SAT-195 INCREASING USE OF IV IRON FOR PATIENTS ON HEMODIALYSIS RESULTS IN REDUCTION IN ERYTHROPOIETIN DOSE WHILE MAINTAINING TARGET HAEMOGLOBIN

Abstract Background Large randomized clinical trials have demonstrated that intravenous (IV) iron therapy in iron-deficient patients with heart failure with reduced ejection fraction (HFrEF) brings clinical benefits related to symptoms of the disease and exercise capacity. Mechanisms underlying beneficial effects of such repletion are still the subject of interest as this is not solely related to improved haematopoiesis (IV iron works also in non-anaemic subjects). In patients with chronic heart failure iron deficiency (ID) is linked with inflammatory processess but data regarding the impact of IV iron on inflammation is scarce. Purposes We evaluated whether IV iron therapy affects circulating biomarkers of pro-inflammatory state in men with HFrEF and concomitant ID. Methods This is the sub-analysis of the study to investigate the effects of IV ferric carboxymaltose (FCM) on the functioning of skeletal muscles in men with HFrEF. For the purposes of current research we analyzed data of 20 men with HFrEF (median age 68 (62, 75 – in brackets interquartile ranges, respectively) years, LVEF: 30 (25, 35) %, ischaemic HF aetiology: 85%, NYHA class I/II/III: 30%/50%/20%) and ID (definition according to ESC guidelines - ferritin <100 ng/mL, or ferritin 100–299 ng/mL with transferrin saturation [TSAT] <20%) who were randomized in a 1:1 ratio to receive either the 24-week therapy with IV FCM (dosing scheme as in the CONFIRM-HF trial) or saline (controls). The study was double-blinded. We used ELISA to evaluate different circulating pro-inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β], interleukin 22 [IL-22]) at baseline and week 24. Results IV FCM therapy repleted iron stores in men with HFrEF as reflected by an increase in serum ferritin and TSAT, which was not seen in a control group. IV FCM therapy (as well as the saline administration) affected neither haemoglobin concentration nor parameters reflecting iron stores in red cells. Baseline serum ferritin was not related to hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 (all p>0.23). Baseline TSAT was related to hs-CRP (r=−0.47, p=0.02) but not other inflammatory biomarkers. Levels of hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 at week 0 were similar in subjects who received IV iron and controls (all p>0.22). Change from week 0 to week 24 adjusted for baseline value (delta W24-W0 as the percentage of W0) regarding IL-22 was lower in an active treatment arm as compared with saline (p=0.049) and there was a trend towards lower delta TNF-α in FCM group compared to saline (p=0.067). These findings were not valid for other measured pro-inflammatory biomarkers. Conclusions In men with HFrEF and concomitant ID intravenous iron therapy with FCM affects biomarkers of pro-inflammatory state. Clinical relevance of this finding requires further translational research. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This research was funded by the National Science Centre (Poland) grant allocated on the basis of the decision number DEC-2012/05/E/NZ5/00590

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Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial

BMC Oral Health ◽

10.1186/s12903-020-01359-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Min Suk Chae ◽

Mihyun Lee ◽

Min Ho Choi ◽

Je Uk Park ◽

Misun Park ◽

...

Keyword(s):

Blood Transfusion ◽

Blood Group ◽

Whole Blood ◽

Orthognathic Surgery ◽

Hemoglobin Level ◽

Iron Therapy ◽

Iron Group ◽

Autologous Whole Blood ◽

Bimaxillary Orthognathic Surgery ◽

Iv Iron

Abstract Background Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery. Methods This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL. Results Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group. Conclusion As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery. Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2&ltype=my&rtype=my.

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Safety and efficacy of a single total dose infusion (1020 mg) of ferumoxytol

Therapeutic Advances in Hematology ◽

10.1177/20406207211006022 ◽

2021 ◽

Vol 12 ◽

pp. 204062072110060

Author(s):

Harris Khan ◽

Paige May ◽

Elim Kuo ◽

Preetika Pai ◽

Katherine Boles ◽

...

Keyword(s):

Single Dose ◽

Total Dose ◽

Treatment Option ◽

Deficiency Anemia ◽

Utilization Review ◽

Veterans Health ◽

Significant Difference ◽

Dose Infusion ◽

Iv Iron ◽

The Impact

Purpose: Iron deficiency anemia (IDA) is the most common type of anemia. A single dose infusion of intravenous (IV) iron is a convenient treatment option. Ferumoxytol is an IV formulation of iron that is typically given in two doses of 510 mg each. Utilizing a single dose of 1020 mg over 15 min has previously been described as safe and effective. In July 2018, we began to administer a single 1020 mg dose of ferumoxytol to patients needing IV iron replacement at the North Florida/South Georgia Veterans Health System. To evaluate the impact of this change, a utilization review was conducted. Methods: Outcomes of all patients who received ferumoxytol injections in the 6 months prior to and after the dosing strategy change were analyzed. A total of 140 patients, who received 270 separate IV ferumoxytol infusions, were included in the analysis. Results: No significant difference in safety was observed, with one infusion reaction occurring in each group ( p = 1.00). Efficacy also appeared equivalent with no significant difference between the change in hemoglobin for those who received a single 1020 mg dose versus those who received two 510 mg doses ( p = 0.764). As expected, those who received a single total dose infusion of 1020 mg had less clinic utilization ( p < 0.0001). Conclusion: In summary, ferumoxytol administered as a 1020 mg single dose infusion was more convenient and should be considered a safe and effective treatment option for IDA.

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

American Journal of Perinatology ◽

10.1055/s-0041-1740003 ◽

2021 ◽

Author(s):

Adam K. Lewkowitz ◽

Molly J. Stout ◽

Emily Cooke ◽

Seon C. Deoni ◽

Viren D'Sa ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Adverse Reactions ◽

Controlled Trial ◽

Oral Iron ◽

Deficiency Anemia ◽

Randomized Controlled ◽

Iv Iron ◽

Severe Adverse Reactions

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

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Hematologic Abnormalities in Chronic Kidney Disease

10.2310/nephro.1370 ◽

2018 ◽

Author(s):

Michael Auerbach ◽

John Anderson ◽

Khalid Al Talib

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Infusion Reaction ◽

Nonvalvular Atrial Fibrillation ◽

Novel Oral Anticoagulant ◽

Before And After ◽

Iv Iron ◽

A Minor

The focus of this review is on information practical to the practicing nephrologist and internists managing patients with chronic kidney disease (CKD), with an emphasis on the quantitative aspects of risk, diagnosis, treatment, and prognosis. Consequently, anemia associated with non–dialysis-associated CKD is emphasized, with special attention to the role of erythropoiesis-stimulating agents and intravenous (IV) iron in treating the anemia of CKD, as well as sections on uremic bleeding and anticoagulation in CKD patients. Figures show a patient before and after a minor infusion reaction, an algorithm outlining grading and management of acute hypersensitivity reactions to IV iron infusions, and an algorithm for the management of uremic platelet dysfunction. Tables list Food and Drug Administration-recommended dose adjustments for novel oral anticoagulant (NOACs) in CKD patients, evidence for preprocedural withholding of NOACs, and management guidelines for anticoagulation in nonvalvular atrial fibrillation and venous thromboembolism. This review contains 2 highly rendered figures, 3 tables, and 101 references. Key words: Chronic kidney disease; CKD; Anemia of chronic kidney disease; Anemia of CKD; Uremic bleeding; Anticoagulation in CKD; Novel oral anticoagulants in CKD; NOAC CKD

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Target Hemoglobin May Be Achieved with Intravenous Iron Alone in Anemic Patients with Cardiorenal Syndrome: An Observational Study

Cardiorenal Medicine ◽

10.1159/000433564 ◽

2015 ◽

Vol 5 (4) ◽

pp. 246-253 ◽

Cited By ~ 2

Author(s):

Eyal Ben-Assa ◽

Yacov Shacham ◽

Moshe Shashar ◽

Eran Leshem-Rubinow ◽

Amir Gal-Oz ◽

...

Keyword(s):

Platelet Count ◽

Adverse Effects ◽

Observational Study ◽

Treatment Strategy ◽

Intravenous Iron ◽

Cardiorenal Syndrome ◽

Combination Group ◽

Iron Treatment ◽

Significant Difference ◽

Iv Iron

Background: The treatment of anemia in patients with cardiorenal syndrome (CRS) is based mainly on intravenous (IV) iron therapy and/or erythropoiesis-stimulating agents (ESAs). There are concerns about the safety of ESAs due to a potentially higher risk for stroke and malignancy. Objective: We aimed to explore whether IV iron alone is sufficient to improve anemia in CRS patients and to define the predictors of treatment response. Methods: We retrospectively analyzed data of 81 CRS patient treated for anemia at our clinic. All patients received IV iron for 6 weeks. A subset of patients was additionally given subcutaneous ESAs. The end point was the improvement from baseline in hemoglobin (Hb) and ferritin levels at week 7. Results: We retrieved the files of 81 patients; 34 received IV iron alone and 47 were given IV iron and ESAs (the combination group). The Hb levels significantly increased in both groups (in the IV iron alone group: 10.6 ± 1.1 to 11.9 ±1.1 g/dl, p < 0.001; in the combination group: 10.2 ± 0.9 to 12.4 ± 1.3 g/dl, p < 0.001), but more pronouncedly in the combination group (2.17 vs. 1.24 g/dl; p = 0.001). The platelet count decreased significantly in the IV iron alone group but was unchanged in the combination group. Eighty percent of patients attained a Hb target of 11 g/dl, with no significant difference between the two groups (73.5 vs. 85.1%; p = 0.197). Low baseline Hb was the only predictor of a favorable outcome to treatment. Conclusion: Our observational study suggests that IV iron treatment without ESAs may substantially raise the Hb level to ≥11 g/dl in CRS patients. This treatment strategy may reduce the use of ESAs and hence its potential adverse effects.

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Stroke in hemodialysis patients randomized to different intravenous iron strategies: a prespecified analysis from the PIVOTAL trial

Kidney360 ◽

10.34067/kid.0004272021 ◽

2021 ◽

pp. 10.34067/KID.0004272021

Author(s):

Patrick B. Mark ◽

Pardeep S. Jhund ◽

Matthew R. Walters ◽

Mark C. Petrie ◽

Albert Power ◽

...

Keyword(s):

Risk Factors ◽

Stroke Risk ◽

Controlled Trial ◽

Intravenous Iron ◽

Hemodialysis Patients ◽

High Dose ◽

Pivotal Trial ◽

Increased Risk ◽

Iv Iron

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared to similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized controlled trial of intravenous iron treatment strategies in HD. Methods: We analyzed data from the Proactive IV IrOn Therapy in HaemodiALysis Patients (PIVOTAL) trial focusing on variables associated with risk of stroke. The trial randomized 2,141 adults, who had started hemodialysis <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA), to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke. Results: During a median 2.1 years follow-up, 69 (3.2%) patients experienced a first post randomization stroke. 57 (82.6%) were ischemic strokes and 12 (17.4%) hemorrhagic strokes. There were 34 post randomization strokes in the proactive arm and 35 in the reactive arm (hazard ratio (95% confidence interval): 0.90 (0.56, 1.44), p=0.66). In multivariable models, female gender, diabetes, history of prior stroke at baseline, higher baseline systolic blood pressure, lower serum albumin and higher C-reactive protein were independently associated with stroke events during follow up. Hemoglobin, total iron or ESA dose were not associated with risk of stroke. 58% of patients with a stroke event died during follow-up, compared to 23% without a stroke. Conclusions: In hemodialysis patients, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.

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