Use Of Intravenous Iron Research Articles

P592 Costs savings associated with ferric maltol and the reduced use of intravenous iron based on real world data

Abstract Background Intravenous (IV) iron is frequently used in patients with iron deficiency (ID) when conventional oral ferrous products are ineffective or cannot be used (e.g. due to poor tolerability). Oral ferric maltol is a new iron ferric product registered in Europe and US. The aim of this study was to quantify the use of IV iron before and after the introduction of the new oral ferric maltol in real world settings and extrapolate the overall costs involved. Methods Data were collected from a single centre German clinical practice, MVZ für Immunologie, in inflammatory bowel disease (IBD) patients treated with iron therapy for ID with or without anaemia between 2013 and 2019 through the systematic CEDUR IBD registry and local medical records. The first cohort was formed of patients treated between 2013 and 2015, receiving only IV iron as ferric carboxymaltose (FCM). The second cohort was formed of patients treated between 2017 and 2019, receiving either oral ferric maltol only or ferric maltol in combination with FCM. Costs involved in each cohort were extrapolated using a societal perspective. Results Following the introduction of oral ferric maltol, the actual total number of FCM infusions observed was 138, showing a decrease of 70% compared to the first cohort in which oral ferric maltol was not available. This decreased number of infusions between the two cohorts was associated with total costs-savings of €56,933. In the first cohort, the administration costs were €44,536, the drug acquisition costs were €59,536 and the productivity loss were €30,944. In the second cohort, the administration costs were €13,597 the drug acquisition costs were €55,028 and the productivity loss were €9,447. A secondary scenario strictly applying the doses taken from respective SmPCs was tested and resulted in greater costs-savings. Noteworthy, the mean (SD) haemoglobin (Hb) level at baseline in the first cohort was lower with 11.5g/dl (1.19) vs. 12.2g/dl (1.18) in the second cohort. Three to six months after the treatment had been stopped, the mean (SD) Hb level was 13g/dl in both the first and second cohort with a SD of 1.31 and 1.37 respectively, showing that Hb levels were maintained in both cohorts. Conclusion The introduction of the new oral ferric maltol resulted in a decrease of 70% in terms of number of FCM infusions which was associated with costs-savings of €56,933 in terms of administration, drug acquisition and productivity loss costs. Considering that Hb levels were maintained in both cohorts, these results indicate that ID patients with or without anaemia previously treated with IV iron can also be managed effectively with oral ferric maltol resulting in overall societal cost-savings.

Innovative Technology – Enhancing Healthcare for All (Vol. 25, No. 5, Full Issue)

For the month of May 2021, APBN discovers how the used of digital technology and innovative new methods can help treatment, prevention and management of diseases. In the Columns section, we have a contribution by Son Pham, Country Manager for GE Healthcare Vietnam and the CEO for GE Vietnam on how technology has helped healthcare systems in Vietnam during the COVID-19 pandemic. In the Spotlights section, read about a research study by the National Heart Centre Singapore (NHCS) and its international partners affirm the use of intravenous iron to help heart failure patients improve health outcomes.

POS-283 HEMOGLOBIN (HB) CORRECTION WITH ROXADUSTAT IS ASSOCIATED WITH IMPROVED IRON HOMEOSTASIS IN PATIENTS WITH NON-DIALYSIS-DEPENDENT (NDD) AND DIALYSIS-DEPENDENT (DD) CHRONIC KIDNEY DISEASE (CKD)

Anemia in CKD is caused largely by reduced erythropoietin production, decreased bone marrow responsiveness to erythropoietin, and hepcidin-induced functional iron deficiency. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases Hb by stimulating erythropoietin synthesis, increasing bone marrow responsiveness to erythropoietin, and improving iron availability. Roxadustat also decreases hepcidin and increases the expression of genes involved in iron mobility. In this post hoc analysis, we assessed the effect of treatment with roxadustat on iron parameters in patients with NDD-CKD and DD-CKD. Patients were randomized to double-blind roxadustat or placebo in three pivotal Phase 3 NDD-CKD trials (OLYMPUS, ALPS, and ANDES) and randomized to open label roxadustat or epoetin alfa in three pivotal Phase 3 DD-CKD trials (ROCKIES, SIERRAS, and HIMALAYAS). In patients with NDD-CKD, oral iron was administered without restriction per discretion of the treating physician; intravenous (IV) iron use was limited to rescue therapy. In patients with DD-CKD, IV iron was administered per usual care in the epoetin alfa group and was restricted in the roxadustat group; oral iron was not restricted in either group. Mean changes from baseline (BL) in Hb, IV iron dose, hepcidin, and iron parameters were evaluated. Pooled results per patient population are reported. Overall, 4277 patients with NDD-CKD (roxadustat N=2391; placebo N=1886; mean BL Hb 9.1 g/dL for both groups) and 3890 patients with DD-CKD (roxadustat N=1943; epoetin alfa N=1947; mean BL Hb 9.6 g/dL for roxadustat and 9.7 g/dL for epoetin alfa), including 1530 incident dialysis patients, were evaluated. In patients with NDD-CKD, mean change in Hb from BL to Weeks 28–52 was greater with roxadustat than placebo (1.9 vs 0.2 g/dL; P<0.0001). Fewer roxadustat-treated patients required IV iron than placebo-treated patients up to Week 52 (2.6% vs 6.0%; P<0.0001). Treatment with roxadustat reduced ferritin and resulted in modest reductions in transferrin saturation (TSAT) vs placebo. Roxadustat treatment increased serum iron and total iron-binding capacity (TIBC), and reduced hepcidin compared with placebo (Figure 1). In patients with DD-CKD, mean Hb increased more from BL to Weeks 28–52 with roxadustat vs epoetin alfa (1.21 vs 0.95 g/dL; P<0.0001). Roxadustat-treated patients used less monthly IV iron compared with epoetin-alfa treated patients over Weeks 28–52 (52.2 vs 66.8 mg; P<0.0001). Roxadustat reduced ferritin compared with epoetin alfa. While no changes were seen in TSAT, roxadustat increased serum iron and TIBC, and reduced hepcidin compared with epoetin alfa (Figure 2). View Large Image Figure ViewerDownload Hi-res image Download (PPT) In both patients with NDD-CKD and DD-CKD, roxadustat facilitated iron transport and utilization resulting in increases in both serum iron and TIBC, likely driven by reduced hepcidin. Overall, despite the observed greater Hb increase from BL with roxadustat, IV iron use was reduced with roxadustat in both the NDD-CKD and DD-CKD populations.

Using iron-based phosphate binders in phosphate reduction and anemia improvement in patients receiving dialysis: a meta-analysis of randomized controlled trials.

A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis. For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients. Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments. FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality.

Preoperative intravenous iron for anaemia in elective major open abdominal surgery: the PREVENTT RCT.

Anaemia affects 30-50% of patients before they undergo major surgery. Preoperative anaemia is associated with increased need for blood transfusion, postoperative complications and worse patient outcomes after surgery. International guidelines support the use of intravenous iron to correct anaemia in patients before surgery. However, the use of preoperative intravenous iron for patient benefit has not been assessed in the setting of a formal clinical trial. To assess if intravenous iron given to patients with anaemia before major abdominal surgery is beneficial by reducing transfusion rates, postoperative complications, hospital stay and re-admission to hospital, and improving quality of life outcomes. A multicentre, double-blinded, randomised, controlled, Phase III clinical trial, with 1 : 1 randomisation comparing placebo (normal saline) with intravenous iron (intravenous ferric carboxymaltose 1000 mg). Randomisation and treatment allocation were by a secure web-based service. The study was conducted across 46 hospitals in England, Scotland and Wales between September 2013 and September 2018. Patients aged > 18 years, undergoing elective major open abdominal surgery, with anaemia [Hb level of > 90 g/l and < 120 g/l (female patients) and < 130 g/l (male patients)] who could undergo randomisation and treatment 10-42 days before their operation. Double-blinded study comparing placebo of normal saline with 1000 mg of ferric carboxymaltose administered 10-42 days prior to surgery. Co-primary end points were risk of blood transfusion or death at 30 days postoperatively, and rate of blood transfusions at 30 days post operation. A total of 487 patients were randomised (243 given placebo and 244 given intravenous iron), of whom 474 completed the trial and provided data for the analysis of the co-primary end points. The use of intravenous iron increased preoperative Hb levels (mean difference 4.7 g/l, 95% confidence interval 2.7 to 6.8 g/l; p < 0.0001), but had no effect compared with placebo on risk of blood transfusion or death (risk ratio 1.03, 95% confidence interval 0.78 to 1.37; p = 0.84; absolute risk difference +0.8%, 95% confidence interval -7.3% to 9.0%), or rates of blood transfusion (rate ratio 0.98, 95% confidence interval 0.68 to 1.43; p = 0.93; absolute rate difference 0.00, 95% confidence interval -0.14 to 0.15). There was no difference in postoperative complications or hospital stay. The intravenous iron group had higher Hb levels at the 8-week follow-up (difference in mean 10.7 g/l, 95% confidence interval 7.8 to 13.7 g/l; p < 0.0001). There were a total of 71 re-admissions to hospital for postoperative complications in the placebo group, compared with 38 re-admissions in the intravenous iron group (rate ratio 0.54, 95% confidence interval 0.34 to 0.85; p = 0.009). There were no differences between the groups in terms of mortality (two per group at 30 days post operation) or in any of the prespecified safety end points or serious adverse events. In patients with anaemia prior to elective major abdominal surgery, there was no benefit from giving intravenous iron before the operation. The impact of iron repletion on recovery from postoperative anaemia, and the association with reduced re-admission to hospital for complications, should be investigated. In the preoperative intravenous iron to treat anaemia in major surgery (PREVENTT) trial, all patients included had anaemia and only 20% had their anaemia corrected before surgery. The definition and causality of iron deficiency in this setting is not clear. Current Controlled Trials ISRCTN67322816 and ClinicalTrials.gov NCT01692418. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25 No. 11. See the NIHR Journals Library website for further project information.

Interventions for treating iron deficiency anaemia in inflammatory bowel disease.

Interventions for treating iron deficiency anaemia in inflammatory bowel disease.

Red Blood Cell Transfusion and the Use of Intravenous Iron in Iron Deficient Patients Presenting to the Emergency Department

Background: Red blood cell (RBC) transfusions are often used to treat patients with iron deficiency who present to the emergency department (ED) with symptomatic anemia. Intravenous (IV) iron is the preferred treatment in this setting, as it has been shown to increase hemoglobin concentration rapidly and durably. We aim to determine the incidence of iron deficiency anemia (IDA) and the management of these patients in the ED setting. Objectives: To evaluate the incidence of IDA, the frequency of RBC transfusion and iron supplementation, and factors associated with RBC transfusion. Study Design: Retrospective cohort study of all adult patients presenting to the St Boniface Hospital (Winnipeg, CAN) ED from January 2014 to January 2019. Methods: We used electronic data from the Emergency Department Information System (EDIS) and Laboratory Information Services (LIS) databases to identify patients presenting with IDA, defined as anemia (hemoglobin &amp;lt;120 g/L) with either a transferrin saturation less than 20% or ferritin less than 30 umol/L, or mean corpuscular volume (MCV) of &amp;lt; 75 fL. A ferritin greater than 100 umol was used to exclude IDA, regardless of MCV. We extracted patient demographics, diagnoses, markers of iron storage, RBC transfusion and use of IV iron. Multivariate logistic regression analysis was used to evaluate factors associated with RBC transfusion. Results: Of 39222 patients, 17945 (45%) were anemic. Of the anemic patients, iron parameters were ordered in 1848 (10.3%) patients, and IDA was present in 910 (5.1 %). In the IDA population, 95 patients (10.4 %) received 1 RBC unit, and 197 patients (21.6 %) received 2 or more units. Oral iron and IV iron were prescribed for 64 (7 %) and 14 (1.5 %) patients, respectively. Our logistic regression model demonstrated that hemoglobin concentration was the main determinant of whether patients received RBC transfusion. Other variables including patient age, cardiac symptoms, heart rate, blood pressure, and CTAS score were not associated with increased likelihood of receiving RBC transfusion. Conclusion: Iron parameters were infrequently ordered in the evaluation of anemia in the ED, with limited use of oral and IV iron. The decision to transfuse RBCs was primarily influenced by hemoglobin concentration, but not other surrogates of hemodynamic instability. An interventional study to improve education and access to oral and IV iron is planned to reduce unnecessary RBC transfusions and their associated risks in patients with IDA. Disclosures No relevant conflicts of interest to declare.

The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians

BackgroundIron deficiency anaemia in pregnancy (IDAP) affects 11–18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP.MethodsAn online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing.ResultsOf 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed.ConclusionsAlmost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.

Incidence of Iron Deficiency and the Role of Intravenous Iron Use in Perioperative Periods.

Iron deficiency is a major problem in worldwide populations, being more alarming in surgical patients. In the presence of absolute iron deficiency (depletion of body iron), functional iron deficiency (during intense bone marrow stimulation by endogenous or exogenous factors), or iron sequestration (acute or chronic inflammatory conditions), iron-restricted erythropoiesis can develop. This systemic review was conducted to draw attention to the delicate problem of perioperative anemia, and to provide solutions to optimize the management of anemic surgical patients. Systemic reviews and meta-analyses, clinical studies and trials, case reports and international guidelines were studied, from a database of 50 articles. Bone marrow biopsy, serum ferritin levels, transferrin saturation, the mean corpuscular volume, and mean corpuscular hemoglobin concentration were used in the diagnosis of iron deficiency. There are various intravenous iron formulations, with different pharmacological profiles used for restoring iron. In surgical patients, anemia is an independent risk factor for morbidity and mortality. Therefore, anemia correction should be rapid, with parenteral iron formulations—the oral ones—being inefficient. Various studies showed the safety and efficacy of parenteral iron formulations in correcting hemoglobin levels and decreasing the blood transfusion rate, the overall mortality, the postoperative infections incidence, hospitalization days, and the general costs.

Administration of intravenous iron and tranexamic acid in the management of postoperative iron deficiency anaemia following free flap reconstruction: re-audit

Following free tissue transfer, intravenous iron (IVI) has a role in reducing the rates of blood transfusion and more rapidly restoring haemoglobin (Hb) levels. Anaemia has a detrimental effect on survival, postoperative complications, fatigue, and health-related quality of life, therefore early correction is recommended. The aim of this re-audit is to assess the use of IVI, of tranexamic acid intraoperatively, and of perioperative blood transfusions. A total of 148 consecutive patients who underwent ablative surgery and free flap reconstruction between May 2018 and September 2019 were audited. The median (IQR) age was 66 (59,72) years and 36% were female. For two-thirds, surgery was for cancer located in the oral cavity and two-thirds of the free flaps were soft tissue. Tranexamic acid (TXA) was used intraoperatively for 30%, red blood cells (RBC) were transfused for 20% and 55 patients (37%) received IV iron. This compares with 4%, 26%, and 0, respectively, in the initial audit. Those having IVI were more likely (56%) to have had a composite flap, a lower postoperative haemoglobin and lower discharge Hb. The Hb between four and twelve weeks’ follow up, known for 40, was a median (IQR) of 122 (104,138). There were no adverse reactions to IV iron. Although it is straightforward to administer IVI postoperatively, this re-audit demonstrates that it can be a challenge to embed change in protocols. Through raised awareness of the benefits of IVI, lack of adverse events and clarification of selection criteria, it is hoped that rates of IVI use will increase.

Iron deficiency and iron therapy in heart failure and chronic kidney disease.

Iron deficiency is common and associated with adverse outcomes in heart failure, regardless of anemia. Iron deficiency, absolute and functional, with and without anemia, is associated with adverse outcomes in chronic kidney disease (CKD). Heart failure and CKD frequently occur together. Intravenous iron therapy has been shown to reduce heart failure symptoms and improve physical function in heart failure with reduced ejection fraction with iron deficiency. In CKD, intravenous or oral iron therapy are often used for management of anemia, along with erythropoiesis stimulating agents, yet the risks and benefits of intravenous iron use is controversial. In this review, we survey available evidence and ongoing studies of iron deficiency and iron supplementation in heart failure, and integrate with recent evidence on effectiveness and safety of intravenous iron therapy in CKD. Intravenous iron therapy improves heart failure symptoms and physical function in heart failure with reduced ejection fraction and iron deficiency, regardless of anemia, and may reduce heart failure hospitalizations and cardiovascular mortality. Sustained intravenous iron therapy regardless of hemoglobin level in selected patients with end-stage kidney disease receiving hemodialysis improves outcomes, and does not appear to cause infectious complications. Iron therapy has important effects in heart failure and CKD, and appears safe in the short term. Ongoing trials will provide additional important information.

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) &amp;lt; 200microg/L and/or transferrin saturation (TS) &amp;lt;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 &amp;lt;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 &amp;lt;0.001) and IS (21.1% to 91.4%; p-value&amp;lt;0.01) to values &amp;gt;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.

A retrospective analysis of venous thromboembolism trends in chemotherapy-induced anemia: Red blood cell transfusion versus erythrocyte stimulating agent administration.

BackgroundPatients receiving a variety of chemotherapy regimens often develop chemotherapy‐induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs.MethodsA retrospective study analyzed 10,269 University of Pennsylvania Health System patients with malignancies of various type, stage, and histopathology who developed CIA between 2008 and 2017. Using multivariate Cox regression, we determined adjusted hazard ratios (and corresponding 95% confidence intervals) of VTE development after adjusting for RBC and ESA intervention (all during the 90 days following CIA diagnosis).ResultsAmong the 10,269 patients with CIA, 2,642 (25.7%) developed a VTE within the 90‐day period. VTE risk following RBC transfusion (HR = 1.37, 95% CI 1.24‐1.50, P < .001) was more than twice as common as VTE risk following ESA administration (HR = 0.53, 95% CI 0.40‐0.69, P < .001).ConclusionWhile both RBC transfusion and ESA are independently associated with VTE, our data suggest a greater risk of VTE development with RBC transfusion as compared with ESA.

Use of intravenous iron in patients with iron deficiency and chronic heart failure: Real-world evidence

Introduction and objectivesTreatment with intravenous iron in patients with heart failure (HF) and iron deficiency (ID) improves symptoms, however its impact on survival and safety is unknown. We aimed to evaluate the management of ID and anemia with intravenous iron in patients with HF and long-term safety of intravenous iron. MethodsWe evaluated anemia and ID in patients with chronic HF at 3 university hospitals. Anemia was defined using the World Health Organization definition and ID was defined as ferritin <100 ug/L or a Transferrin Saturation <20% if ferritin between 100 and 299 ug/L. We assessed treatment with intravenous iron during follow-up and its association with mortality and HF hospitalizations using multivariate cox regression analysis. ResultsWe included 2,114 patients, median age 72 years and 57% had reduced left ventricular ejection fraction. ID was present in 55% and ID and anemia in 29%. Treatment with intravenous iron was used in 24% of patients with ID and 34% of patients with ID and anemia. In patients with ID, after multivariate adjustment, treatment with intravenous iron was associated with lower all-cause mortality: HR = 0.38 (0.28–0.56), lower cardiovascular mortality: HR = 0.34 (0.20–0.57) and no differences in HF hospitalizations: HR = 1.15 (0.88–1.50). Similar outcomes were found for patients with anemia and ID. ConclusionsIn a real-world cohort of patients with HF, treatment with intravenous iron was used in one third of patients with ID and anemia and appears safe in mid-term follow-up.

Hypophosphatemia Associated with Intravenous Iron Therapies for Iron Deficiency Anemia: A Systematic Literature Review.

BackgroundIron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia.ObjectiveThe purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US).MethodsA systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs.ResultsThe SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as “asymptomatic” or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities.ConclusionStudies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

Use of intravenous iron therapy in colorectal cancer patient with iron deficiency anemia: a propensity-score matched study.

Iron deficiency anemia is common in colorectal cancer patients and is related to poor surgical outcome. Increasing evidence supports preoperative use of intravenous iron (IVI) to correct anemia. Our study investigates effect of preoperative IVI on hemoglobin level. From August 2017 to March 2019, colorectal cancer patients with iron deficiency anemia received intravenous iron at least 2weeks before their scheduled operations (IVI group). These patients' prospectively collected data were compared to a historic cohort of anemic patients who received elective colorectal surgery within 3years before the study period (non-IVI). Forty-six patients were included after receiving intravenous iron. After propensity score matching on 1:2 ratio, 38 patients in IVI group were matched with 62 patients from non-IVI group. There was no statistical difference for preoperative mean hemoglobin level between the two groups (8.43g/dL in IVI, 8.79g/dL in non-IVI, p = 0.117), but IVI group has significantly higher mean hemoglobin level on admission (10.63g/dL in IVI, 9.46g/dL in non-IVI, p = < 0.001). IVI group had higher median hemoglobin rise (1.9 in IVI, 0.6 in non-IVI, p = <0.001) and significantly less red cell transfusion (8 patients in IVI, 30 in non-IVI, p = 0.006). Subgroup analysis showed that less patients in IVI group required transfusions in preoperative period (1 in IVI group, 20 in non-IVI, p < 0.001). Our data suggested that IVI can significantly increase hemoglobin level in iron deficiency anemic patients before colorectal surgery, with reduction in red cell transfusions.

Perioperative iron deficiency anemia in obstetrics. Possibilities of prevention and correction. Review

In the review diagnostics and correction of iron deficiency anemia (IDA) is considered during pregnancy and in the perioperative period within the concept of “patient blood management”. Features of diagnosis of anemia and verification of an iron deficiency (ID) are discussed during pregnancy, correction stages with use of oral and intravenous iron, transfusion erythrocytes and reinfusion of blood. Data on advantage of intravenous iron to correction of ID and IDA are provided during pregnancy and in the perioperative period.

The role of iron repletion in adult iron deficiency anemia and other diseases.

Iron deficiency anemia (IDA) is the most prevalent and treatable form of anemia worldwide. The clinical management of patients with IDA requires a comprehensive understanding of the many etiologies that can lead to iron deficiency including pregnancy, blood loss, renal disease, heavy menstrual bleeding, inflammatory bowel disease, bariatric surgery, or extremely rare genetic disorders. The treatment landscape for many causes of IDA is currently shifting toward more abundant use of intravenous (IV) iron due to its effectiveness and improved formulations that decrease the likelihood of adverse effects. IV iron has found applications beyond treatment of IDA, and there is accruing data about its efficacy in patients with heart failure, restless leg syndrome, fatigue, and prevention of acute mountain sickness. This review provides a framework to diagnose, manage, and treat patients presenting with IDA and discusses other conditions that benefit from iron supplementation.

Evaluation of the Relationship Between Advanced Oxidation end Products and Inflammatory Markers in Maintenance Hemodialysis Patients

Introduction Increased oxidative stress and blunted anti-oxidant mechanisms are important problems in hemodialysis (HD) patients. Reactive oxygen species (ROS) act directly on proteins, leading to the formation of oxidized amino acids. Advanced oxidation protein products (AOPP) are among these substances. Many oxidant substances increase the level of AOPP. Iron is an element with strong oxidant capacity, especially when used intravenously. It is thought that iron treatment further increases the oxidative stress in HD patients. We aimed to investigate the relationship between AOPP and inflammatory status in HD patients. Materials and Methods Patients who were on maintenance HD program without additional co-morbidities and no history of use of intravenous iron within the last two weeks were recruited in the study. The blood samples taken just before the dialysis session were analyzed for AOPP, serum iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), ß2-microglobulin, fibrinogen, interleukin (IL)-1, IL-6 and tumor necrosis factor-α levels besides routine biochemical measurements and complete blood count. Results The number of patients included in the study was 102 (n: 53 female, %52.0) and the mean age was 47.6±13.9 years. The mean transferrin saturation was 25.4%. AOPP levels, iron use in patients was higher compared to patients who do not use (respectively 2.58±0.19 mmol/l and 2.50 ±0.16mmol/l, p = 0.046). We did not detect statistically significant correlation of AOPP levels with iron parameters and other inflammatory markers. Conclusion The present study showed that intravenous iron therapy does not increase oxidative stress. Although serum AOPP level was higher in patients on intravenous iron treatment, it was not correlated with iron indices and inflammatory markers. So, intravenous iron may exert its oxidant effect free from serum iron indices.

Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation

Rationale & ObjectivePatients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism.Study DesignProspective single-arm study.Setting & Participants20 individuals with incident kidney failure initiating hemodialysis.ExposureInitiation of hemodialysis. Dose adjustments of phosphate binders and vitamin D receptor activators and use of calcimimetics, erythropoiesis-stimulating agents, and intravenous iron were prohibited.OutcomesChanges in serum levels of FGF-23, soluble Klotho, and other biochemical parameters of mineral metabolism, measured before and after each hemodialysis session, for a total of 4 sessions over 5 days.Analytical ApproachRepeated-measures analysis of variance.ResultsAt baseline, participants had 18-fold higher median FGF-23 levels and 1.6-fold lower mean soluble Klotho levels compared with age- and sex-matched healthy individuals. Initiation of hemodialysis led to progressive reductions in serum phosphorus, intact parathyroid hormone, and FGF-23 levels, with dialysis-related fluctuations. No reductions were observed in levels of α1-microglobulin, which has molecular weight comparable to FGF-23. The magnitude of the FGF-23 level reductions was strongly associated with concomitant changes in serum phosphorus levels but not with the changes in intact parathyroid hormone levels. Soluble Klotho levels did not change after the initiation of hemodialysis.LimitationsSingle-arm design, small sample size, short follow-up period.ConclusionsInitiation of hemodialysis in patients with chronic kidney failure led to progressive reductions in FGF-23 levels in association with reductions in serum phosphorus levels. These results suggest that phosphorus is a strong inducer of FGF-23 production and that regulation of FGF-23 production is a rapid process.