Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

BACKGROUND AND AIMS: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. METHODS: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. RESULTS: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. CONCLUSIONS: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

Intravenous iron: an update.

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion-related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.

Prevalence of iron deficiency in patients admitted to a geriatric unit: a multicenter cross-sectional study.

BACKGROUND: Iron deficiency (ID) is often associated with other comorbidities in older patients and is a factor of morbimortality. However, the prevalence of ID remains poorly documented in this population. METHODS: The CARENFER PA study was a French multicenter cross-sectional study whose objective was to evaluate ID in patients (> 75 years) admitted to a geriatric unit. The primary endpoint was the ID prevalence defined as: serum ferritin < 100 µg/L and/or transferrin saturation coefficient (TSAT) < 20%. The Short Physical Performance Battery (SPPB) test was used to identify older patients at high risk of adverse events (e.g., disability, falls, hospitalization, death). RESULTS: A total of 888 patients (mean age, 85.2 years; women, 63.5%) from 16 French centers were included from October 2022 to December 2022. The prevalence of ID was 57.6% (95% CI, 54.3-60.9) in the cohort of older patients (62.6% in anemic and 53.3% in non-anemic patients; p = 0.0062). ID prevalence increased significantly with the presence of more than three comorbidities (65.6% vs. 55.9%; p = 0.0274), CRP ≥ 12 mg/L (73.0% vs. 49.3%; p < 0.001) and treatment that may influence ID/anemia (60.5% vs. 49.6%; p = 0.0042). In multivariate analysis, only CRP ≥ 12 mg/L was an independent predictive factor of ID (odds ratio, 2.78; 95% CI, 1.92-4.08; p < 0.001). SPPB scores were low (0-6) in 60.5% of patients with ID versus 48.6% of patients without ID (p = 0.0076). CONCLUSION: More than half of older patients had ID, including non-anemic patients. ID was associated with the presence of inflammation and a low SPPB score. TRIAL REGISTRATION: NCT05514951.

The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD - the exploratory randomized controlled double-blind ExplorIRON-CKD study.

BACKGROUND: Intravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover. METHODS: The single-center double-blind randomized controlled trial "Iron and Phosphaturia - ExplorIRON-CKD" primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1-2 days following iron administration, 2 weeks, 1 month (second iron administration), 1-2 days following second administration, 2 months and 3 months following initial infusion. RESULTS: Twenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1-2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1-203.1) %; p < 0.001 and Baseline to 1-2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 - 25.4) % vs. FCM: 235.1 (138.5-434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI. CONCLUSIONS: The study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019-004370-26 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB ) (First date of trial registration: 03/12/2019).

Acceptability of IV iron treatment for iron deficiency anaemia in pregnancy in Nigeria: a qualitative study with pregnant women, domestic decision-makers, and health care providers.

BACKGROUND: Anaemia in pregnancy causes a significant burden of maternal morbidity and mortality in sub-Saharan Africa, with prevalence ranging from 25 to 45% in Nigeria. The main treatment, daily oral iron, is associated with suboptimal adherence and effectiveness. Among pregnant women with iron deficiency, which is a leading cause of anaemia (IDA), intravenous (IV) iron is an alternative treatment in moderate or severe cases. This qualitative study explored the acceptability of IV iron in the states of Kano and Lagos in Nigeria. METHODS: We purposively sampled various stakeholders, including pregnant women, domestic decision-makers, and healthcare providers (HCPs) during the pre-intervention phase of a hybrid clinical trial (IVON trial) in 10 healthcare facilities across three levels of the health system. Semi-structured topic guides guided 12 focus group discussions (140 participants) and 29 key informant interviews. We used the theoretical framework of acceptability to conduct qualitative content analysis. RESULTS: We identified three main themes and eight sub-themes that reflected the prospective acceptability of IV iron therapy. Generally, all stakeholders had a positive affective attitude towards IV iron based on its comparative advantages to oral iron. The HCPs noted the effectiveness of IV iron in its ability to evoke an immediate response and capacity to reduce anaemia-related complications. It was perceived as a suitable alternative to blood transfusion for specific individuals based on ethicality. However, to pregnant women and the HCPs, IV iron could present a higher opportunity cost than oral iron for the users and providers as it necessitates additional time to receive and administer it. To all stakeholder groups, leveraging the existing infrastructure to facilitate IV iron treatment will stimulate coherence and self-efficacy while strengthening the existing trust between pregnant women and HCPs can avert misconceptions. Finally, even though high out-of-pocket costs might make IV iron out of reach for poor women, the HCPs felt it can potentially prevent higher treatment fees from complications of IDA. CONCLUSIONS: IV iron has a potential to become the preferred treatment for iron-deficiency anaemia in pregnancy in Nigeria if proven effective. HCP training, optimisation of information and clinical care delivery during antenatal visits, uninterrupted supply of IV iron, and subsidies to offset higher costs need to be considered to improve its acceptability. Trial registration ISRCTN registry ISRCT N6348 4804. Registered on 10 December 2020 Clinicaltrials.gov NCT04976179. Registered on 26 July 2021.

Low blood level in pregnancy is of public health importance and with common occurrence worldwide, but with a higher rate in low resource settings where its burden greatly affects both the mother and her baby. This low blood level is usually caused by poor intake of an iron-rich diet. It could lead to fatigue, decreased work capacity, and dizziness if not detected. Without treatment, this condition could affect the baby, possibly leading to its sudden demise in the womb, immediately after birth, or even the woman's death.The use of oral iron has been the primary treatment; however, it is associated with significant side effects, which have led to poor compliance. Fortunately, an alternative therapy in the form of a drip has been shown to overcome these challenges. However, it is not routinely used in countries like Nigeria. Moreover, being effective is different from being utilised. Therefore, this study was conducted to understand the factors that will make this treatment widely accepted.We interviewed pregnant women, family support and health care providers in 10 health facilities in Lagos and Kano States, Nigeria. Our findings revealed good attitudes to iron drip. However, its inclusion into routine antenatal health talk, training of health care providers, availability of space, drugs and health workers who will provide this care, and ensuring this drug is of low cost are some of the efforts needed for this treatment to be accepted.

Intravenous iron infusion ameliorates anaemia and protein-losing enteropathy in patients after Fontan surgery: case series.

Protein-losing enteropathy is a severe complication of Fontan surgery and is associated with anaemia. Few studies have reported on the efficacy of an intravenous iron infusion for treating protein-losing enteropathy and low albuminemia after Fontan surgery. Herein, we present two cases of female patients who suffered from protein-losing enteropathy and low albuminemia following Fontan surgery, both of whom improved after an intravenous iron infusion.

Outcomes associated with absent blood product utilization in Jehovah's witness patients compared to the standard of care in cardiac surgery: A ten-year experience.

INTRODUCTION: For Jehovah's Witness (JW) patients requiring cardiac surgery, various strategies such as preoperative use of erythropoietin stimulating agents (ESAs), intravenous iron (IVI), and non-pharmacologic interventions have emerged to prevent complications from blood loss given transfusion is not acceptable in this population. METHODS: Retrospective case-control of cardiac surgeries performed by the same surgeon between 1/1/2011 and 8/30/2021. JW patients were matched to non-JW who received blood products and non-JW who did not receive blood products on a 1:2:2 basis. Patients were matched on procedure, age, gender, and Society of Thoracic Surgeons morbidity score. Eligible patients were aged >18 years and had a sternotomy procedure. The primary efficacy and safety outcomes included mean hematocrit values perioperatively and thrombotic events. RESULTS: A total of 27 JW, 52 non-JW transfused, and 53 non-JW not transfused patients were included in the analysis. JW patients had significantly higher mean hematocrits at every time point when compared to non-JW transfused patients and at all time points except clinic and the last recorded operating room value when compared to non-JW not transfused patients. No significant differences in thrombotic rates were found between groups, however there was a numerically higher incidence in the JW population (JW: 7.4%; non-JW transfused: 0%; non-JW not transfused: 1.9%; p = .106). CONCLUSION: A blood conservation protocol in a JW population was associated with higher perioperative hematocrit values when compared to matched controls. Further prospective study is warranted before applying similar protocols to other populations given the possibility for an increased rate of venous thromboembolism.

[Diagnosis and treatment of iron deficiency anemia].

The causes of iron deficiency anemia include blood loss, increased demand, insufficient dietary intake, and disorders affecting iron absorption. In certain circumstances, atrophic gastritis, either autoimmune or due to Helicobacter pylori infection, may contribute. On very rare occasions, iron-refractory iron deficiency anemia can develop as a consequence of TMPRSS6 mutations. Iron deficiency anemia is diagnosed by identification of microcytic hypochromic anemia with low serum ferritin levels. In cases of chronic disorders such as chronic kidney disease, chronic heart failure, and chronic inflammatory disorders, the diagnosis may also incorporate transferrin saturation. Treatment of underlying diseases is recommended along with iron supplementation. While oral iron supplements are the first choice, intravenous iron may be considered when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. Recently, high-dose intravenous iron formulations became available in Japan, but their use requires caution due to potential risks of allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage. Notably, the benefits of high-dose intravenous iron for patients with heart failure and iron deficiency are recognized in the field of cardiology. This article provides an overview, incorporating recent developments in the field of iron deficiency anemia.

Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-A 3-year experience from a single institution in Singapore.

Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.

Comparison of different intravenous iron preparations in terms of total oxidant and total antioxidant status, single center data.

Iron deficiency anemia is the most common and preventable cause of anemia. Oral and parenteral iron preparations can be used for treatment. There are some concerns about the effect on oxidative stress of parenteral preparations. In this study, we aimed to investigate the effect of ferric carboxymaltose and iron sucrose on short- and long-term oxidant-antioxidant status. The study was designed as a prospective, single-center, observational study. Patients diagnosed with iron deficiency anemia and receiving intravenous iron therapy were included. Patients were divided into 3 groups as those receiving 1000 mg iron sucrose, 1000 mg ferric carboxymaltose, and 1500 mg ferric carboxymaltose. Blood samples were collected for blood tests before treatment, at the 1st hour of the first infusion, and at the 1st month of follow-up. The total oxidant and total antioxidant status were analyzed to evaluate oxidative stress and antioxidant status. Fifty-eight patients are included. Nineteen patients received iron sucrose 1000 mg (G1), 21 patients received ferric carboxymaltose 1000 mg (G2), and 18 patients received ferric carboxymaltose 1500 mg (G3). First hour total antioxidant status was higher in the iron sucrose group than in the ferric carboxymaltose group [G1 and G2 (p = 0.027), G1 and G3 (p = 0.004)]. At the 1st hour, total oxidant status was higher in iron sucrose group than in ferric carboxymaltose group [G1 and G2 (p = 0.016), G1 and G3 (p = 0.011)]. There was no difference in total oxidant and antioxidant stress between the three treatment groups at the 1st month evaluation [p: 0.19 and p: 0.12]. Total oxidant and antioxidant status in iron sucrose and ferric carboxymaltose formulations were found to be higher in the iron sucrose group in the acute period at the 1st hour after infusion. There was no significant difference between antioxidant and oxidant total status in all three treatment groups at the 1st month of long-term control. The fact that total oxidant status was lower in the ferric carboxymaltose group containing high-dose treatment compared to iron sucrose according to the 1st hour change showed that high-dose iron did not significantly affect oxidant stress in the short term. In addition, long-term oxidant stress evaluation at the 1st month did not show any difference between iron preparations. In conclusion, it has been shown that high-dose intravenous iron therapy, which is easier to use in clinical practice, has no effect on the oxidant-antioxidant system.

A case of intravenous iron administration resulting in cerebral edema expansion.

BACKGROUND: Iron plays an important role in the development of perihematomal edema (PHE) in the setting of intracerebral hemorrhage (ICH). Cerebral iron is increased via direct hemoglobin release in ICH, and several studies have investigated the use of iron-chelating agents to mitigate its toxicity. However, the effect of systemic iron administration, corroborating the reverse concept, has never been investigated or reported clinically. We report the first case of systemic iron administration in the setting of hemorrhagic traumatic brain injury (TBI). CASE PRESENTATION: A 46-year-old woman was admitted to the hospital with acute moderate-to-severe TBI. Her head computed tomography (CT) scan showed bifrontal hemorrhagic contusions with mild PHE. She was started on hypertonic saline 3% continuous infusion and her condition remained stable initially. She was found to be anemic and was given intravenous iron sucrose. Shortly after iron administration, her mental status declined, and left pupil became dilated and sluggish. Repeat CT demonstrated significantly worsening PHE. This prompted maximum hyperosmolar therapy and external ventricular drain (EVD) placement which both were weaned off slowly due to liable ICPs. She was discharged home after a 25-day hospital stay. CONCLUSIONS: We believe this is the first report of exacerbating PHE accompanied by clinical decline after intravenous iron administration in the setting of acute hemorrhagic brain contusions. Though the effects of systemic iron administration on brain edema and the treatments targeting cerebral iron are poorly understood, the administration of systemic iron in acute TBI seems to be detrimental. More research is needed to address iron toxicity in TBI. Our case adds to the growing evidence for such a pathway in the treatment of ICH and TBI.

Methodology and Baseline Data of a Comparative Exploratory Double-Blinded Randomized Study of Intravenous Iron on Fibroblast Growth Factor 23 and Phosphate in Chronic Kidney Disease.

Modern intravenous iron compounds (e.g., ferric carboxymaltose [FCM] and ferric derisomaltose [FDI]) are utilized in the treatment of iron deficiency anemia in non-dialysis-dependent chronic kidney disease (ND-CKD). Product-specific alterations in the metabolism of fibroblast growth factor 23 (FGF-23) leading to hypophosphatemia have been described for certain intravenous iron compounds, such as FCM, with potential effects on bone and cardiovascular health and quality of life. No prior head-to-head comparison between FCM and FDI exists in ND-CKD. This single-center exploratory double-blind randomized controlled trial primarily aimed to investigate the differential impact of FCM and FDI on FGF-23 and phosphate in patients with iron deficiency +/- anemia and ND-CKD (stages 3a-5 - serum ferritin <200 µg/L or serum ferritin 200-299 µg/L and transferrin saturation <20%). Patients were randomized (1:1) to receive either FCM or FDI over two infusions (1 month apart). Follow-up was 3 months. Measurements of serum intact FGF-23, phosphate, vitamin D metabolites, parathyroid hormone, other bone metabolism, cardiovascular, and quality of life markers were monitored. 168 patients were prescreened. Thirty-five patients were screened; 26 patients were randomized. The mean (standard deviation) age was 67.9 (12.4) years and 17 participants were male. Most participants had stage 4 CKD (median [interquartile range] estimated glomerular filtration rate [eGFR]: 18.0 [11.3] mL/min/1.73 m2). A higher than normal median (interquartile range) level of intact FGF-23 (212.1 [116.4] pg/mL) was noted. Serum phosphate was within normal range, while parathyroid hormone was higher and 1,25 (OH)2 vitamin D lower than the normal range. The "Iron and Phosphaturia - ExplorIRON-CKD" trial will provide important information regarding the differential effect of intravenous iron products in terms of FGF-23, phosphate, and other markers of bone and cardiovascular metabolism, alongside patient-reported outcome measures in patients with ND-CKD.

The ICaRAS randomised controlled trial: Intravenous iron to treat anaemia in people with advanced cancer - feasibility of recruitment, intervention and delivery.

BACKGROUND: Anaemia is highly prevalent in people with advanced, palliative cancer yet sufficiently effective and safe treatments are lacking. Oral iron is poorly tolerated, and blood transfusion offers only transient benefits. Intravenous iron has shown promise as an effective treatment for anaemia but its use for people with advanced, palliative cancer lacks evidence. AIMS: To assess feasibility of the trial design according to screening, recruitment, and attrition rates. To evaluate the efficacy of intravenous iron to treat anaemia in people with solid tumours, receiving palliative care. DESIGN: A multicentre, randomised, double blind, placebo-controlled trial of intravenous iron (ferric derisomaltose, Monofer®). Outcomes included trial feasibility, change in blood indices, and change in quality of life via three validated questionnaires (EQ5D5L, QLQC30, and the FACIT-F) over 8 weeks. (ISRCTN; 13370767). SETTING/PARTICIPANTS: People with anaemia and advanced solid tumours who were fatigued with a performance status ⩽2 receiving support from a specialist palliative care service. RESULTS: 34 participants were randomised over 16 months (17 iron, 17 placebo). Among those eligible 47% of people agreed to participate and total study attrition was 26%. Blinding was successful in all participants. There were no serious adverse reactions. Results indicated that intravenous iron may be efficacious at improving participant haemoglobin, iron stores and select fatigue specific quality of life measures compared to placebo. CONCLUSION: The trial was feasible according to recruitment and attrition rates. Intravenous iron increased haemoglobin and may improve fatigue specific quality of life measures compared to placebo. A definitive trial is required for confirmation.

Impact of postoperative intravenous iron therapy on postoperative infections in older patients with severe anaemia after hip fracture surgery.

BACKGROUND: Anaemia is common following hip fracture in ortho-geriatric patients and is associated with postoperative infections.. This study investigated whether intravenous iron supplements reduced the rate of postoperative infections within 30 days postoperatively in older adults after hip fracture surgery. METHODS: This observational study included 198 ortho-geriatric patients July 2018-May 2020. In May 2019 a local guideline was implemented and recommended II therapy on the 3rd postoperative day if haemoglobin concentration was < 6.5 mmol/L after hip fracture surgery. RESULTS: The patients were divided into four treatment groups: blood transfusion (n = 44), IV iron (n = 69), blood transfusion + IV iron (n = 35) and no treatment (n = 50). The number of patients who had an infection within 30 days was similar in the two time periods (38.8% before vs. 38.9% after systematic I.V. iron supplementation, P = 1.00) and no significant difference according to risk of infection was found between treatment groups. CONCLUSION: This study documents no effect of intravenous iron supplements on postoperative infections in older adults after hip fracture surgery. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Authority (2008-58-0028) the 2th of September 2019.

Investigation on the feasibility of large-volume autologous red blood cells donation: A pilot trial in a small cohort of Chinese.

BACKGROUND: Preoperative autologous blood donation (PAD) is used for elective surgical procedures with a predictable blood loss. But a downward trend in PAD is due to the fact that patients with preoperative whole blood donation or two-unit red cell apheresis cannot avoid receiving allogenic blood during intensive surgery. To improve the clinical application of PAD, this study explores the feasibility of large-volume autologous red blood cells (RBCs) donation by a pilot trial in a small cohort of Chinese. METHODS: This was a single-center, prospective study and 16 male volunteers were enrolled from May to October in 2020. Each volunteer donated 627.25 ± 109.74 mL (mean ± SD) RBC with apheresis machine or manually, and received 800 mg of intravenous iron in four divided doses. Blood pressure, oxygen saturation (SpO2 ), respiratory rate and heart rate were monitored throughout the procedure. The RBC count, hemoglobin (Hb) concentration, hematocrit (Hct), reticulocyte count, erythropoietin (Epo), serum iron, total iron binding capacity (TIBC), transferrin saturation, transferrin, and ferritin were dynamically detected and analyzed before and 8 weeks after blood donation. RESULTS: There was no differences in SpO2 , systolic and diastolic blood pressure before and after blood collection (P ≥ .05). The heart rate and respiratory rate after donation were slightly lower than those before (P < .05). The level of RBC, Hb concentration and Hct fell to a nadir on Day 3 (pre-donation vs post-donation on Day 3: RBC 4.81 ± 0.36*1012 /L vs 3.65 ± 0.31, P < .05; Hb 148.59 ± 11.92 g/L vs 113.19 ± 10.43 g/L, P < .05; Hct 44.08 ± 3.06% vs 33.38 ± 2.57%, P < .05) and recovered to the pre-donation levels at the eighth week post donation (pre-donation vs post-donation at the eighth week: RBC 4.81 ± 0.36*1012 /L vs 4.84 ± 0.34*1012 /L, P ≥ .05; Hb 148.59 ± 11.92 g/L vs 150.91 ± 11.75 g/L, P ≥ .05; Hct 44.08% ± 3.06% vs 43.86 ± 3.06%, P ≥ .05). Epo and the reticulocyte count reached the peak values on Days 1 and 7, respectively (Epo: D0 15.30 ± 7.47 mlU/ML vs D1 43.26 ± 10.52 mlU/ML, P < .05; reticulocyte count: D0 0.07 ± 0.02*109 /L vs D7 0.17 ± 0.04*109 /L, P < .05). The red cell net profits on Day 7, the second, fourth and eighth week postdonation were 160.39 ± 144.33 mL, 387.59 ± 128.74 mL, 530.95 ± 120.37 mL, and 614.18 ± 120.10 mL, and accounted for 27.47% ± 24.70%, 63.75% ± 24.91%, 86.20% ± 22.99%, and 99.20% ± 19.19% of RBC donation, respectively. The levels of serum iron, serum ferritin, and transferrin saturation increased during the first week because of the supplement of intravenous iron, and then gradually decreased and declined to the baseline at the end of the study period at the eighth week. CONCLUSIONS: The large-volume autologous RBCs donation of 600 mL is proved safe in our study. Combination support of normal saline to maintain blood volume and intravenous iron supplementation may ensure the safety and effectiveness of large-volume RBC apheresis.

Efficacy of immediate postoperative intravenous iron supplementation after staged bilateral total knee arthroplasty.

BACKGROUND: Approximately 26% of patients undergoing major orthopedic elective procedures have preoperative anemia. This study aimed to investigate the effect of intravenous (IV) iron supplementation on the hemoglobin (Hb) level after staged bilateral total knee arthroplasty (TKA) in patients with or without preoperative anemia. METHODS: We retrospectively analyzed 418 patients who underwent staged bilateral TKA (1 week interval). The iron group (n = 220) received IV iron isomaltoside immediately after each TKA. The no-iron group (n = 198) was recommended to receive transfusion if postoperative anemia was diagnosed between the first and second TKA. Preoperative anemia was present in 42 (21.2%) and 50 (22.7%) patients in the no-iron and iron groups, respectively. Demographic data, preoperative and postoperative Hb levels, Hb level change (preoperative minus postoperative 6-week Hb level), and blood drainage amount were compared between groups. RESULTS: The transfusion rate was lower in the iron group than in the no-iron group (96.5% vs. 58.6%, P < 0.001). Overall, the demographic data, preoperative and postoperative 6-week Hb levels, Hb level change, and blood drainage amount were not significantly different between the two groups. Among patients with preoperative anemia, the iron group showed lower Hb level change (0.6 ± 0.9 vs. 0.1 ± 1.1, P = 0.016). CONCLUSION: Patients with preoperative anemia treated with IV iron showed lower Hb level change than did those without IV iron treatment. Despite the lower transfusion rate, the iron group showed similar postoperative 6-week Hb level and Hb level change to the no-iron group.

Ferric derisomaltose for the treatment of iron deficiency anemia with postpartum hemorrhage: Results of a single-arm, open-label, phase 3 study in Japan.

AIM: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). METHODS: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk. RESULTS: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI. CONCLUSIONS: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. CLINICAL TRIAL IDENTIFIER: JapicCTI-194888.

Pathophysiology and Treatment Opportunities of Iron Deficiency in Heart Failure: Is There a Need for Further Trials?

PURPOSE OF REVIEW: Iron deficiency (ID) complicates heart failure (HF) at different stages of the natural history of the disease; however, this frequent comorbidity is still not comprehensively understood and investigated in terms of pathophysiology. Intravenous iron therapy with ferric carboxymaltose (FCM) should be considered to improve the quality of life, exercise capacity, and symptoms in stable HF with ID, as well as to reduce HF hospitalizations in iron-deficient patients stabilized after an episode of acute HF. The therapy with intravenous iron, however, continues to generate important clinical questions for cardiologists. RECENT FINDINGS: In the current paper, we discuss the class effect concept for intravenous iron formulations beyond FCM, based on the experiences of nephrologists who administer different intravenous iron formulations in advanced chronic kidney disease complicated with ID and anemia. Furthermore, we discuss the neutral effects of oral iron therapy in patients with HF, because there are still some reasons to further explore this route of supplementation. The different definitions of ID applied in HF studies and new doubts regarding possible interactions of intravenous iron with sodium-glucose co-transporter type 2 inhibitors are also emphasized. The experiences of other medical specializations may provide new information on how to optimally replenish iron in patients with HF and ID.

Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial.

PURPOSE: To compare the efficacy of intravenous (IV) iron (ferric derisomaltose) with oral iron (ferrous fumarate) in women 14-21 weeks pregnant with persistent iron deficiency (ferritin < 30 µg/L). METHODS: In a single-centre, open-label, randomised controlled trial at a Danish hospital, women with persistent iron deficiency after routine oral iron treatment were allocated to receive 1000 mg IV iron (single-dose) or 100 mg elemental oral iron daily. Outcomes were assessed during an 18-week follow-up period. The primary endpoint was the proportion of non-anaemic (haemoglobin [Hb] ≥ 11 g/dL) women throughout follow-up. Other outcomes included changes in haematological parameters, patient-reported fatigue, and quality of life (QoL). Safety was assessed by recording adverse events. RESULTS: From July 2017 to February 2020, 100 women were randomised to IV iron and 101 to oral iron. Throughout follow-up, 91% of women were non-anaemic in the IV iron group compared with 73% in the oral iron group (18% difference [95% confidence interval 0.10-0.25]; p < 0.001). The mean Hb increase was significantly greater with IV iron versus oral iron at Weeks 6 (0.4 versus - 0.2 g/dL; p < 0.001), 12 (0.5 versus 0.1 g/dL; p < 0.001), and 18 (0.8 versus 0.5 g/dL; p = 0.01). Improvements in fatigue and QoL were greater with IV iron versus oral iron at Weeks 3 and 6. The incidence of treatment-related adverse events was comparable between treatment groups. CONCLUSION: IV iron was superior in preventing anaemia compared with oral iron in pregnant women with persistent iron deficiency; biochemical superiority was accompanied by improved fatigue and QoL. CLINICAL TRIAL REGISTRATION: European Clinical Trials Database: EudraCT no.: 2017-000776-29 (3 May 2017); ClinicalTrials.gov: NCT03188445 (13 June 2017). The trial protocol has been published: https://dx.doi.org/10.1186%2Fs13063-020-04637-z .

What we should consider to facilitate recovery of the hematological profile in all patients after pancreaticoduodenectomy: the role of preoperative intravenous iron treatment.

BACKGROUND: In pancreaticoduodenectomy (PD), the duodenum and upper jejunum responsible for iron absorption are removed, which can lead to massive hemorrhage during surgery and cause iron deficiency anemia after PD. The aim of this study was to evaluate overall changes in hematologic profiles of patients who underwent pancreaticoduodenectomy. Effect of preoperative intravenous iron treatment on recovery of anemia after surgery was also investigated. METHODS: From March 2021 to December 2021, patients who underwent curative PD at our institution due to periampullary lesions were enrolled. They were divided into two groups according to whether or not iron was administered before surgery. In the IV iron group, all patients had been routinely administered with 1000 mg of ferric carboxymaltose intravenously once about 3-7 days before the operation day. Contrarily, patients in the control group did not receive intravenous iron before PD. Changes in hematological profile were measured preoperatively and at 5, 14, and 30 days postoperatively. Clinical results of the two groups were compared and analyzed. Additionally, a subgroup analysis was performed for selected non-anemic patients who had preoperative hemoglobin level of 12.0 g/dl or higher to compare changes in hematologic profiles between the two groups. RESULTS: Thirty patients of the IV iron group and 34 patients of the control group were analyzed. Although no difference was observed in postoperative complications or mortality, hemoglobin and iron levels were recovered significantly faster at two weeks postoperatively in the IV iron group than in the control group. Iron levels were significantly higher in the IV iron group throughout the postoperative period. In subgroup analysis conducted for non-anemic patients, hemoglobin levels were recovered significantly faster and maintained higher in the IV iron group throughout the postoperative period, although baseline levels of hemoglobin were similar between the two groups. In addition, the length of intensive care unit stay was significantly shorter in the IV iron group than in the control group. CONCLUSIONS: Preoperative intravenous iron treatment might be effective in facilitating recovery of hematologic profiles of patients during the recovery period after PD regardless of the presence of preoperative anemia, thus preventing postoperative iron deficiency anemia.