Pathophysiology and management of iron deficiency anaemia in pregnancy: a review.

According to World Health Organization (WHO), iron deficiency anaemia (IDA) is considered the most prevalent nutritional deficiency worldwide, affecting approximately 30% of the global population. While gastrointestinal bleeding and menstruation in women are the primary causes of IDA, insufficient dietary iron intake and reduced iron absorption contribute to the condition. The aim of IDA treatment is to restore iron stores and normalise haemoglobin levels in affected patients. Iron plays a critical role in various cellular mechanisms, including oxygen delivery, electron transport, and enzymatic activity. During pregnancy, the mother's blood volume increases, and the growing foetus requires a significant increase in iron. Iron deficiency during pregnancy is associated with adverse outcomes such as maternal illness, low birth weight, preterm birth, and intrauterine growth restriction. Iron supplementation is commonly used to treat IDA; however, not all patients benefit from this therapy due to factors such as low compliance and ineffectiveness. In the past, IV iron therapy was underutilised due to its unfavourable and occasionally unsafe side effects. Nevertheless, the development of new type II and III iron complexes has improved compliance, tolerability, efficacy, and safety profiles. This article aims to provide an updated overview of the diagnosis and management of IDA during pregnancy. It will discuss the advantages and limitations of oral versus intravenous iron and the pathophysiology, diagnosis, treatment, and overall management of IDA in pregnancy.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Intravenous Iron Therapy in Heart Failure.

Iron deficiency anemia is both a comorbid condition and an indicator of poor prognosis in heart failure. The mechanisms by which this occurs are multiple and complex. Recent robust randomized clinical trials have shown significant improvements in quality of life and rates of hospitalization with intravenous repletion of iron. In this article, we review the mechanisms by which iron deficiency impacts heart failure and the evidence behind repletion. There remains a good deal to learn about long-term effects of intravenous iron repletion, and clinical trials are ongoing in this regard.

Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study.

PURPOSE: Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL). MATERIALS AND METHODS: The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL. RESULTS: There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated. CONCLUSION: In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Anemia management protocols in hemodialysis (HD) units differ conspicuously regarding optimal intravenous (IV) iron dosing; consequently, patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents (ESAs). Complementary to IV iron safety studies, our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb, TSAT, ferritin, and ESA dose in common clinical practice. METHODS: 9,471 HD patients (11 countries, 2009-2011) in the DOPPS, a prospective cohort study, were analyzed. Associations of IV iron dose (3-month average, categorized as 0, <300, ≥300 mg/month) with 3-month change in Hgb, TSAT, ferritin, and ESA dose were evaluated using adjusted GEE models. RESULTS: Relative change: Monotonically positive associations between IV iron dose and Hgb, TSAT, and ferritin change, and inverse associations with ESA dose change, were observed across multiple strata of prior Hgb, TSAT, and ferritin levels. Absolute change: TSAT, ferritin, and ESA dose changes were nearest zero with IV iron <300 mg/month, rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing. Findings were robust to numerous sensitivity analyses. CONCLUSIONS: Though residual confounding cannot be ruled out in this observational study, findings suggest that IV iron dosing <300 mg/month, as commonly seen with maintenance dosing of 100-200 mg/month, may be a more effective approach to support Hgb than the higher IV iron doses (300-400 mg/month) often given in many European and North American hemodialysis clinics. Alongside studies supporting the safety of IV iron in 100-200 mg/month dose range, these findings help guide the rational dosing of IV iron in anemia management protocols for everyday hemodialysis practice.

Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial. STUDY DESIGN: Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION: Patients with CKD stages 3 to 5 or 5D. SELECTION CRITERIA FOR STUDIES: All randomized controlled trials, regardless of publication status or language. INTERVENTION: IV versus oral iron supplementation. OUTCOMES: The primary outcome was defined as percentage of patients reaching an elevation in hemoglobin (Hb) concentration > 1g/dL. Secondary end points included percentage of patients who reached Hb levels > 11g/dL, absolute Hb concentration, change in Hb concentration, transferrin saturation, ferritin levels, erythropoiesis-stimulating agents and blood transfusion requirement, and quality of life. Safety analysis included all-cause mortality and serious and all adverse events. RESULTS: 24 trials were identified, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D. Patients treated with IV iron were more likely to reach an Hb response > 1g/dL (risk ratios [RRs] of 1.61 [95% CI, 1.39-1.87] for CKD stages 3-5 and 2.14 [95% CI, 1.68-2.72] for CKD stage 5D). Safety analysis showed similar rates of mortality and serious and any adverse effects. IV iron replacement was associated with higher risk for hypotension (RR, 3.71; 95% CI, 1.74-7.94) and fewer gastrointestinal adverse events (RR, 0.43; 95% CI, 0.28-0.67). LIMITATIONS: Significant heterogeneity between trials; follow-up was usually limited to 3 months. CONCLUSIONS: Our results agree with current recommendations for IV iron replacement for patients with CKD stage 5D and support increased use of IV iron for patients with CKD stages 3 to 5.

Utility and cost of low-vacuum reinfusion drains in patients undergoing surgery for subcapital hip fracture repair. A before and after cohort study.

BACKGROUND: Postoperative blood loss may be a risk factor for allogeneic blood transfusion (ABT) in patients undergoing subcapital hip fracture (SHF) repair. We investigated the utility and costs of using a low-vacuum reinfusion drain (Bellovac ABT) within a blood management protocol for reducing ABT requirements in consecutive SHF. METHODS: The blood management protocol consisted of the application of a restrictive transfusion trigger (Hb < 8 g/dl), the peri-operative administration of IV iron sucrose (3 × 200 mg/48 h) ± recombinant erythropoietin (1 × 40 000 IU sc) and the use of Bellovac ABT (Group 2, n = 117). An immediate previous SHF series managed without Bellovac ABT served as control (Group 1, n = 138). RESULTS: Overall, 72 out of 255 (28%) received at least one ABT unit (2·1 ± 1·0 U/transfused patient) without differences between groups. However, in the subgroup of patients with admission Hb < 13 g/dl, the use of Bellovac ABT reduced postoperative ABT rates (16% vs. 46%, for groups 2 and 1, respectively; P = 0·001), although only 3 were reinfused, and was cost-saving. The use of Bellovac ABT also resulted in fewer wound bleeding complications, but there were no differences in Hb at postoperative days 7 and 30 between groups. CONCLUSIONS: In SHF patients with admission Hb < 13 g/dl and managed with peri-operative IV iron ± recombinant erythropoietin plus restrictive transfusion indication, the use of Bellovac ABT was associated with reduced ABT requirements, without increasing postoperative complications, and cost-savings.

Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Intravenous iron-induced hypophosphatemia and kidney stone disease.

Patients with Crohn's disease are at increased risk for symptomatic nephrolithiasis. Stones in these patients are most commonly composed of calcium oxalate monohydrate or mixed calcium-oxalate and calcium-phosphate. Precipitation of both minerals depends on urinary pH, calcium, phosphate and oxalate excretion. The present manuscript reports on two patients with Crohn's disease and bowel resection, in whom the onset of symptomatic urolithiasis occurred after repeated infusions of ferric carboxymaltose - a drug, which is known to cause hyperphosphaturia. The present study shows that ferric carboxymaltose-induced hyperphosphaturia can be associated with kidney stone formation and symptomatic urolithiasis, especially in patients treated with calcitriol. Calcitriol has been shown to mitigate ferric carboxymaltose-induced secondary hyperparathyroidism and hyperphosphaturia, but is known to increase urinary calcium excretion. Chemical analysis of recovered stones revealed that they were mixed calcium oxalate and phosphate stones. Ring-like deposition of iron detected by spatially resolved elemental analysis using laser ablation-inductively coupled plasma mass spectrometry, showed that the stones also contained iron. Based on our findings, we propose that patients with inflammatory bowel disease requiring intravenous iron therapy should be carefully monitored for the development of hypophosphatemia and urolithiasis. If hypophosphatemia occurs in such patients, calcitriol should be used with caution.

Describing and Comparing Patient Factors Associated with Use of Parenteral Iron before and after Implementation of an Order Set for Parenteral Iron (DECODE IRON).

Background: In select clinical scenarios, IV administration of iron is suitable for management of iron deficiency anemia; however, for most patients, oral administration of iron is the mainstay of treatment. At the Red Deer Regional Hospital Centre, in Red Deer, Alberta, high utilization of IV iron has resulted in limited access to this medication for the treatment of ambulatory patients, as well as significant usage of health care resources. Objectives: The primary objective was to compare patient characteristics, specifically pretreatment laboratory test results and previous use of oral iron, among those receiving IV iron therapy in an ambulatory setting before and after implementation of an iron sucrose order set. For secondary objectives, the aforementioned groups were compared with regard to meeting the diagnostic criteria for iron deficiency anemia, with or without pretreatment oral iron or blood transfusion, and the dosing characteristics for IV iron. Methods: A retrospective electronic chart review was performed for ambulatory patients who received IV iron between January 1, 2020, and January 31, 2022. Results: A total of 436 unique treatment courses were included in the analysis. The following pretreatment laboratory results were observed before and after implementation of the iron sucrose order set: mean hemoglobin 105.8 (standard deviation [SD] 21.9) g/L versus 102.2 (SD 18.5) g/L; mean of mean corpuscular volume (MCV) 82.2 (SD 9.4) fL versus 79.2 (SD 8.9) fL; and median ferritin 7 (interquartile range [IQR] 4-12) µg/L versus 6 (IQR 4-11) µg/L. Only the difference in MCV values was statistically significant (p = 0.001). Conclusions: The implementation of an iron sucrose order set for ambulatory patients did not have a significant effect on pretreatment laboratory parameters among patients for whom IV iron was prescribed. Further stewardship initiatives could be beneficial in improving the appropriateness of IV iron use.

Contexte: Dans certains scénarios cliniques, l'administration de fer par voie intraveineuse (IV) convient à la prise en charge de l'anémie ferriprive; cependant, pour la plupart des patients, l'administration de fer par voie orale constitue le pilier du traitement. Au centre hospitalier régional Red Deer, à Red Deer, en Alberta, l'utilisation élevée du fer par IV a entraîné un accès limité à ce médicament pour le traitement des patients ambulatoires, ainsi qu'une utilisation importante des ressources de santé. Objectifs: L'objectif principal consistait à comparer les caractéristiques des patients, en particulier les résultats de tests de laboratoire avant traitement et l'utilisation antérieure de fer par voie orale, chez ceux recevant un traitement de fer par IV en milieu ambulatoire avant et après la mise en oeuvre d'un protocole de prescription de fer sucrosé. Les objectifs secondaires, quant à eux, étaient la comparaison des groupes susmentionnés en ce qui concerne la satisfaction des critères diagnostiques de l'anémie ferriprive, avec ou sans prétraitement de fer administré par voie orale ou par transfusion sanguine, ainsi que les caractéristiques posologiques du fer administré par IV. Méthodes: Un examen rétrospectif des dossiers électroniques a été réalisé pour les patients ambulatoires ayant reçu du fer par IV entre le 1er janvier 2020 et le 31 janvier 2022. Résultats: Au total, 436 traitements uniques ont été inclus dans l'analyse. Les résultats suivants de tests de laboratoire avant traitement ont été observés avant et après la mise en oeuvre du protocole de prescription de fer sucrosé: hémoglobine moyenne 105,8 g/L (écart type [ÉT] 21,9) contre 102,2 g/L (ÉT 18,5); moyenne du volume corpusculaire moyen (VCM) 82,2 fL (ÉT 9,4) contre 79,2 fL (ÉT 8,9); et ferritine médiane 7 µg/L (intervalle interquartile [IIQ] 4­12) contre 6 µg/L (IQR 4­11). La seule différence statistiquement significative concernait les valeurs VCM (p = 0,001). Conclusions: La mise en oeuvre d'un protocole de prescription de fer sucrosé pour les patients ambulatoires n'a pas eu d'effet significatif sur les paramètres biologiques avant traitement chez les patients pour lesquels du fer par IV a été prescrit. D'autres initiatives de gestion pourraient être bénéfiques pour améliorer la pertinence de l'utilisation du fer IV.

Ferric carboxymaltose for iron deficiency in patients with heart failure: a systematic review and meta-analysis.

Aim: Iron deficiency (ID) is associated with heart failure (HF) in a considerable proportion of patients. To improve the quality of life, lower the frequency of hospitalizations, and lower mortality rates of chronic HF patients (HF), this meta-analysis will look into the role of iron supplementation using ferric carboxymaltose (FCM). Methods & results: From inception until 1 October 2023, we conducted a thorough literature search of electronic databases for peer-reviewed publications. Around 5229 HF patients were included, of which 2691 received FCM while 2538 received placebo. Conclusion: FCM reduces HF-related hospitalizations but doesn't improve overall or cardiovascular mortality in those with HF and ID. The overall results support FCM's role in managing iron deficiency in heart failure.

Heart failure (HF) patients often suffer from iron deficiency (ID), worsening their symptoms and quality of life. Intravenous iron therapy, like ferric carboxymaltose (FCM), has been studied for its benefits in HF. This meta-analysis looked at existing research and found that FCM treatment reduced hospitalizations for HF but didn't significantly impact overall mortality. Although FCM improves patients' lives, more research is needed to understand its long-term effects fully. This study highlights the importance of addressing ID in HF management and supports FCM therapy as a beneficial option for HF patients.

Fetal bradycardia and acidosis during maternal parenteral iron: Case reports and literature review.

Iron deficiency anemia is an important problem among pregnant women, and intravenous (IV) iron infusions have been increasingly used. Whether fetal monitoring is required during infusion has been debated, with a recent guideline by Hematologists recommending against such. We report two cases of fetal bradycardia after iron isomaltoside (IIM), in women with otherwise good maternal and fetal health. Both developed dyspnea with desaturation minutes from infusion, followed by persistent fetal bradycardia. Both underwent category 1 CS, with cord arterial pH of 7.08 and 6.94 respectively. Upon literature review, only three case reports on fetal bradycardia in IV iron were identified. For older IV iron formulations, a case was reported after IV dextran test dose, while two cases after ferric gluconate were reported. For the new formulation IIM, only one case was reported so far, but in a woman with Crohn's disease and intrauterine growth restriction. IV iron in pregnancy carries risk of anaphylactic or hypersensitivity reactions, even with the newest formulations and in women with good maternal and fetal health. While rarely reported so far, fetal bradycardia is a possible consequence, commonly preceded by respiratory symptoms. Fetal monitoring should therefore be considered during infusion.

Update on iron supplementation in patients with cancer-related anemia.

INTRODUCTION: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal. AREAS COVERED: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects. EXPERT OPINION: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Cost-effectiveness analysis of parenteral iron therapy compared to oral iron supplements in managing iron deficiency anemia among pregnant women.

OBJECTIVE: This study compared the clinical efficacy and cost-effectiveness of parenteral iron, using intravenous iron sucrose (IVIS) therapy against the standard regimen of oral iron (OI) therapy for managing iron-deficiency anemia (IDA) among pregnant women in a natural primary care setting in Gujarat. DESIGN: A prospective cost-effectiveness study was conducted in natural programme setting wherein 188 pregnant women in their 14 to 18 weeks with moderate and severe anemia women enrolled from two districts of Gujarat, and 142 were followed up until the post-partum phase. The intervention group comprised of 82 participants who were administered IVIS, while the comparison group comprised of 106 participants who were put on OI therapy. Hemoglobin (Hb) levels were measured at periodic intervals, first during enrollment and then during each month of pregnancy period and finally on the 42nd day of the post-natal period. OUTCOME MEASURES: Change in mean Hb level from baseline was the primary outcome, while the incidence of morbidity and mortality was a secondary outcome measure. RESULTS: The intervention group showed a significant incremental mean change in Hb level from 8.2 g/dl to 11.45 g/dl at the fourth follow-up, while the control group's mean Hb level reduced from 9.99 g/dl to 9.55 g/dl. The discounted cost per beneficiary for IVIS was US$ 87, while that for OI was US$ 49. The incremental cost-effectiveness ratio (ICER) was US$ 9.84, which is 0.049% of India's per capita GDP. CONCLUSION: IVIS therapy was more clinically effective and cost-effective than OI therapy among pregnant women for management of moderate and severe anemia.

Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.

Background: Randomized clinical trials (RCTs) evaluating the role of intravenous (IV) iron administration in patients with heart failure (HF) and iron deficiency (ID) have yielded inconsistent results. Methods: Electronic search of MEDLINE, EMBASE and OVID databases was performed until November 2022 for RCTs that evaluated the role of IV iron administration in patients with HF and ID. The main study outcomes were the composite of HF hospitalization or cardiovascular mortality, and individual outcome of HF hospitalization. Summary estimates were evaluated using random effects model. Results: The final analysis included 12 RCTs with 3,492 patients (1,831 patients in the IV iron group and 1,661 patients in the control group). The mean follow-up was 8.3 months. IV iron was associated with a lower incidence in the composite of HF hospitalization or cardiovascular mortality (31.9% vs. 45.3%; relative risk [RR] 0.72; 95% confidence interval [CI] 0.59-0.88) and individual outcome of HF hospitalization (28.4% vs. 42.2; RR 0.69; 95% CI 0.57-0.85). There was no significant difference between both groups in cardiovascular mortality (RR 0.88; 95% CI 0.75-1.04) and all-cause mortality (RR 0.95; 95% CI 0.83-1.09). IV iron was associated with lower New York Heart Association class and higher left ventricular ejection fraction (LVEF). Meta-regression analyses showed no effect modification for the main outcomes based on age, hemoglobin level, ferritin level or LVEF. Conclusion: Among patients with HF and ID, IV iron administration was associated with reduction in the composite of HF hospitalization or cardiovascular mortality and driven by a reduction in HF hospitalization.

Intravenous iron for treatment of iron deficiency anemia during pregnancy and associated maternal outcomes.

BACKGROUND: More than 40% of pregnant patients worldwide are anemic, with at least half resulting from iron deficiency anemia (IDA). Anemia in pregnancy is linked with adverse maternal and neonatal outcomes. Treatment for IDA is iron supplementation; however, the optimal route of administration remains unclear. We sought to investigate whether patients with IDA who received intravenous iron (IVI) had decreased odds of maternal morbidity compared to patients who did not. METHODS: This is a retrospective cohort study of pregnant patients with presumed IDA with term deliveries at a tertiary hospital from 2013-2021. Data were extracted from the hospital's electronic medical record using standardized definitions and billing codes. Patients who received antepartum IVI were compared to patients who did not. The primary outcome was a maternal morbidity composite inclusive of receipt of blood transfusion, hysterectomy, admission to the intensive care unit or death. Bivariate analyses and multivariable logistic regression modelling were performed adjusting for potential confounders. RESULTS: Of 45,345 pregnancies, 5054 (11.1%) met eligibility criteria. Of these, 944 (18.7%) patients received IVI while 4110 (81.3%) did not. Patients who received IVI had higher risk baseline characteristics. They experienced a greater increase in hematocrit from pregnancy nadir to delivery admission (4.5% vs. 3.3%, p < .01). Despite this, patients who received IVI had higher odds of the maternal morbidity composite (OR 1.47, 95%CI 1.11-1.95). This finding persisted after adjusting for potential confounders, although the strength of the association became attenuated (aOR 1.37, 95%CI 1.02-1.85). Odds of the morbidity composite were not elevated among patients who received a full IVI treatment course (OR 1.2, 95% CI 0.83-1.90). DISCUSSION: Odds of the maternal morbidity composite were increased among patients who received IVI despite greater increases in hematocrit. The effect was attenuated after adjusting for potential confounders and was not significant among patients who completed a full treatment course.

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Background: Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. Objectives: To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. Methods: This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. Results: A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 µg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. Conclusion: This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Contexte: L'anémie ferriprive est fréquente chez les patients atteints d'insuffisance rénale chronique avancée (IRC). Une seule dose de dérisomaltose ferrique (FDI) permet au niveau de fer de se rétablir, contrairement à d'autres formes de fer administrées par IV qui nécessitent, elles, plusieurs doses. Des protocoles sont couramment utilisés avec d'autres fers administrés par IV, mais les données canadiennes sur le FDI sont limitées et il n'existe aucun protocole. Objectifs: Évaluer l'efficacité et l'innocuité du FDI chez les patients atteints d'IRC et vérifier les informations relatives à son utilisation dans les provinces du Canada. Méthodes: Cette étude de cohorte rétrospective comprenait des patients atteints d'IRC sans dialyse (NDD-IRC) et des patients sous dialyse péritonéale (DP) ayant reçu du FDI dans un hôpital de soins tertiaires de la Nouvelle-Écosse entre juin 2020 et mai 2021. Chaque patient a fait l'objet d'un suivi pendant au moins 6 mois. Les résultats d'efficacité étaient les changements par rapport à la base de trois mesures après la première dose de FDI et à 3 et 6 mois, soit l'hémoglobine, la saturation de la transferrine (TSAT) et la ferritine. Les résultats d'innocuité étaient la fréquence et les types de réactions indésirables au FDI. Des sondages ont été envoyés par voie électronique à 33 pharmaciens canadiens spécialisés en néphrologie afin de recueillir des renseignements sur l'utilisation, le dosage, l'administration, la surveillance, le financement et l'innocuité du FDI dans leurs organismes respectifs. Résultats: Au total, 52 perfusions ont été administrées à 35 patients au cours de la période d'étude. Les délais médians entre les doses 1 et 2, et entre les doses 2 et 3 étaient respectivement de 19,1 et 6,6 semaines. Le changement médian entre la base et le premier bilan sanguin de suivi post-FDI était important pour l'hémoglobine (9,0 g/L, p = 0,023), le TSAT (11 points de pourcentage, p < 0,001) et la ferritine (271,4 µg/L, p < 0,001). Les doses médianes de darbépoétine ont diminué par rapport à la base à 6 mois (p < 0,001). Trois effets indésirables se sont produits. Au moins 15 des 23 répondants au sondage (65 %) ont déclaré que le FDI était financé par leur province ou figurait sur les listes de médicaments des hôpitaux. Conclusion: Cette étude fournit des preuves que le FDI est un traitement efficace et sûr de l'anémie chez les patients NDD-IRC et PD.

Systematic review and meta-analysis of intravenous iron-carbohydrate complexes in HFrEF patients with iron deficiency.

Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.