<b>Introduction:</b> The prevalence of preoperative anemia is the highest in the group of colorectal cancer (CRC) patients and may reach over 75%. The prevalence of anemia in CRC patients increases even further following surgery. Approximately 75-80% of anemic CRC patients present with absolute or functional iron deficiency (ID). Preoperative anemia constitutes an independent risk factor for allogeneic blood transfusion (ABT), postoperative complications, prolonged length of hospital stay, and increased mortality. ABT is itself associated with increased morbidity and mortality.<b>Aim:</b> The aim of this review article was to present the pathophysiology and the current approach to the diagnostics and treatment of preoperative iron deficiency anemia (IDA) in CRC patients.<b>Material and methods:</b> Extensive search of medical literature databases was performed (Pubmed, Embase). The key words that were used were as follows: CRC, colorectal surgery, ID, IDA, intravenous iron, Patient Blood Management (PBM).<b>Results:</b> There are several laboratory parameters that can be used for IDA diagnosis, however, the simplest and most cost- -effective is reticulocyte hemoglobin equivalent (RET-He). Pathophysiologic features of IDA in CRC patients favor treatment with intravenous, as opposed to oral, iron formulations. Applying PBM strategies minimizes the exposure to ABT.<b>Conclusions:</b> Preoperative IDA is highly prevalent among CRC patients. Preoperative anemia is an independent risk factor for ABT, increased morbidity and mortality, as well as prolonged hospital length of stay. The same negative consequences are associated with ABT. Therefore, preoperative IDA in CRC patients needs to be screened for, diagnosed, and treated before surgery. Effective treatment of preoperative IDA in CRC patients is with intravenous iron formulations. ABT should be the treatment of last resort due to the risk of negative clinical consequences, including an increased rate of cancer recurrence.

BACKGROUND: The complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States.
METHODS: Iron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t½]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®.
RESULTS: Iron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t½: 15 h versus 40.3 h); t½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®.
CONCLUSIONS: Simple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars.

BACKGROUND: Iron deficiency anaemia is common among pregnant women in Nigeria. The standard treatment is oral iron therapy, which can be sub-optimal due to side effects. Intravenous ferric carboxymaltose (FCM) is an evidenced-based alternative treatment with a more favourable side effect profile requiring administration according to a standardized protocol. In this study, we assessed the fidelity of administering a single dose of FCM according to protocol and identified factors influencing implementation fidelity.
METHODS: We used a mixed-method approach with a sequential explanatory design nested in a clinical trial across 11 facilities in Lagos and Kano States, Nigeria. Guided by a conceptual framework of implementation fidelity, we quantitatively assessed adherence to protocol by directly observing every alternate FCM administration, using an intervention procedure checklist, and compared median adherence by facility and state. Qualitative fidelity assessment was conducted via in-depth interviews with 14 skilled health personnel (SHP) from nine purposively selected health facilities, using a semi-structured interview guide. We analyzed quantitative data using descriptive and inferential statistics in Stata and used thematic analysis to analyze the transcribed interviews in NVivo.
RESULTS: A total of 254 FCM administrations were observed across the 11 study sites, with the majority in secondary (63%), followed by primary healthcare facilities (PHCs) (30%). Overall, adherence to FCM administration as per protocol was moderate (63%) and varied depending on facility level. The lowest level of adherence was observed in PHCs (36%). Median, adherence level showed significant differences by facility level (p = 0.001) but not by state (p = 0.889). Teamwork and availability of protocols are facilitation strategies that contributed to high fidelity. However, institutional/ logistical barriers are contextual factors that influenced the varied fidelity levels observed in some facilities.
CONCLUSIONS: Collaborative teams and access to operating protocols resulted in high fidelity in some facilities. However, in some PHCs, fidelity to FCM was low due to contextual factors and intervention complexities, thereby influencing the quality of delivery. In Nigeria, scale-up of FCM will require attention to staff strength, teamwork and availability of administration protocols, in order to optimize its impact on anaemia in pregnancy.

BACKGROUND: Patient blood management recommends the use of intravenous (IV) iron infusion to reduce inappropriate blood transfusion perioperatively for anaemic surgical patients. However, evidence regarding its use in urgent femoral fracture surgery is limited. This systematic review aims to collate the current evidence regarding the utilisation of IV iron in femoral fracture surgery.
METHODS: MEDLINE, Embase, Cochrane CENTRAL, Clinicaltrials.gov, and the WHO ICTRP databases were systematically searched for randomised controlled trials (RCT) comparing the outcomes of perioperative IV iron infusion with placebo in adults requiring surgical management for femoral fractures. Risk ratios (RR) were calculated using the Mantel-Haenszel method for dichotomous outcomes, and mean differences (MD) were calculated with the inverse-variance method for continuous outcomes.
RESULTS: Six RCTs with 1292 patients were included. No statistically significant difference was found in the proportion of patients receiving red blood cell (RBC) transfusion (RR = 0.87, 95%CI: 0.75; 1.01, p = 0.058) between groups. Statistically significant difference in postoperative haemoglobin concentration was found between groups measured between day 4-7 of admission (MD = 1.93 g/L, 95%CI: 0.48; 3.39, p = 0.024), but not clinically significant. No statistically significant differences were found between groups in mortality rate, length of hospital stay, infection rate, or return to home rate.
CONCLUSIONS: Current evidence indicates that IV iron infusion alone does not provide any clinically significant benefit in femoral fracture surgery. Further high-quality RCTs are needed to explore its synergistic potential when used in combination with other perioperative optimisation methods, including tranexamic acid, erythropoietin and cell salvage.

Iron deficiency (ID) is present in approximately 50% of patients with heart failure (HF) and even higher prevalence rate up to 80% in post-acute HF setting. The current guidelines for HF recommend intravenous (IV) iron replacement in HF with reduced or mildly reduced ejection fraction and ID based on clinical trials showing improvements in quality of life and exercise capacity, and an overall treatment benefit for recurrent HF hospitalization. However, several barriers cause challenges in implementing IV iron supplementation in practice due, in part, to clinician knowledge gaps and limited resource availability to protocolize routine utilization in appropriate patients. Thus, the current review will discuss practical considerations in ID treatment, implementation of evidence-based ID treatment to improve regional health disparities with toolkits, inclusion/exclusion criteria of IV iron supplementation, and clinical controversies in ID treatment, as well as gaps in evidence and questions to be answered.

BACKGROUND: Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron.
METHODS: In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels.
RESULTS: Two hundred nine patients were randomized to FC and had a day 1 dosing visit (n = 103) or SOC (n = 106). The two groups had similar baseline laboratory characteristics; however, atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was -30.8 μg (FC vs. SOC; p = 0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of -37.2 mg (p = 0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC versus SOC. Serious adverse events occurred in 28% of patients receiving FC versus 37% in those receiving SOC.
CONCLUSIONS: In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

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.

Iron deficiency and heart failure frequently co-occur, sparking clinical research into the role of iron repletion in this condition over the last 20 years. Although early nonrandomized studies and subsequent moderate-sized randomized controlled trials showed an improvement in symptoms and functional metrics with the use of intravenous iron, 3 recent larger trials powered to detect a difference in hard cardiovascular outcomes failed to meet their primary endpoints. Additionally, there are potential concerns related to side effects from intravenous iron, both in the short and long term. This review discusses the basics of iron biology and regulation, the diagnostic criteria for iron deficiency and the clinical evidence for intravenous iron in heart failure, safety concerns, and alternative therapies. We also make practical suggestions for the management of patients with iron deficiency and heart failure and outline key areas in need of future research.

BACKGROUND: 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).
CONCLUSIONS: 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.