the safety or efficacy in patients without chronic kidney disease (CKD) with or without dialysis, heart failure, uterine bleeding, and inflammatory bowel disease. Long term safety of IV therapy is not well established. At a tertiary midwestern medical center between 2008-2018, a dosing protocol was implemented with staff pharmacists aiding physicians in identifying candidates for total dose infusions (TDI) and calculating iron deficits for patients with IDA. We sought to define the safety and efficacy of IV iron in adult ≥ 18 years old with IDA.MethodsWe conducted a retrospective chart review of patients at a tertiary midwestern medical center from 8/1/14 to 8/1/17. Inclusion criteria includes adult patients ≥ 18 years old who were seen in either the inpatient or outpatient setting who received iron sucrose in doses ≥ 300mg. We excluded patients who were receiving the drug for anemia associated with chronic kidney disease or receiving renal replacement therapy. Data was collected and secured using a standardized data extraction sheet administered via online survey. We extracted demographic information, amount of iron sucrose given, and laboratory values such as discharge hemoglobin, serum iron studies, and liver function tests (prior to and after administration). We assessed physician and nurses' notes from the electronic medical record for the development of adverse effects due to TDI. In patients with a 14 to 28 day follow-up labs in our health-system, we assessed hemoglobin and liver function tests. We compared pre-TDI hemoglobin to follow-up hemoglobin in matched patients using the paired student t -test.ResultsA total of 238 patients received iron sucrose TDI for IDA during the study period. 193 patients (81%) were female, and the mean age in our cohort was 60.6 years. Mean weight of our patients was 80.92 Kg. Mean Pre-TDI hemoglobin was 8.76 g/dL. Out of the 238 patients, initial iron studies were completed on 201 patients (88%) with a mean ferritin of 80 ng/mL (range 1.0-607.0 ng/mL) and iron saturation 6.8% (range 1.0-25.0%), respectively. The mean dose of iron sucrose in the total cohort was 680 mg (range 300-2500 mg). Adverse effects attributable to iron sucrose were reported in 15 patients with nausea being the most common effect (7/238, 2.9%). No anaphylaxis episodes were reported unlike prior formulations. Eighty-one patients had accessible labs available between 14 to 28 days. When matching the patients' preadmission and postadmission records, a hemoglobin increase of 2.1 g/L was found (p < 0.001). No increase in liver function tests were found in any patientConclusionsA pharmacist assisted iron sucrose TDI protocol for patients with IDA successfully increased serum hemoglobin and was well tolerated with nausea being the most common side effect. Unlike, prior formulations where anaphylaxis was the most common side effect this was never reported in our patient population, which further proves that newer formulations of IV Venofer have fewer side effects. Pharmacy assisted protocols will increase the number of patients who are identified as candidates and correctly treated for iron deficit with intravenous iron therapy. DisclosuresNo relevant conflicts of interest to declare.

Analiza bolnikov z anemijo zaradi pomanjkanja železa v hematološki ambulanti

Background: Iron deficiency anaemia (IDA) is the most prevalent type of anaemia and a common cause for patient referrals to the haematology outpatient clinic. The aim of this study was to determine the number of patients with IDA treated at the Haematology Outpatient Clinic of the UMC Ljubljana in the period of two years, as well as to inquire into the causes for their referrals to the clinic, patient characteristics, their complete blood count results at initial examination, the prescribed therapy, the number and the causes of their follow-up visits. We draw special attention to the IDA onset mechanism, the microcytic anaemia therapy principles and the indications prompting a referral of an IDA patient to the haematology specialist.Methods: We undertook a retrospective analysis of the medical records of patients who were referred to the Haematology outpatient clinic of the UMC Ljubljana for examination in the two-year period between 1 January 2014 and 31 December 2015 and had been diagnosed with IDA on the basis of their clinical picture and their CBC values. Data were collected with the Hipokrat IT system and statistically evaluated with Microsoft Excel.Results: In the period relevant for our research, 277 patients of those who were referred to the Haematology outpatient clinic for medical examination were diagnosed with IDA. 11.6 % of these patients were male and 88.4 % female; 62.1 % of the female patients were of childbearing age. IDA was specified as the referral diagnosis in the cases of no more than 39 % of the patients referred to the specialist outpatient clinic, whilst the medical condition of the remaining percentage of patients was not identified by the referring doctor. Comorbidities were observed in 50.2 % of the patients, and for 62.5 % of the patients a follow-up appointment was scheduled by the treating haematologist. Of all patients, 63.5 % were treated with an intravenous iron preparation during their first examination at the outpatient clinic and a transfusion of erythrocytes was administered during such an examination to 4.3 % of the patients.Conclusion: Patients with IDA were often treated at our Haematology Outpatient Clinic in the relevant two-year period. The data indicates a poor recognition rate of this prevalent type of anaemia. IDA is not a blood disorder and the referral of IDA patients to the Haematology Outpatient Clinic is justified in the case of severe microcytic anaemia, when the patient does not respond to the oral or intravenous iron replacement therapy or if a concomitant change in the CBC persists despite the effective treatment with iron preparations.

A Prospective Randomised Controlled Trial of a Single Intravenous Infusion of Ferric Carboxymaltose vs Single Intravenous Iron Polymaltose or Daily Oral Ferrous Sulphate in the Treatment of Iron Deficiency Anaemia in Pregnancy

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: −2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: −23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms.In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.

Comparison of efficiency of a new sucrosomal&#x0D; peroral form of iron with intravenous ferrotherapy in the treatment of anemia in inflammatory bowel diseases.

The article describes the role of iron deficiency in the development of anemia in inflammatory bowel diseases (IBD), existing approaches to treatment. The problems of insufficient effectiveness and poor tolerance of standard iron preparations are discussed, which is associated with the presence of malabsorption and chronic inflammation of the intestinal wall. The aim of the work was to determine the effectiveness of a standard approach to treatment with intravenous iron preparations in comparison with the new sucrsomal oral form of iron Sideral Forte in patients with anemia in IBD. The materials of the study included data from 57 patients with anemia and IBD. The results of examination of 28 patients and treatment of 29 patients with anemia and IBD were analyzed, of which 14 received Sideral Forte, 15 intravenous ferrotherapy. According to the results of the study, it is proved that in the IBD hypo-normochromic and micro-normocytic anemia is always associated with a violation of iron metabolism. The results of the application of these groups of iron preparations for 3 months showed a significant increase in the concentration of hemoglobin, serum iron, a more significant effect of the sucrsomal oral iron for normalization of the hemoglobin concentration.

Financial impact of intravenous iron treatments on the management of anaemia inpatients: a 1year observational study.

Background Intravenous (IV) iron preparations bypass the difficulties (malabsorption and side effects) associated with oral iron for the treatment of iron deficiency anaemia (IDA). Ferric carboxymaltose (FCM) can be administered as a single infusion over short periods of time but is more expensive than iron sucrose (IS) when the patients are hospitalized. Objectives To evaluate the appropriateness of FCM prescriptions and to establish the economic impact of this management (including disease coding) compared to the use of IV IS. Setting This study was conducted for inpatients in all departments (orthopaedic department, gastroenterology department and two units of the internal medicine department) where FCM was widely prescribed. Method We retrospectively identified 224 patients, diagnosed with IDA using laboratory parameters and/or disease coding, who received FCM between January and December 2014. Main outcome measure The primary outcome was the rate of appropriateness of FCM prescriptions and the financial impact compared to IV IS. Results 89 Patients were included. The total additional cost for an inappropriate prescription of IV FCM (68% of cases) was of 6053€. The total incremental cost of unsuitable disease coding was estimated at 31,688€. Indications for IV FCM were categorized: intestinal bleeding (31%), malabsorption (17%), intolerance (9%) and refractory to oral iron (7%). The majority of patients (62%) received 1000mg of FCM per week. The average length of hospital stay was of 10days. Conclusion The prescription of IV iron was appropriate in most cases but did not necessarily require FCM. The use of IV IS, in many cases, could present a cost-saving option for inpatients with IDA. The lack of an IDA coding generated incremental costs.

Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease.

Anaemia is the most frequent, though often neglected, comorbidity of inflammatory bowel disease (IBD). Here we want to briefly present (1) the burden of anaemia in IBD, (2) its pathophysiology, which mostly arises from bleeding-associated iron deficiency, followed by (3) diagnostic evaluation of anaemia, (4) a balanced overview of the different modes of iron replacement therapy, (5) evidence for their therapeutic efficacy and subsequently, (6) an updated recommendation for the practical management of anaemia in IBD. Following the introduction of various intravenous iron preparations over the last decade, questions persist about when to use these preparations as opposed to traditional and other novel oral iron therapeutic agents. At present, oral iron therapy is generally preferred for patients with quiescent IBD and mild iron-deficiency anaemia. However, in patients with flaring IBD that hampers intestinal iron absorption and in those with inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice, although information on the efficacy of intravenous iron in patients with active IBD and anaemia is scare. Importantly, anaemia in IBD is often multifactorial and a careful diagnostic workup is mandatory for optimized treatment. Nevertheless, limited information is available on optimal therapeutic start and end points for treatment of anaemia. Of note, neither oral nor intravenous therapies seem to exacerbate the clinical course of IBD. However, additional prospective studies are still warranted to determine the optimal therapy in complex conditions such as IBD.

CURRENT TREATMENT OPTIONS FOR ANEMIA IN PREGNANT WOMEN (LECTURE)

Anemia can be detected in women before pregnancy, during pregnancy, after childbirth, during lactation period, requiring the attention of doctors and clinical and laboratory monitoring. Iron deficiency anemia (IDA) is the most common anemia in pregnant women. Accurate diagnosis is needed, since there are other possible anemias (posthemorrhagic, folate deficiency, anemia of chronic diseases). Modern options of IDA treatment are include the use of oral iron preparations (in 90% of pregnant women), intravenous iron preparations (in 10% of pregnant women), erythropoiesis stimulating agents – ESA (in 2% of pregnant women), and red blood cell transfusions in severe cases (in 3% of pregnant women). The history of creation of intravenous iron complexes in the laboratory of C.F. Hausmann, as well as properties of various intravenous iron complex formulations in the historical aspect of their manufacturing process (ferric gluconate, iron dextran, iron sucrose, ferric carboxymaltose) and the negotiation of adverse events are described. Indications for the use of intravenous iron preparations are the following: severe IDA, ineffectiveness or intolerance of oral iron, the presence of gastric or duodenal ulcer or gastrointestinal surgery in the past, contraindications for red blood cell transfusions, use of ESA. The advantages of intravenous ferric carboxymaltose are the possibility to use the high dose of iron preparation (1000 mg, 1 time per week), no need for test dose, the possibility of intravenous administration in 15 minutes. High efficiency, good tolerability of ferric carboxymaltose in the treatment of IDA are shown. Pharmacoeconomic analysis showed the feasibility of administration of ferric carboxymaltose in comparison with the drug of previous generation (iron sucrose). The use of intravenous iron preparations in the treatment of IDA in pregnant women will allow to minimize red blood cell transfusions and to move to the stage of drug replacement therapy.

Evaluation of the suitability of a Sprague Dawley rat model to assess intravenous iron preparations

The aim of the study was to examine the reproducibility of a rat model to assess the preclinical similarity in safety profiles and tissue accumulation of iron products. Accordingly, the effect of several doses of intravenously administered Venofer® and of Ferrlecit® on blood parameters, and on kidney and particularly liver toxicity were examined in non-anemic Sprague Dawley rats. The different analysis showed neither a clear treatment nor a dose effect after multiple injections. The parameters measured in this rat strain showed some iron induced adverse effects, but these could not be correlated to treatment specific differences. The findings presented in this paper indicate the difficulty to define a useful preclinical model to evaluate iron-based nano-colloidal preparations.

Administration of intravenous iron preparations induces complement activation in anemic patients

Binder of SPerm (BSP) proteins, the main proteins from bovine seminal plasma, are known to partially intercalate into the outer leaflet of the spermatozoa membrane and bind to choline-containing lipids being present therein. This insertion generates a negative effect on semen quality after cryopreservation by inducing an early-stage capacitation of spermatozoa. The assumption of surface properties exhibited by BSP proteins was checked by tensiometry measurements: BSP proteins are highly surface active. This suggests that BSP proteins can reach the interface covered by phospholipids not only by interactions between one and each other but also due to their own surface activity. The insertion of BSP proteins into the lipid domains outer leaflet of spermatozoa was reproduced on a biomimetic system such as Langmuir monolayers. The insertion of BSP proteins can be performed in the compressible fluid domains which contain choline-bearing lipids. Monolayer films were used as well to study the complexation of BSP proteins by two phospholipid assemblies: low density lipoprotein (LDLs) from egg yolk or liposomes produced from egg phospholipids. Irrespective of the phospholipid structure (lipoprotein or liposome), BSP was hindered to alter the structure of the membrane. Only the overall ratio BSP proteins:phosphatidylcholine was important. The difference between the two sequestering agents lies on their surface properties: LDL have a strong tendency to merge with the outer layer whereas liposomes mainly remain in the bulk on the same time scale.

Safety &amp; Efficacy of Intravenous Iron Preparations in Pregnancy: a systematic review

Safety &amp; Efficacy of Intravenous Iron Preparations in Pregnancy: a systematic review

Impact of iatrogenic iron overload on the course of hepatitis C in the dialysis population: A plea for caution.

About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population. Regular loss of blood in the hemodialysis circuit, in routine blood sampling for laboratory tests (for uremia monitoring), and in gut due to uremic enteropathy, invariably results in iron deficiency for which patients are commonly treated with intravenous (IV) iron preparations. Data on the effects of IV iron in hemodialysis patients with hepatitis C are limited (2 studies) and strongly suggest that parenteral iron may contribute to hepatocellular injury. Iatrogenic iron overload is extremely prevalent among hemodialysis population worldwide. Iron overload and toxicity has emerged as one of the most controversial topic in the management of anemia in dialysis patients. Given the known impact of iron in promoting growth and virulence of HCV and the associated liver disease, it is necessary to use iron therapy cautiously and closely monitor plasma markers of iron metabolism and liver iron stores non-invasively by means of MRI to avoid iron overload in this vulnerable population.

Approach to hypersensitivity reactions from intravenous iron preparations

Hypersensitivity reactions (HSRs) to intravenous iron preparations (IVIPs) are well known. With newer preparations, HSRs have become rarer; however, severe reactions may still occur. We retrospectively reviewed records of patients evaluated for HSRs to IVIPs, to determine the safety of controlled re-administration (CRA). Allergological work-up included a detailed history, skin prick tests (SPTs) with IVIP, and basophil activation tests (BATs) in some patients. CRA with an IVIP was carried out if indicated. Thirty-one patients with mild to severe reactions were evaluated. SPTs and BATs were negative in all patients tested. Eighteen CRAs in 15 patients were performed. Twelve patients tolerated the procedure, including three with a previous grade IV HSR. Two developed urticaria and one developed urticaria and dyspnea. The pathophysiology of HSRs to IVIPs remains currently unclear. SPTs and BATs provided no additional information. However, in appropriate situations, CRA under surveillance can be safely performed in most patients.

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Study of Intravenous Ferric Carboxymaltose in Iron Deficiency Anemia in Women attending Gynecological Clinic: Safety and Efficacy

ABSTRACT Introduction Several intravenous iron preparations are available for the treatment of iron deficiency anemia (IDA). Some of these require multiple small infusions to prevent labile iron reactions, while iron dextran (DEX) is associated with a risk of potentially serious anaphylactic reactions. Ferric carboxymaltose (FCM), a non-DEX intravenous iron, is an effective and a safe option, which can be administered in high single doses without serious adverse effects. Objective The objective of the study was to evaluate the efficacy and safety of FCM in the treatment of IDA in gynecological patients. Materials and methods It was an open, single-arm study including 442 women of age more than 18 years with definitive diagnosis of IDA and hemoglobin (Hb) between 4 and 11 gm% from December 2013 to November 2016. Out of these, 25 women were lost to follow-up and were excluded from the study. Intravenous FCM (500—1500 mg) was administered and the improvement in Hb levels and iron stores was assessed after 3 weeks of total dose infusion. Results Out of the 442 women, 417 women were included in the analysis. Most of the women were in the age group of 30 to 39 years. Most of the women had mild anemia as per the World Health Organization (WHO) guidelines. Mean Hb levels significantly increased over a period of 3 weeks after FCM administration. Other parameters like total iron-binding capacity (TIBC), ferritin, and iron also had a significant improvement after FCM administration. No serious life-threatening adverse events were observed after FCM administration. Conclusion Intravenous FCM is an effective and a safe treatment option for IDA and has an advantage of single administration of high doses without serious adverse effects. How to cite this article Mishra V, Roy P, Gandhi K, Hokabaj S, Aggarwal R. Study of Intravenous Ferric Carboxymaltose in Iron Deficiency Anemia in Women attending Gynecological Clinic: Safety and Efficacy. J South Asian Feder Menopause Soc 2017;5(2):71-74.

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk.

BackgroundFerric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM.AimTo characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort.MethodsElectronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included.ResultsThe prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM—OR = 20.8; 95% CI, 2.6–166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation.ConclusionTreatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

Distinct in vitro Complement Activation by Various Intravenous Iron Preparations

Background: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). Methods: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. Results: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. Conclusion: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

Prevalence and management of anemia in pre-dialysis Malaysian patients: A hospital-based study.

Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy. A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013. A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD. The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.

Assessment of Dextran Antigenicity of Intravenous Iron Preparations with Enzyme-Linked Immunosorbent Assay (ELISA).

Intravenous iron preparations are typically classified as non-dextran-based or dextran/dextran-based complexes. The carbohydrate shell for each of these preparations is unique and is key in determining the various physicochemical properties, the metabolic pathway, and the immunogenicity of the iron-carbohydrate complex. As intravenous dextran can cause severe, antibody-mediated dextran-induced anaphylactic reactions (DIAR), the purpose of this study was to explore the potential of various intravenous iron preparations, non-dextran-based or dextran/dextran-based, to induce these reactions. An IgG-isotype mouse monoclonal anti-dextran antibody (5E7H3) and an enzyme-linked immunosorbent assay (ELISA) were developed to investigate the dextran antigenicity of low molecular weight iron dextran, ferumoxytol, iron isomaltoside 1000, ferric gluconate, iron sucrose and ferric carboxymaltose, as well as isomaltoside 1000, the isolated carbohydrate component of iron isomaltoside 1000. Low molecular weight iron dextran, as well as dextran-based ferumoxytol and iron isomaltoside 1000, reacted with 5E7H3, whereas ferric carboxymaltose, iron sucrose, sodium ferric gluconate, and isolated isomaltoside 1000 did not. Consistent results were obtained with reverse single radial immunodiffusion assay. The results strongly support the hypothesis that, while the carbohydrate alone (isomaltoside 1000) does not form immune complexes with anti-dextran antibodies, iron isomaltoside 1000 complex reacts with anti-dextran antibodies by forming multivalent immune complexes. Moreover, non-dextran based preparations, such as iron sucrose and ferric carboxymaltose, do not react with anti-dextran antibodies. This assay allows to assess the theoretical possibility of a substance to induce antibody-mediated DIARs. Nevertheless, as this is only one possible mechanism that may cause a hypersensitivity reaction, a broader set of assays will be required to get an understanding of the mechanisms that may lead to intravenous iron-induced hypersensitivity reactions.

Comparison of intravenous low molecular weight iron dextran and intravenous iron sucrose for the correction of anaemia in pre-dialysis chronic kidney disease patients: a randomized single-centre study in Nigeria.

BackgroundIntravenous low molecular weight iron dextran and iron sucrose have been used for correction of iron deficiency for many years and have been shown to improve anaemia in chronic kidney disease (CKD). However, there is a paucity of head to head comparisons of these parenteral iron preparations. Such comparative efficacy data would be of particular interest in resource-limited African countries, where the majority of CKD patients are unable to afford erythropoiesis-stimulating agents. Therefore, the aim of this study was to compare the effects of these two intravenous iron preparations in pre-dialysis CKD patients.MethodsSixty-seven anaemic pre-dialysis CKD patients were randomized to one of two treatment groups. The low molecular weight iron dextran group (n = 33) received 1000 mg of low molecular weight iron dextran intravenously in four divided doses of 250 mg. The iron sucrose group (n = 34) received 1000 mg of iron sucrose intravenously in five divided doses of 200 mg. Complete blood count, serum creatinine, serum iron, unsaturated iron binding capacity, serum ferritin and transferrin saturation were assessed at baseline. The baseline parameters were repeated in all patients on Day 24. The primary outcome was the proportion of patients achieving a rise in haemoglobin (Hb) concentration of ≥1.0 g/dL after iron therapy.ResultsThere was no significant difference in the proportion of patients achieving the primary end point between both arms of the study: [7 (21.9%) low molecular weight iron dextran versus 11 (32.4%) iron sucrose; relative risk 0.68, 95% confidence interval (CI): 0.19–1.70; P = 0.23]. At Day 24, the mean increase in Hb concentration from baseline was comparable between the two groups: low molecular weight iron dextran 0.4 ± 0.7 g/dL versus iron sucrose 0.6 ± 0.9 g/dL, mean difference 0.2 g/dL (95% CI: −0.26–0.61; P = 0.28). The proportion of patients that experienced at least one or more adverse events was 27.3% in the iron dextran group versus 14.7% in the iron sucrose arm (P = 0.21).ConclusionBoth intravenous low molecular weight iron dextran and intravenous iron sucrose are effective in correcting iron deficiency and anaemia in pre-dialysis CKD patients.

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23

Objective: Iron isomaltoside (Monofer®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA.Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters.Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found.Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.