Iron Dextran Infusion Research Articles

Ironing out the Wrinkles: Low Molecular Weight Iron Dextran and Premedications

Intravenous (IV) iron infusion increases hemoglobin levels and reduces the need for transfusions compared to oral iron in patients with iron deficiency. Low molecular weight iron dextran (LMW ID) has a boxed warning for anaphylactic-type infusion reactions and premedication is commonly given. However, a recent multi-institution cohort study showed similar rates of infusion-related adverse events (AEs) with iron sucrose (4.3%) and iron dextran (3.8%), and a 23-fold higher incidence of AEs among those who received premedication compared with those who did not (38.6% vs 1.7%). There is currently a national shortage of iron dextran. A study during a previous iron dextran shortage in 2016 showed that the increased use of newer IV iron formulations persisted even once the shortage ended. This may in part be due to the concern for infusion reactions, but the use of these formulations comes at a significant cost. An analysis of the US FDA database showed that, based on differences in the average price of iron sucrose and LMW ID, the cost to prevent one life-threatening AE related to the use of LMW ID was estimated to be 5.0-7.8 million dollars. The cost to prevent one LMW ID-related death was estimated to be 33 million dollars. To further evaluate the incidence of infusion reactions and the use of premedication at the University of Kansas Medical Center, we performed a retrospective analysis of all patients who received their first ever infusion of iron dextran between 1/1/2021-12/31/2022. Infusion reactions were characterized as severe if hypoxia (O2<90%), hypotension (<100/80) or hospital admission occurred. Ninety-six patients were identified. 17 (17.7%) were males and 79 (82.3%) were females. There were 49 (51%) Caucasian, 26 (27.1%) African Americans, 12 (12.5%) Hispanic, and 9 (9.4%) others. 8 patients had infusion reaction (8.3%; 95% CI 4.0-15.1%) as determined by review of nursing documentation. Serious infusion reactions with LMW ID were rare (n=2, 2.1%), and neither patient required epinephrine administration nor hospitalization. Patients with history of allergies (n=61, 63.5%) had a higher incidence of AEs compared to those who did not (13.1% [95% CI, 6.4-23.2%] vs 0.0%, P = 0.022). This was even higher in 27 (28.1%) patients with 3 or more allergies (18.5% [95% CI, 7.4-35.9%] vs 0.0%, P = 0.019). In 71 (80.2%) patients who received premedication, there was a lower incidence of AEs compared to those who did not (3.9% vs 26.3%; χ2 = 10.02; P =0.007). The incidence of AEs was compared with individual premedication, and lower incidences were seen in 64 (66.7%) patients with diphenhydramine (3.1% vs 18.8%, χ2 = 6.82; P =0.015), 50 (52.1%) with methylprednisolone (2.0% vs 15.2%, χ2 = 5.48; P =0.022), and 46 (47.9%) with acetaminophen (0.0% vs 16%, χ2 = 8.03; P =0.004). Notably, a variety of premedication combinations and doses were used, indicating a lack of standardization even within a single institution. No patient who received acetaminophen experienced an infusion reaction. By contrast, there was no significant difference in patients receiving famotidine, suggesting that while acetaminophen may be a useful premedication, famotidine may not be beneficial. Further, our data strongly suggests that patients without a history of drug allergies do not require premedication. Our retrospective study demonstrates significant benefit to receiving premedication, which is divergent when compared to previous studies. This may be due to several reasons: the previously mentioned multi-center study included multiple formulations of IV iron, had a much lower rate of premedication (6% vs. 80%), and used a different definition of infusion reaction. In the multi-center cohort study, administration of medications post-iron infusion was used as a surrogate marker of reaction, while in our study it was based on review of nursing documentation. Both our study and the prior multi-center study noted an increased incidence of infusion reactions in patients with a history of allergies, and both demonstrated the rarity of serious reactions. Based on these results and the prior studies indicating the increased cost of other IV iron formulations, consideration of reinstitution of LMW ID with de-escalation of premedication in those without history of drug allergies should be considered once the current drug shortage resolves.

Role of single-dose intravenous iron therapy for the treatment of anaemia after orthopaedic trauma: protocol for a pilot randomised controlled trial

IntroductionOrthopaedic trauma and fracture care commonly cause perioperative anaemia and associated functional iron deficiency due to a systemic inflammatory state. Modern, strict transfusion thresholds leave many patients anaemic; managing this...

Statement of Retraction: Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial

This article refers to:RETRACTED ARTICLE: Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial

SO051PROSPECTIVE OPEN-LABEL EXPLORATIVE RANDOMISED SINGLE CENTRE COMPARATIVE STUDY TO DETERMINE THE EFFECTS OF VARIOUS INTRAVENOUS IRON PREPARATIONS ON HAEMOGLOBIN, HAEMETENICS, MARKERS OF KIDNEY FUNCTION, QUALITY OF LIFE AND SAFETY

Abstract Background and Aims Iron deficiency in Chronic Kidney Disease (CKD) is common. It frequently necessitates the use of intravenous (IV) iron for correction. A number of second and third generation preparations are now in clinical use with potentially increased efficacy and improved safety profiles. Concerns remain regarding the potential impact of intravenous iron on oxidative stress, kidney function, inflammation and endothelial function, which in turn may represent non-traditional cardiovascular risk factors. The aim of this study is to verify whether three different IV iron preparations have similar safety, efficacy and effects on oxidative stress, inflammation, endothelial and renal function in a non-dialysis CKD population in the short term. Method This was a prospective open-label exploratory randomized, single-centre study comparing the efficacy and safety of three parenteral iron formulations (Iron Dextran (ID), Iron Sucrose (IS) and Iron Isomaltoside (IIM)). Patients with established CKD stages 3-5 and ferritin (SF) < 200microg/L and/or transferrin saturation (TS) <20% were recruited. They were randomized in a 1:1:1:1 ratio receiving a single infusion of ID 200mg IS 200mg, or IIM either at a low (200mg) or high dose (1000mg). Follow-up took place at 2 hours, 1 day, 1 week, 1 month and 3 months post-infusion. Response to iron was assessed using haemoglobin, TS and SF. Kidney function (Creatinine (Cr), eGFR) and proteinuria as a marker of injury (protein:creatinine, albumin:creatinine) were monitored. C-reactive protein (CRP) was used as an inflammatory indicator. Arterial response was monitored using Pulse wave velocity (PWVI). Quality of Life was assessed via the SF-36 questionnaire. Adverse events (AEs) were captured throughout the study, recorded for safety analysis and evaluation of relationship to treatment. Data is presented as means and standard error of the mean (SEM). Statistical analysis was carried out using ANOVA. A p value of <0.05 was statistically significant. Results: Forty patients were recruited and randomized ten to each group; 58% of the patients were male. The mean age was 58.8 years (±2.2). TS and SF rose in response to iron. Greater and more lasting ferritin repletion was seen in the group receiving 1000mg of IIM (pre-dose: 69.1 microg/L (±18.4); 3 months: 271.0 microg/L (±83.3)). All IV iron preparations led to a significant but transient rise in TS within the first 2 hours especially IIM 1000 group (17.8% to 98.7%; p-value <0.001) and IS (21.1% to 91.4%; p-value<0.01) to values >90%. These returned to baseline within 1 week. There was no statistical difference in haemoglobin concentration throughout both cumulatively and comparatively. CRP increased within one day but returned to normal values within one week – this was most pronounced with IS (pre-dose CRP: 8.1 (±3.3) 1-day CRP: 36.1 (±27.0); p=0.29). There was no short-term impact on renal function; mean Cr pre-dose: 234.6 umol/L (±16.6), to 216.6umol/L (±16.2) and mean eGFR pre-dose: 28.2 ml/min (±2.2) to 28.5 ml/min (±2.5). Proteinuria following infusion with IV iron was unchanged (pre-dose: 154.2 mg/mmol (±48.4); 2-hours post-dose: 127.5 mg/mmol (±45.2). Arterial stiffness (PWVI) did not increase following IV iron infusion irrespective of preparation or dosage. Quality of Life improved, which was more evident one month following infusion (pre-dose: 47.7 (±3.8); post-dose 54.4 (±4.3). There was one serious AE in the IIM high dose group with a death more than 2 weeks following infusion likely unrelated to infusion. Conclusion Both high and low dose intravenous irons are effective in replenishing the iron stores with significant increase in iron biomarkers. In the short-term there was no impact on kidney function, inflammation or vascular function. Intravenous iron, irrespective of impact on haemoglobin, translates to improvement in quality of life. Larger and more long-term studies are required to further assess safety.

0975 Iron Infusion Protocol For Restless Leg Syndrome In Pediatric Patients

Abstract Introduction Iron dextran protocols have been studied for adults with restless leg syndrome; this study aims to determine the benefit of iron infusions (iron dextran or sucrose) in the improvement or resolution of restless sleep in pediatric patients. Methods IRB approval was granted by New Hanover Regional Medical Center. A retrospective chart review was performed using the hospital’s electronic medical record (EMR). A data report was requested for all pediatric patients who received the iron dextran protocol. Patients who received at least one dose of iron dextran or iron sucrose per the protocol were included. Manual data collection included patient demographics, CBCs, iron panels, the dose of iron they received, polysomnogram results, symptom resolution (as described by the physician), and adverse events. Results Between January 1, 2017 and January 3, 2018, 55 patients received iron dextran per the weight-based protocol. Patients’ ages ranged from 23 months to 17 years and 5 months old. Of the 55 patients, 27 patients (49%) had documented restless leg syndrome and/or symptoms of leg pain or movement during sleep. All patients experienced restlessness or difficulty sleeping prior to the infusion. Of the 27 patients who experienced leg pain, 10 patients (37%) experienced an improvement in their leg pain or restlessness. Fifty-five percent (55%) of patients in this group reported an improvement in sleep symptoms. Conclusion Iron dextran protocols have been studied for adults with restless leg syndrome, but this is the first published data for a weight-based protocol in pediatric patients. While only 27 patients included in this study had a diagnosis of restless leg syndrome or leg pain symptoms, all patients experienced restlessness or other negative sleep symptoms. Overall, most patients with restless leg syndrome experienced an improvement in their leg and sleep symptoms. No patients reported worsening of symptoms. Intravenous iron dextran infusion may greatly improve the quality of life for children with restless leg syndrome or poor sleep quality. With the overall safety of the iron infusions, this protocol’s benefits outweigh their risks and should be considered in this patient population. Support

Iron Deficiency Anemia Caused By Malabsorption from Proton Pump Inhibition

Introduction: Iron deficiency anemia (IDA) not responding to oral iron replacement usually requires a hematologic evaluation. 48 patients taking a proton pump inhibitor (PPI) and not responding to oral iron replacement were found to have an elevated serum gastrin (SG). No patient had gastrointestinal bleeding, gastric resection, bariatric surgery, or menorrhagia. Other causes for iron malabsorption such as celiac disease or helicobacter infection were not present. 94 percent responded to intravenous iron (IV iron). Methods: All patients previously had undergone diagnostic gastrointestinal evaluations. Testing for celiac disease and helicobacter infection was negative. Gastric biopsies did not demonstrate atrophy. Most referrals were from gastroenterologists. Results: 94% responded to IV iron with a rise in their hemoglobin of >/= 2 grams per cent. 83 percent (40/48) were women. Iron dextran (ID) at a fixed dose of 825 mgm was given to 85% of the patients. Twelve of these 41 patients were given a second infusion of ID as the first dose did not produce a satisfactory response. Ferric carboxymaltose and ferumoxytol were each given once at the fixed recommended dose, and second infusions was not necessary. Four patients received iron sucrose at a weight based dose, and a second series of infusions were not necessary. One patient responded to ferumoxytol after a suboptimal response to iron dextran. An elevated SG was defined as >100 pg/mL. The average SG was 370.25 pg/mL (114 to 2101 pg/mL). Hemoglobin rose an average of 3.35 gram% (9.56 to 12.91 gm%). The change in hemoglobin was minus 0.4 to plus 7.0 gm% with a baseline hemoglobin ranging between 6.6 to 14.3 gm% and rising between 9.3 to 16.2 gram%. Ferritin rose an average of 14.8 to 158 ng/mL with baseline ferritin ranging between 3 to 73 ng/mL and rising between 22 to 659 ng/mL The average MCV rose from 75.89 to 84.93 fL with baseline MCV ranging between 61 to 93 fL rising between 69 to 96 fL The average iron saturation rose from 7.49 to 22.89% with baseline saturation ranging between 2 to 34% and rising between 10 to 39%. Discussion: Dietary iron consists of both heme and non heme iron. Heme iron is derived from the hemoglobin and myoglobin in animal food sources such as meat, seafood, and poultry. Heme iron is in the ferrous (II) oxidation state, is easily absorbable, and contributes 10% or somewhat more of total absorbed iron. Non heme iron is in the ferric (III) form and is derived from plants and iron fortified food. Normally 1-2 mgm of iron is absorbed daily. Heme iron is well absorbed after its release by pancreatic enzymes. Non heme iron is less well absorbed and requires acid secretion from gastric parietal cells for the denaturing of ingested proteins and subsequent proteolysis. PPI causes decreased hydrogen ion (H+) production by inhibiting the hydrogen/potassium pump within gastric parietal cells. The elevated SG derives from G cell hyperplasia as a response to the lowered H+ activity caused by PPI. The decreased H+ activity inhibits the release of ferric iron from non animal sources. Iron absorption occurs in the proximal duodenum through the action of a brush border ferrireductase such as duodenal cytochrome B which reduces ferric iron to ferrous iron. With less ferric iron available for reduction less ferrous iron is absorbed, and iron deficiency results. Intravenous iron fully corrected the IDA in 94% of treated patients. Two of the 3 non responders were obese and only received one infusion of ID. Perhaps a second infusion might have been beneficial. However no relation between weight, response, and ID dosing could be detected. Both patients had normal hemoglobins before the iron infusion but were very symptomatic from their iron deficiency. Both patients experienced a rise in their hemoglobin (1.9 gram% and 1.4 gm%). The third non responder actually had a fall in the hemoglobin from 10.5 to 10.1 gm%. No clear explanation was apparent. No clear explanation for the female predominance was apparent. Conclusion: In 2009 119 million prescriptions for PPI were written in the USA. The gastrointestinal literature suggests that anemia from PPI is uncommon. Very likely IDA due to IM from PPI is much more common than recognized and should be considered for any iron deficient patients without evidence for other causes for IDA. Intravenous iron is highly effective. Disclosures No relevant conflicts of interest to declare.

Intravenous Iron for the Treatment of Steroid-Refractory Idiopathic Thrombocytopenic Purpura

Introduction: Idiopathic thrombocytopenic purpura (ITP) is an acquired platelet disorder that is often caused by antibodies against platelet's antigens. Steroids are effective first therapy for ITP. Steroid-refractory ITP is rare and warrant further investigation and treatment. While iron deficiency anemia (IDA) usually presents with thrombocytosis, there are a few reported cases of IDA presenting with unexplained ITP.Objective: We aim to determine whether the use of intravenous (IV) iron improves platelet count in patients with concomitant steroid-refractory ITP and IDA.Methods: We identified five patients with IDA who presented to the St. John Hospital and Medical Center between 1/2010 and 12/2017 with unexplained profound thrombocytopenia. They were initially treated with steroids without success. All patients were then treated with a single infusion of iron dextran to replenish their iron stores.Results: All five patients were African American females of childbearing age and with a history of menorrhagia. All patients had profound iron deficiency defined as iron saturation less than 20% and ferritin less than 15 ng/dL. Four of these patients had profound thrombocytopenia defined as platelets count below 30,000/mm3(table 1). Other causes of thrombocytopenia were ruled out. With IV iron, all patients achieved complete and durable resolution of their thrombocytopenia lasting for at least 6 months (table 2).Conclusion: The exact mechanism of thrombocytopenia that occurs in patients with IDA is unknown. However, it is suggested that it may be related to the alteration in the activity of iron-dependent enzymes in the cells responsible for megakaryopoiesis and thrombopoiesis. We suggest that patients who present with concomitant steroid-refractory ITP and IDA should receive a trial of IV iron before proceeding with more aggressive therapy such as splenectomy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

RETRACTED ARTICLE: Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial

We, the Editor and Publisher of the Journal of Maternal-Fetal and Neonatal Medicine, have retracted the following article: A. M. Darwish, H. A. Fouly, W. H. Saied & E. Farah (2019) Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial, The Journal of Maternal-Fetal & Neonatal Medicine, 32:13, 2214–2220, DOI: 10.1080/14767058.2018.1429396. Since publication, significant concerns have been raised about the integrity of the data and the reported results in the article. Concerns have also been raised about unexplained overlap between this article and another study published previously (online in 2017) by the same corresponding author: A. M. Darwish, E. E. Khalifa, E. Rashad & E. Farghally (2019) Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial, The Journal of Maternal-Fetal & Neonatal Medicine, 32:3, 398–403, DOI: 10.1080/14767058.2017.1379988. Specifically, these two studies contain 27 identical values in the baseline table and 38 identical values in the outcome tables. Upon query, the authors have not provided responses to our concerns or supplied their original data for review. As significant concerns about the integrity of the article remain, we are therefore retracting the article. The authors have been notified of the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial

Study objective: To test safety, efficacy, and cost-effectiveness of total dose infusion (TDI) of low molecular weight (LMW) iron dextran for treatment of iron deficiency anemia (IDA) during pregnancy in comparison to oral ferrous fumarate.Design: Prospective interventional randomized controlled trial (RCT). Design classification. Canadian Task Force II3.Setting: Antenatal clinic and causality unit of a tertiary care referral facility and University Hospital.Patients: A total 66 anemic pregnant women (hemoglobin level between 7–10 g/dl).Intervention: Administration of a LMW iron dextran as a TDI (group A) or Oral iron ferrous fumarate 60 mg elemental iron three times daily (group B) followed by remeasurement of hemoglobin after 4 weeks.Measures and main results: The main outcome measure was clinical and laboratory improvement of anemia after 4 weeks of starting the therapy. Both groups showed a significant clinical improvement of anemia 4 weeks post-therapy. However, the first improvement of symptoms was significantly faster in group A. Complete blood count (CBC) as well as all iron indices were improved in both groups after 4 weeks of therapy, but were significantly better in group A than B. Side effects in group B were mainly gastrointestinal (GIT) while one case of mild hypersensitivity to TDI and another one case of local reaction at the site of injection were reported in group A.Conclusions: It is concluded that despite being equally effective in improving both clinical and laboratory evidence of IDA, TDI allows iron restoration with a single dose faster than oral iron therapy with a reasonable safety profile. It is a good example of office one-stop therapy. Nevertheless, noninvasive selfusage at home is a clear advantage of the cheaper oral iron therapy which makes it the first choice for treating IDA in the second and third trimesters of pregnancy in tolerable cases.Trial registration: ClinicalTrials.gov identifier: NCT03212781.

Effect of treatment with single total-dose intravenous iron versus daily oral iron(III)-hydroxide polymaltose on moderate puerperal iron-deficiency anemia.

BackgroundIron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being.ObjectiveTo determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III)-hydroxide polymaltose.MethodologyA randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III)-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant.ResultsTwo hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III)-hydroxide polymaltose tablets. Approximately 84.0% (237/282) completed the study and were analyzed including 81% (115/142) of those randomized to injectable iron therapy compared to 85.9% (122/142) of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ significantly between cases and controls (95.7% vs 94.3%; P=0.73). Similarly, the mean increases in hemoglobin following either therapeutic route were comparable (1.03±0.56 g/dL for intravenous iron and 0.97±0.46 g/dL for the oral group; P=0.42).ConclusionSingle total-dose intravenous iron for treatment of puerperal iron-deficiency anemia was as effective as daily single doses of ferric iron tablets. For puerperal patients with iron-deficiency anemia in whom compliance with and tolerability of oral iron are not certain, a single total-dose intravenous iron can be safely offered.

Chronic Transfusion and Iron Overload Modify the Mouse Gut Microbiome

BACKGROUND: Although iron is an essential element in critical metabolic pathways of both pathogenic microorganisms and their hosts it is less essential in certain barrier bacteria, such as Lactobacilli. Dietary iron supplementation increases mortality and affects the microbiome in African children, decreasing the abundance of beneficial Lactobacilli. Furthermore, the method of iron repletion influences the microbiome in patients with inflammatory bowel disease.AIM: To determine whether iron status and different methods of iron supplementation/overload affect the gut microbiome in mice.METHODS: Cohorts of iron-deficient, iron-replete, and iron-overloaded wild-type C57BL/6 female mice (n=5 per group) were generated by dietary manipulation and by injection of iron dextran (0.3mg weekly x 6) or RBC transfusion (0.3mL at 60% hematocrit weekly x 6). The day after the last injection/transfusion, mice were sacrificed and tissues (blood, liver, spleen, and duodenum) and feces, from the cecum and rectum, were collected. Iron levels in tissues and in rectal feces were quantified by a wet ashing procedure. Commercial ELISA kits were used to quantify circulating hepcidin and ferritin levels. DNA from feces was extracted using the Fecal DNA extraction kit (Mo Bio) and sent to the Molecular Research (MRDNA) center for 16S rDNA Illumina platform sequencing and analysis. Statistical analyses were performed using LEfSe database (https://huttenhower.sph.harvard.edu/galaxy/) and GraphPad Prism.RESULTS: Mice fed an iron-deficient diet from weaning developed iron deficiency anemia with decreased intracellular iron stores, as measured by serum ferritin and liver and spleen iron (see Table). Iron dextran injections induced iron overload in mice fed either an iron deficient or iron replete diet. Chronic transfusion induced iron overload in mice fed an iron replete diet, but led to iron repletion without overload in mice fed an iron deficient diet. The iron deficient diet decreased, whereas the iron supplemented diet increased, fecal iron significantly. Although, iron dextran injections and chronic transfusion increased hepcidin levels, they did not significantly affect fecal iron. Analysis of microbiome data showed that fecal iron modulated the relative abundance of different bacteria. The phylum Proteobacteria showed a negative trend with increasing fecal iron associated with decreasing relative abundance (R2 0.5; p<0.006), Firmicutes showed a positive trend with increasing fecal iron associated with increasing relative abundance (R2 0.3; p<0.02), whereas the phylum Bacteroidetes did not show a significant association. Within the phylum Firmicutes, fecal iron concentration was a reasonable predictor of family Lactobacillaceae abundance (R2 0.5; p=0.005), with increasing iron reducing the relative abundance; in contrast, increasing iron was associated with increased relative abundance of family Clostridiaceae (R2 0.7; p<0.0001). We next investigated whether iron dextran infusions, chronic transfusions, or oral iron supplementation modulated microbiome composition. Analysis of the families belonging to class Clostrida showed that family Clostridiaceae increased with an iron supplemented diet, iron dextran infusions, or transfusional iron overload; family Eubacteriaceae increased with iron dextran and blood transfusions, but not with the iron supplemented diet, and family Peptococcaceae only increased with iron dextran treatment. These results suggest that different methods of iron supplementation or overload affect families in the class of Clostrida differently. Finally,comparisons of the cecal and rectal microbiomes did not identify any substantial differences.CONCLUSIONS: In this study, iron status modified the microbiome in mice. The microbiome was further modulated by different types of iron overload, especially in the class Clostrida. Similar to human studies, increasing fecal iron decreases the abundance in the gut of potentially beneficial lactobacilli. Although there are differences between mouse and human gut microbiomes, this mouse model can be used to study the effects of iron supplementation strategies and iron overload and can provide the foundation for further studies focused on the role of iron in host-pathogen interactions and immune function. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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.

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.

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.

Intravenous Iron Dextran as a Component of Anemia Management in Chronic Kidney Disease: A Report of Safety and Efficacy

Objective. We aimed to demonstrate safety and efficacy of intravenous (IV) low molecular weight iron dextran (LMWID) during treatment of anemic stage 3 and 4 chronic kidney disease (CKD) patients. Methods. Efficacy data was obtained by retrospective chart review of 150 consecutively enrolled patients. Patients were assigned per protocol to oral or IV iron, with IV iron given to those with lower iron stores and/or hemoglobin. Iron and darbepoetin were administered to achieve and maintain hemoglobin at 10–12 g/dL. Efficacy endpoints were mean hemoglobin and change in iron indices approximately 30 and 60 days after enrollment. Safety data was obtained by retrospective review of reported adverse drug events (ADEs) following 1699 infusions of LMWID (0.5–1.0 g). Results. Mean hemoglobin, iron saturation, and ferritin increased significantly from baseline to 60 days in patients assigned to LMWID (hemoglobin: 11.3 versus 9.4 g/dL; iron saturation: 24% versus 12.9%; ferritin: 294.7 versus 134.7 ng/mL; all P values < 0.0001). Iron stores and hemoglobin were maintained in the group assigned to oral iron. Of 1699 iron dextran infusions, three ADEs occurred. Conclusions. Treatment of anemia in CKD stages 3 and 4 with LMWID and darbepoetin is efficacious. The serious ADE rate was 0.06% per infusion.

Intravenous Iron Monotherapy for Absolute and Functional Iron Deficiency Anemia in Cancer Patients

AbstractAbstract 5167 ObjectiveIron deficiency anemia (IDA) is common in cancer patients. The Hemoglobin (Hb) response rate in cancer patients with IDA who receive an erythropoiesis stimulating agent (ESA) ranges from 25 – 65% and is increased to 68 – 93% when intravenous (IV) iron is added to the ESA. Interestingly, there have been no studies to date that have evaluated Hb response to IV iron monotherapy for the treatment of IDA in cancer patients. The National Comprehensive Cancer Network (NCCN) recommends treating absolute IDA (AIDA, serum ferritin < 30 ng/mL and TSAT < 15%) with iron monotherapy, preferably IV. However, the NCCN recommends that functional IDA (FIDA, serum ferritin ≤ 800 ng/mL and TSAT < 20%) be treated with both IV iron plus an ESA. Unfortunately, ESAs carry black box warnings for increased mortality, cancer progression, and venous thromboembolism. Therefore, it is important to explore other ways to more safely treat IDA in cancer patients. The objective of this study was to evaluate the Hb response rate to IV iron monotherapy in cancer patients with AIDA and FIDA. MethodsA retrospective chart review was performed at the Huntsman Cancer Institute between January 2006 and June 2011 in cancer patients with AIDA or FIDA who were treated with low molecular weight iron dextran (LMWID) monotherapy. Patients were excluded if they had a ferritin > 800 ng/mL or TSAT ≥ 20%, received an ESA within 6 weeks prior to or within 4 weeks after the LMWID infusion, or received a packed red blood cell transfusion prior to the LMWID infusion without a documented post- transfusion, pre-LMWID infusion Hb. The primary outcome was the proportion of patients with a Hb response defined as an increase of at least 1 g/dL within 6 weeks post IV iron infusion. The secondary outcome was the Hb response within 6 weeks stratified by dose of IV iron. ResultsTwo hundred patients received LMWID at our institution within the specified time period. However, 182 patients were excluded because they did not have active cancer, did not have a definitive diagnosis of AIDA or FIDA, or received concomitant therapy with an ESA. Eighteen patients with either a hematologic or solid malignancy were included. Thirteen patients had AIDA and 5 patients had FIDA. Eight of the 13 (62%) patients in the AIDA group had a Hb response. The median Hb increase in the AIDA group was 1. 3 g/dL (p < 0. 0001). A Hb response was observed in 4 of the 5 (80%) patients in the FIDA group. The median Hb increase in the FIDA group was 1. 8 g/dL (p = 0. 0224). Of the 8 patients with AIDA achieving a response, 4 received less than and 4 received more than the calculated total IV iron dose (equation per package insert). Of the 4 patients achieving a Hb response in the FIDA group, 3 received less than and 1 received equal to the calculated total dose. The overall Hb response rate to IV iron monotherapy for both groups was roughly 67% which is greater than the Hb response rate reported with ESAs alone. See Table 1 for individual patient details. ConclusionAlthough our study has limited patient numbers, this is the first data suggesting that IV iron without an ESA may be an effective treatment for both AIDA and FIDA in anemic patients with a variety of malignancies. IV iron monotherapy may eliminate the need for an ESA. This hypothesis should be tested in larger studies.Table 1:Individual Patient Baseline Demographics and Hb ChangeType of CancerFerritin (ng/mL)TSAT (%)Baseline Hb (g/dL)LMWID dose (gm) infusedCalculated LMWID dose (gm)% of TDI givenHb (g/dL) ≤ 6 weeksHb (g/dL) ChangeAbsolute IDAColorectal1548.821.314512.2+3.4Plasmacytic lymphoma2647.4221008.3+0.9GIST1049.211.56310.5+1.3MM12611.711.46812.3+0.6DLBCL1869.22.2211310.5+1.3MM961211.56811.7-0.3CMML2278.621.216410.9+2.3MM1098.60.823910.4+1.8Inflammatory breast1849.621.315411.3+1.7NSCLC1858.4221009.1+0.7Esophageal1039.611.75812+2.4NSCLC2249.111.85410.9+1.8Colorectal2957.61.12.3478.5+0.9Functional IDACMML4159.51.51.88611.4+1.9Bladder1356101110011.4+1.4Esophageal1981110.111.8579.9-0.2Rectal152199.311.75911.1+1.8MM62159.30.81.94212.7+3.4CMML = chronic myelomonocytic leukemia, DLBCL = diffuse large b-cell lymphoma, GIST = gastrointestinal stromal tumor, Hb = hemoglobin, LMWID = low molecular weight iron dextran, MM = multiple myeloma, NSCLC = non-small cell lung cancer. Disclosures:Off Label Use: The total dose infusion of low molecular weight iron dextran is not an FDA approved dosing regimen. However, it is commonly used in practice and has been used in other studies. Rodgers:American Regent: Consultancy.

Intravenous iron replacement for persistent iron deficiency anemia after Roux-en-Y gastric bypass

BackgroundIron deficiency is a major postoperative complication of Roux-en-Y gastric bypass surgery. Oral replacement can fail to correct the deficiency. Thus, recourse to parenteral iron administration might be necessary. Our objective was to evaluate the effectiveness and safety of a standardized 2 g intravenous iron dextran infusion in the treatment of iron deficiency after Roux-en-Y gastric bypass surgery. The setting was a university-affiliated community hospital in the United States. MethodsWe reviewed the medical records of 23 patients at our institution who had received 2 g of iron dextran intravenously for recalcitrant iron deficiency after Roux-en-Y gastric bypass surgery. We obtained the demographic data and the complete blood count and serum iron studies obtained before treatment and at outpatient visits after infusion. ResultsBefore treatment, all 23 patients were iron deficient (average ferritin 6 ng/mL) and anemic (average hemoglobin 9.4 g/dL). By 3 months, the average ferritin and hemoglobin had increased to 269 ng/mL and 12.3 g/dL, respectively. The hemoglobin levels remained stable throughout the follow-up period. The iron stores were adequately replaced in most patients. Four patients required a repeat infusion by 1 year, because the ferritin levels had decreased to <15 ng/mL. The probability of remaining in an iron replete state was 84.6% (95% confidence interval 78–91.2%). One patient required warm compresses for superficial phlebitis. No other significant adverse events were reported. ConclusionIntravenous administration of 2 g of iron dextran corrects the anemia and repletes the iron stores for ≥1 year in most patients. This therapy is safe, tolerable, efficient, and effective.

Calculation skills for nurses: intravenous iron dextran infusions

T topic of this article in the calculation skills series is calculating doses of intravenous iron dextran infusion (CosmoFer®) for the correction of iron deficiency anaemia. Intravenous iron for the correction of iron deficiency anaemia is indicated in the following scenarios (Vitaline Pharmaceuticals, 2010): n When oral iron replacement therapy is not tolerated or has been proven to be ineffective n Where there is a clinical need to deliver iron rapidly to iron stores. This article is specifically concerned with calculating the dose for a total dose infusion (TDI) of parenteral iron which is an advantage that CosmoFer® (Vitaline Pharmaceuticals, 2010) has over Venofer®, an alternative parenteral iron preparation. When calculating a TDI infusion, the Ganzoni formula is used to calculate the dose of CosmoFer® to be infused:

Traitement de la carence martiale par injection d’une dose totale de fer dextran en dialyse péritonéale

Introduction The main objective of this study is to determine whether a single dose of iron dextran can correct iron deficiency during a period of four months in peritoneal dialysis patients. Method This was a prospective observational study in peritoneal dialysis patients who had anemia (hemoglobin <11 g/dL) and iron deficiency (ferritin <100 μg/L and/or transferrin saturation < 20%). Patients who were resistant to oral iron or who could not tolerate oral iron were included in the study. At baseline, based on the iron deficiency estimation, a single dose of iron dextran was infused over four hours. Results Of 17 patients included, 12 completed the study. The mean iron dose infused was 742 ± 150 mg. No clinically significant adverse event was reported during the infusion. Four months after the iron dextran infusion there was a significant increase of the mean hemoglobin level (10.1 ± 0.7 g/dl vs 11.4 ± 1.2 g/dL, P < 0.05), the mean blood ferritin level (66 ± 46 mg/L vs 212 ± 121 mg/L, P < 0.05) and the mean transferrin saturation (14 ± 5% vs 23 ± 8, P < 0.05). Four months after the iron infusion 10 patients had a blood ferritin level higher than 100 μg/L and a transferrin saturation higher than 20%. There was no significant modification of the erythropoietin dose during the four months period. Conclusion In patients treated by peritoneal dialysis, the anemia due to iron deficiency can be treated by a single infusion of iron dextran for a period of four months.

Accelerated total dose infusion of low molecular weight iron dextran is safe and efficacious in chronic kidney disease patients

Low molecular weight iron dextran (LMWID) is licensed for use as a total dose infusion (TDI) over 4-6 h. In order to improve patient convenience and cost-effectiveness of therapy, we investigated the safety and efficacy of adopting accelerated dosing regimens and compared this with a standard rate LMWID infusion. A retrospective study of patients undergoing accelerated and standard rate TDI of LMWID was conducted across three centres. A total of 1904 doses of LMWID were administered at an accelerated rate of 1 g over 1 h 40 min. This was compared with 395 patients who had standard rate infusion of 1 g LMWID over 3-4 h. There were eight minor adverse events in patients receiving accelerated dose LMWID (8/1904, 0.42%) in comparison to one adverse event in patients receiving a standard regimen (1/395, 0.25%). No serious adverse events occurred. Serum haemoglobin and ferritin significantly improved in both groups. TDI LMWID is a safe and efficacious method of iron replacement. Accelerated infusion regimen is safe and compares well with standard rate infusion regimen. Furthermore, accelerated TDI of LMWID enables greater numbers of patients to be treated and consequently there appear to be advantages for both patient and health resources.