Low Molecular Weight Iron Dextran Research Articles

Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting

Practitioners often avoid administering iron dextran in parenteral nutrition (PN) for hospitalised children because of the concern for anaphylaxis. The primary aim of the present study was to determine the risk of anaphylaxis associated with exposure to PN containing iron dextran in the inpatient setting. Charts were reviewed for all children admitted to The Children's Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received PN containing low molecular weight (LMW) iron dextran. Subject characteristics, primary diagnoses and PN orders were evaluated. The pharmacy adverse events database was queried for adverse drug reactions. Over three years, 89 subjects received PN containing a maintenance dose of LMW iron dextran with a total of 2774 days of exposure. Subjects ranged from two months to 21 years of age and received between 1 and 196 days of PN containing iron dextran. The mean dose of iron dextran in children decreased as the weight category increased from <5 kg (0.21 ± 0.05 mg/kg/day) to ≥40 kg (1.9 ± 0.5 mg/day; P-value for trend <0.005). No anaphylactic reactions occurred in any subjects. PN containing a maintenance dose of LMW iron dextran can be safely administered to hospitalised children, and further studies are need to evaluate the potential to prevent iron deficiency anaemia and the need for additional IV iron infusions.

The available intravenous iron formulations: History, efficacy, and toxicology.

A number of intravenous iron formulations have been developed over the past 65 years which rely on dextran or other compounds to prevent uncontrolled release of free iron to the circulation. High molecular weight dextran was associated with a number of serious adverse reactions and was removed from markets worldwide in 2009. The preponderance of published evidence suggests that the formulations of parenteral iron currently available in the United States, including low molecular weight iron dextran, are all safe and effective and there are no major, clinically important differences among them in terms of either efficacy or safety. For patients with chemotherapy induced anemia or with anemia of end stage renal disease who are being treated with hemodialysis, it is reasonable to use any of the iron formulations, including iron sucrose and ferric gluconate, as frequent patient encounters with health caregivers are a routine part of care and the need to administer multiple low doses of IV iron is not a major disadvantage. However, a single infusion of a total iron dose is as effective and safe when giving iron preparations containing low molecular weight iron dextran, ferumoxytol, iron isomaltoside, or ferric carboxymaltose. Use of a single total dose infusion results in a decreased number of intravenous infusions with a lower cumulative risk for infusion reactions or extravasations, a reduced need for multiple office visits and repeated utilization of medical staff, and increased convenience for physicians and patients.

Iron deficiency: a new alternative when oral iron fails

Iron deficiency is the most common nutritional deficiency worldwide. The estimated prevalence in the US is about 7% among preschool-aged children and 10%-20% among adolescent females. Although most patients will not develop overt anemia, even mild deficiency may cause acute symptoms and result in long-term cognitive defects, underscoring the importance of effective treatment. In theory, correction of iron deficiency is simple: deliver sufficient amounts of bio-available iron to the duodenum and upper jejunum and let nature takes its course. In practice, therapeutic doses of oral iron often are accompanied by unpleasant gastrointestinal symptoms, and the formulations suitable for young children are all unpalatable to some degree. Thus, compliance with oral iron is often poor, and even excellent compliance may be inadequate for individuals with malabsorption or ongoing blood loss. The original parenteral iron formulation, high molecular weight iron dextran, is no longer available in the US due to its relatively high incidence of hypersensitivity reactions. Although low-molecular weight iron dextran is less likely to cause such reactions, test doses and careful monitoring for anaphylaxis are still recommended. Two newer parenteral formulations, iron sucrose and sodium ferric gluconate, are considered relatively safe and are approved for both adults and children, but typically require multiple doses to achieve adequate iron replacement. A newer iron formulation, ferric carboxymaltose, requires no test dose and the recommended infusion time is only 15 minutes. Although not yet approved for pediatric use, it is approved in both Europe and the US for adults “who have intolerance to oral iron or have had unsatisfactory response to oral iron.” In this volume of The Journal, Powers et al report their experience using ferric carboxymaltose in 72 children and adolescents with iron deficiency anemia. Mild, transient side effects were experienced by only 16% of patients, and almost one-half of the subjects required only a single infusion; all but one patient demonstrated improved hematologic values, with two-thirds showing a complete hematologic response. Although expensive compared with other parenteral formulations—all of which, in turn, are much more expensive than oral iron—its convenience and safety profile may make it an attractive option for many patients in whom oral iron therapy is not feasible. Article page 212 ▶ Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral IronThe Journal of PediatricsVol. 180PreviewTo assess the benefits and risks of intravenous (IV) ferric carboxymaltose (FCM) in children with iron deficiency anemia (IDA). Full-Text PDF

CARDIAC DISORDER IN HEMODIALYSIS: BENEFITS OF CHINESE HERBS

Background:A major cause of mortality in hemodialysis patients is cardiac disease. Most complementary and alternative therapies, including Chinese herbal medicine, have been useful in the treatment of cardiac disorders.Materials and Methods:A 46 year old Asian woman with chronic renal failure was admitted to the clinic for hemodialysis. In the course of the fifth session of standard dialysis, she developed shock followed by a ventricular tachycardia which rapidly degenerated into cardiac arrest, from which she was resuscitated through cardio-pulmonary resuscitation. The following therapeutic strategies were applied: low discharge oxygen inhalation; stricter water and salt restriction; dialysate temperature set at 36.0 °C; rhEPO 3000u, per week, low molecular weight iron dextran, 200mg/day, intravenously for five days; the patient received Chinese herbal concoction orally.Results:The patient obtained efficient standard dialysis without any cardiac syndrome.Conclusion:Chinese herbs are useful in the management of cardiac disorders in hemodialysis. Chinese herbs may provide more benefits by adjusting dialysis strategies.

Adolescent fatigue: Is intravenous iron a better solution?

Adolescent fatigue: Is intravenous iron a better solution?

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.

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.

On both sides of the ocean.

On both sides of the ocean.

Safety and efficacy of rapid (1,000 mg in 1 hr) intravenous iron dextran for treatment of maternal iron deficient anemia of pregnancy.

Maternal iron deficiency anemia (IDA) is associated with risk of adverse perinatal outcomes. Oral iron is recommended to reverse anemia, but has gastrointestinal toxicity and frequent non-adherence. Intravenous (IV) iron is reserved for intolerance of, or unresponsiveness to, oral therapy, malabsorption, and severe anemia (1% with hemoglobin [Hgb] levels <7 g/dL). With rare (<100 per one million) adverse events (AEs) ability to infuse a sufficient dose of low molecular weight iron dextran (LMWID) over 60 min, LMWID is an attractive option. This study demonstrated safety and efficacy of rapid IV infusion of 1,000 mg LMWID to gravidas with moderate to severe IDA. An observational treatment study of 1,000 mg LMWID administered over 1 hr for IDA in 189 consecutive, unselected second and third trimester gravidas after oral iron failure was conducted. All received a test dose of 25 mg LMWID and were monitored for AEs during the 60-min infusion. No premedication was administered unless more than one drug allergy or asthma was present in which case IV methylprednisolone was administered. All were followed through pregnancy and delivery. Monitored parameters included Hgb, mean corpuscular volume, serum ferritin, and percent transferrin saturation. About 189 subjects received 1,000 mg LMWID. No serious AEs occurred. About 2% experienced transient infusion reactions. Hgb improved by 1-1.9 g/dL in 82% and ≥2 g/dL in 24%. Second trimester treatment was not associated with greater Hgb improvement than third trimester treatment. Anemia resolved in 95%. Administration of a single large dose of IV LMWID was effective, safe, and convenient. Am. J. Hematol. 91:590-593, 2016. © 2016 Wiley Periodicals, Inc.

Is low-molecular weight iron dextran really the most risky iron?--Unconvincing data from an unconvincing study.

Is low-molecular weight iron dextran really the most risky iron?--Unconvincing data from an unconvincing study.

Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy

Understanding physicochemical properties of intravenous (IV) iron drug products is essential to ensure the manufacturing process is consistent and streamlined. The history of physicochemical characterization of IV iron complex formulations stretches over several decades, with disparities in iron core size and particle morphology as the major source of debate. One of the main reasons for this controversy is room temperature sample preparation artifacts, which affect accurate determination of size, shape and agglomeration/aggregation of nanoscale iron particles. The present study is first to report the ultra-fine iron core structures of four IV iron complex formulations, sodium ferric gluconate, iron sucrose, low molecular weight iron dextran and ferumoxytol, using a cryogenic transmission electron microscopy (cryo-TEM) preservation technique, as opposed to the conventional room temperature (RT-TEM) technique. Our results show that room temperature preparation causes nanoparticle aggregation and deformation, while cryo-TEM preserves IV iron colloidal suspension in their native frozen-hydrated and undiluted state. In contrast to the current consensus in literature, all four IV iron colloids exhibit a similar morphology of their iron oxide cores with a spherical shape, narrow size distribution and an average size of 2nm. Moreover, out of the four tested formulations, ferumoxytol exhibits a cluster-like community of several iron carbohydrate particles which likely accounts for its large hydrodynamic size of 25nm, measured with dynamic light scattering. Our findings outline a suitable method for identifying colloidal nanoparticle core size in the native state, which is increasingly important for manufacturing and design control of complex drug formulations, such as IV iron drug products.

Safety and Efficacy of Rapid (one hour) Single Intravenous Dose Low Molecular Weight Iron Dextran for Treatment of Oral Iron Intolerant Maternal Iron Deficient Anemia

▪ OBJECTIVEDetermine safety and efficacy of rapid (one hour) intravenous infusion of 1,000 mg low molecular weight iron dextran to pregnant women with moderate to severe iron deficient anemia. INTRODUCTIONUp to 70% of pregnant women to whom oral iron is prescribed report significant gastrointestinal side effects. Intravenous iron is an efficient, but often overlooked, therapeutic alternative. METHODSWe conducted an observational treatment study of 1000 mg low molecular weight iron dextran for moderate to severe iron deficient anemia of pregnancy in 189 consecutive, unselected second and third trimester gravidas intolerant of, or unresponsive to, oral iron. All received an intravenous test dose of approximately 25 mg low molecular weight iron dextran. They were then monitored closely for adverse reactions during the balance of a 60 minute infusion. No premedication was administered unless two or more drug allergies or asthma was present in which case prophylactic intravenous methylprednisolone was administered. All subjects were followed through pregnancy and delivery. Monitored parameters included hemoglobin (Hgb), mean corpuscular volume (MCV), serum ferritin, and percent transferrin saturation. RESULTSOne hundred eighty-nine subjects received a single intravenous dose of 1000 mg low molecular weight iron dextran. No first trimester gravidas were treated. No serious adverse events occurred. Minor, self-limited infusion reactions (myalgias or flushing), occurred in 2% of subjects. The mean number of days from treatment to delivery was 58.6 (range 5-190) days. The change in Hgb was positively correlated with the time from treatment to delivery (r2 =0.17, p=0.0039). The initial Hgb was 10.1 g/dl (SD 1.03, SE 0.07) and at delivery 11.5 g/dl (SD=1.04, SE 0.10), with the mean change from diagnosis to delivery of 1.39 g/dl (p<0.0001). An improvement in Hgb was observed in 174 (92% (Figure 1)). In 110 (58%) the observed increment was 1.00-1.99 g/dl (hemoglobin response) and in 45 (24%) ≥ 2.00 g/dl (hematopoietic response). Second trimester treatment was not associated with a greater improvement in Hgb than third trimester treatment. MCV increased by 3.27 femtoliters (fl) for those treated in the second (p<0.0001), and 1.34 in the third(p<0.0001). The mean increment in MCV for those treated in the second trimester was 1.93 fl higher than those treated in the third (p=0.02). Post-partum data were available on 64 (34%). For this subgroup the mean change in Hgb from diagnosis to delivery was 1.48 g/dl, not significantly different than the observed increment for the entire group of 189. From delivery to post-partum follow-up, an additional Hgb increment of 0.66 g/dl was observed (p<0.0001) consistent with sustained iron repletion and post-partum contraction of plasma volume. The increment in Hgb from diagnosis to delivery and diagnosis to post-partum was similar irrespective of trimester of treatment. Anemia resolved in 95%. CONCLUSIONAdministration of a rapid (one hour) single large dose (1000 mg) of intravenous low molecular weight iron dextran is a convenient, effective, well tolerated and safe treatment for maternal iron deficient anemia in women who are intolerant of, or unresponsive to, oral iron. These data are relevant in light of recent publications reporting iron deficient neonates have both delayed growth and development and a statistically significant increment in both cognitive and behavioral abnormalities persisting up to ten years after iron repletion. [Display omitted] DisclosuresOff Label Use: Total dose infusion of low molecular weight iron dextran is off label.

Utilisation des dérivés injectables du fer au cours de la maladie rénale chronique : intérêts, limites et conseils pour un bon usage

Iron deficiency is an important clinical concern in chronic kidney disease (CKD), giving rise to iron-deficiency anaemia, and various impaired cellular functions. Oral supplementation, in particular with ferrous salts, is associated with a high rate of gastro-intestinal side effects and is poorly absorbed, a problem that is avoided with intravenous (IV) irons. Recently, with the approval of the European Medicines Agency's Committee for Medicinal Products for Human Use, the French Agence nationale de sécurité du médicament et des produits de santé (ANSM) took adequate measures to minimize the risk of allergic reactions, by correction on the summary of intravenous iron products characteristics. All IV iron products should be prescribed, administered and injected, inside public or private hospitals exclusively, and a clinical follow-up after the infusion for at least 30 minutes is mandatory. The most stable intravenous iron complexes (low molecular weight iron dextran, ferric carboxymaltose, and iron isomaltoside 1000 [under agreement]) can be given in higher single doses and more rapidly than less recent preparations such as iron sucrose (originator or similars). Test doses are advisable for conventional low molecular weight iron dextrans, but are no more mandatory. Iron supplementation is recommended for all CKD patients with iron-deficiency anaemia and those who receive erythropoiesis-stimulating agents, whether or not they require dialysis. Intravenous iron is the preferred route of administration in haemodialysis patients, with randomized trials showing a significantly greater increase in haemoglobin levels for intravenous versus oral iron and a low rate of treatment-related adverse events during these trials. According ANSM, physicians should apply the product's label recommendations especially the posology. In the non-dialysis CKD population, the erythropoietic response is also significantly higher using intravenous versus oral iron, and tolerability is at least as good. Moreover in some non-dialysis patients, intravenous iron supplementation might avoid or at least delay the need for erythropoiesis-stimulating agents. Following the new ANSM's recommendations, we now have the ability to achieve iron stores replenishment correctly and conveniently in dialysis dependent and non-dialysis dependent CKD patients without compromising safety using the various pharmaceutical forms of iron products especially intravenous compounds.

Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose.

The advantage of the new generation IV iron preparations ferric carboxymaltose (FCM), ferumoxytol (FMX), and iron isomaltoside 1000 (IIM) is that they can be administered in relatively high doses in a short period of time. We investigated the physico-chemical properties of these preparations and compared them with those of the older preparations iron sucrose (IS), sodium ferric gluconate (SFG), and low molecular weight iron dextran (LMWID). Mössbauer spectroscopy, X-ray diffraction, and Fe K-edge X-ray absorption near edge structure spectroscopy indicated akaganeite structures (β-FeOOH) for the cores of FCM, IIM and IS, and a maghemite (γ-Fe2O3) structure for that of FMX. Nuclear magnetic resonance studies confirmed the structure of the carbohydrate of FMX as a reduced, carboxymethylated, low molecular weight dextran, and that of IIM as a reduced Dextran 1000. Polarography yielded significantly different fingerprints of the investigated compounds. Reductive degradation kinetics of FMX was faster than that of FCM and IIM, which is in contrast to the high stability of FMX towards acid degradation. The labile iron content, i.e. the amount of iron that is only weakly bound in the polynuclear iron core, was assessed by a qualitative test that confirmed decreasing labile iron contents in the order SFG≈IS>LMWID≥FMX≈IIM≈FCM. The presented data are a step forward in the characterization of these non-biological complex drugs, which is a prerequisite to understand their cellular uptake mechanisms and the relationship between the structure and physiological safety as well as efficacy of these complexes.

Parenteral iron therapy in the treatment of iron deficiency anemia during pregnancy: a randomized controlled trial.

To compare the efficacy and safety profile of total dose infusion of low molecular weight iron dextran with divided doses of intravenous iron sucrose for the treatment of iron deficiency anemia during pregnancy. Randomized controlled trial. Shifa International Hospital, Islamabad, over a period of two years from January 2008 to December 2009. Pregnant women at gestational age more than 12 weeks with the confirmed diagnosis of Iron Deficiency Anemia (IDA) were divided into two groups. In the group-A, intravenous iron sucrose was given in divided doses while in the group-B, total daily intake of Low Molecular Weight (LMW) of iron dextran was given. Post-infusion Hemoglobin (Hb) was checked at 4 weeks and at the time of delivery for both groups. Paired sample t-test is applied and comparison (in terms of rise in hemoglobin from pre to post) of both groups was not found to be significant. In the group-A (iron sucrose group), mean pre-infusion Hb levels was 9.09 ± 0.83 gm/dl. Mean increase in Hemoglobin (Hb) was 10.75 ± 1.097 gm/dl after 4 weeks of infusion and 11.06 ± 0.866 gm/dl at delivery (p < 0.001). In group-B (iron dextran group) pre-infusion haemoglobin was 8.735 ± 0.956 gm/dl and the mean increase in hemoglobin was 10.613 ± 1.22 gm/dl at 4-week while mean increase of 10.859 ± 1.11 gm/dl at the time of delivery (p < 0.001). Both LMW iron dextran, as well as iron sucrose are equally effective in treatment of IDA during pregnancy, however, LMW iron dextran has the advantage of single visit treatment.

Management of iron deficiency anemia: a survey of pediatric hematology/oncology specialists.

Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology/oncology specialists. A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the US. Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N = 61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N = 335, 84%) dosed at 6 mg/kg/day (N = 248, 62%) divided twice daily (N = 272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N = 327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N = 188) using iron sucrose, 17% (N = 68) ferric gluconate, and 15% (N = 60) low molecular weight iron dextran. The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed.

Safety and Efficacy of Total Dose Infusion of Low Molecular Weight (LMW) Iron Dextran in a Large Population of Anemic Patients Across a Broad Spectrum of Diagnoses Associated with Iron Lack

▪Background: Physicians are reluctant to recommend high dose intravenous (IV) iron infusion for iron deficient (ID) patients due to concerns of adverse events (AEs) including anaphylaxis. This retrospective analysis evaluates efficacy and AEs with LMW iron dextran (ID) total dose infusion (TDI) in patients with iron deficiency.Methods: We retrospectively evaluated the Electronic Medical Records of 468 consecutive patients with iron deficient anemia (IDA) who received IV LMW ID between 01/2008 and 07/2011 in an ambulatory infusion center. Diagnostic parameters for IDA included hemoglobin [Hgb] <11 g/dL, transferrin saturation [TSAT] 19%, ferritin <100 ng/mL. The majority had documented intolerance of or inadequate response to oral iron. All received TDI of LMW ID (1130 ± 217 mg) over 1 hour after a test dose of 25 mg. Pre-medication was not used. Patients were closely monitored for AEs during and immediately after infusions. Laboratory data for baseline and repeat hematological parameters within 8 weeks following infusions were analyzed. End points were safety and efficacy. Safety data was available for all 468 patients. Follow-up data at 8 weeks was available on 315. [Display omitted] Results: There were 103 males and 365 female patients. Most common diagnoses were GI bleed, chemotherapy, menorrhagia and chronic kidney disease. At baseline, mean Hgb was 9.8 g/dL, ferritin 92.08ng/mL, and TSAT 12.37%. At 8 weeks the mean hemoglobin increased to 10.97 g/dL (p =0.0001), Ferritin 279.63 ng/mL (p =0.0001), and TSAT 21.85% (p=0.0001). All tolerated the infusion well. There were no incidents of fever, chills, wheezing, hypotension, stridor, periorbital edema, anaphylaxis or death. One complained of chest tightness, but completed the infusion after several minutes and the administration of diphenhydramine and steroids. One developed a rash. Fatigue and myalgia were reported in 17.31% and 8.33% of patients respectively.Conclusions: This study demonstrates TDI of LMW ID can be given safely and conveniently over 1 hour in an outpatient setting without premedication to ID patients. Easily manageable minor reactions did not affect the therapeutic plan. No allergic or anaphylactic reactions were observed. This study demonstrated TDI of LMW ID improved hemoglobin levels more than 1 g/dL within 8 weeks. Consistent with the preponderance of published evidence TDI of LMW ID should be considered an important therapeutic option for iron replacement in patients with IDA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Intravenous iron administration is associated with reduced platelet counts in patients with chronic kidney disease.

In the management of anaemia associated with chronic kidney disease (CKD), optimal use of intravenous (i.v.) iron has a central role. It minimizes reliance on erythropoiesis-stimulating agents (ESAs) and may be beneficial in reducing overall cardiovascular risks through its effects on platelet counts (PLT). We have examined the effects of i.v. iron on PLT in patients with CKD. Two hundred and three patients with CKD, referred to a single teaching hospital in UK for i.v. iron therapy, received low molecular-weight iron dextran at a median dose of 1000 milligrams given over a median time of 2 h and 40 min. PLT at baseline were compared with the measurements taken during a 4-month follow-up period post-infusion. PLT were checked at various points following i.v. iron treatment. Compared with baseline, mean reduction in PLT ranged between 10.1 and 23.6 (×10(9) /L) during consecutive 15-days intervals post-treatment. At the reference point of 90-days post-infusion, the drop in PLT was statistically significant (P < 0.001). Low molecular-weight iron dextran in patients with CKD leads to reduction in PLT. This reduction appears soon after treatment and is maximal after 3 months. Prospective data are required to confirm these findings and examine whether this translates to a reduction in thrombotic episodes.

Iron repletion is associated with reduction in platelet counts in non-dialysis chronic kidney disease patients independent of erythropoiesis-stimulating agent use: a retrospective cohort study.

BackgroundIron deficiency is common in non-dialysis chronic kidney disease (ND-CKD) patients and, on occasion, requires parenteral iron therapy. We investigated the effect of intravenous iron repletion on platelet counts in ND-CKD patients with and without concomitant darbepoetin administration.MethodsWe conducted a retrospective analysis of ND-CKD patients with iron deficiency anemia treated with low molecular weight iron dextran (LMWID) between 2005 and 2009 at our CKD clinic. The primary end-point was change in platelet count 60 days post infusion of LMWID in those with and without concomitant darbepoetin administration. Secondary end-points were the correlations between changes in platelet count and iron indices.ResultsA total of 108 patients met inclusion and exclusion criteria. The decrease in platelet counts in response to iron repletion was statistically significant (305.72 ± 108.86 vs 255.58 ± 78.97, P = < .0001). The decrease in platelet count was independent of concomitant darbepoetin use. Bivariate regression analysis between baseline platelet count and transferrin saturation by iron (TSAT) showed a negative association (βTSAT = −5.82, P = .0007) and moderate correlation (R = 0.32). Following iron treatment, the within individual changes in platelet count in 60 days were not related to changes in TSAT (βΔTSAT = −0.41, P = .399) and demonstrated a poor correlation (R = 0.10).ConclusionsParenteral iron treatment by LMWID is associated with reduction in platelet counts in iron deficient anemic ND-CKD patients. However, ESA use in the majority of patients prior to intravenous iron administration could have altered platelet production through bone marrow competition.

Safety of total dose iron dextran infusion in geriatric patients with chronic kidney disease and iron deficiency anemia

There are limited data on total dose infusion (TDI) using iron dextran in geriatric chronic kidney disease (CKD) patients with iron-deficiency anemia (IDA). Our goal was to evaluate the safety of TDI in this setting. We conducted a retrospective chart review spanning a 5 year period (2002–2007), including all patients with CKD and IDA who were treated with iron dextran TDI. Patient demographics were noted, and laboratory values for creatinine, hemoglobin and iron stores were recorded pre- and post-dose. TDI diluted in normal saline was administered intravenously over 4-6 hours after an initial test dose. One hundred fifty-three patients received a total of 250 doses of TDI (mean ± SD = 971 ± 175 mg); age was 69 ± 12 years and creatinine 3.3 ± 1.9 mg/dL. All stages of CKD were represented (stage 4 commonest). Hemoglobin and iron stores improved post-TDI (P < 0.001). None of the patients experienced an anaphylactic reaction or death. Adverse events (AEs) were noted in 8 out of 250 administered doses (3.2%). The most common AEs were itching, chills and back pain. One hundred and ten doses of high molecular weight (HMW) iron dextran produced 6 AEs (5.45%), whereas 140 doses of low molecular weight (LMW) iron dextran produced 2 AEs (1.43%), a non-significant trend (P = 0.1433 by Fishers Exact Test). Iron dextran TDI is relatively safe and effective in correcting IDA in geriatric CKD patients. Fewer AEs were noted with the LMW compared to the HMW product. LMW iron dextran given as TDI can save both cost and time, helping to alleviate issues of non-compliance and patient scheduling.