Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

BACKGROUND: NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. METHODS: A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. RESULTS: A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). CONCLUSIONS: Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

The effect of UNIMMAP multiple micronutrient supplements versus iron-folic acid and placebo in anemia reduction among women of reproductive age in Kebribeyah Woreda, Somali Regional State, Ethiopia: a study protocol for a community-based individual RCT.

BACKGROUND: Women of reproductive age (WRA) in developing countries are often at risk of micronutrient deficiencies due to inadequate intakes and excessive losses. OBJECTIVE: The purpose of this trial is to assess the effectiveness of United Nations International Multiple Micronutrient Antenatal Preparation-Multiple Micronutrient Supplements (UNIMMAP-MMS) versus iron-folic acid (IFA) among WRA in reducing anemia. METHODS: Three parallel groups of WRA will participate in a community-based, individually randomized, double-blinded, placebo-controlled superiority trial. After consent, the sample of 375 mildly or moderately anemic women based on hemoglobin by Hemocue will be randomly assigned across two interventions and one control arm. Trial participants in intervention arms will receive UNIMMAP-MMS or IFA while those in the control arm will receive placebos twice a week for 17 weeks. The primary outcome will be a change in mean hemoglobin (Hb) concentrations. Outcome assessors and study participants will be blinded to the type of supplements and study arm. DISCUSSION: The World Health Organization (WHO) added UNIMMAP-MMS to its essential medicine lists in 2021 but recommended rigorous study. Several factors in addition to inadequate intakes of iron and folic acid contribute to the high prevalence of anemia among WRA in the Somali region. The findings of this study will provide evidence on the effect of UNIMMAP-MMS and IFA on Hb concentrations and anemia prevalence among anemic WRA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05682261. Registered on January 12, 2023.

Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

Iron Deficiency Anemia: An Updated Review.

BACKGROUND: Worldwide, iron deficiency anemia is the most prevalent nutritional deficiency disorder and the leading cause of anemia in children, especially in developing countries. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even following the correction of iron deficiency anemia. OBJECTIVE: This article aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, prevention, and management of children with iron deficiency anemia. METHODS: A PubMed search was conducted in February 2023 in Clinical Queries using the key term "iron deficiency anemia". The search strategy included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies (including case reports and case series), and reviews (including narrative reviews, clinical guidelines, and meta-analyses) published within the past 10 years. Google, UpToDate, and Wikipedia were also searched to enrich the review. Only papers published in the English literature were included in this review. The information retrieved from the search was used in the compilation of the present article. RESULTS: Iron deficiency anemia is most common among children aged nine months to three years and during adolescence. Iron deficiency anemia can result from increased demand for iron, inadequate iron intake, decreased iron absorption (malabsorption), increased blood loss, and rarely, defective plasma iron transport. Most children with mild iron deficiency anemia are asymptomatic. Pallor is the most frequent presenting feature. In mild to moderate iron deficiency anemia, poor appetite, fatigability, lassitude, lethargy, exercise intolerance, irritability, and dizziness may be seen. In severe iron deficiency anemia, tachycardia, shortness of breath, diaphoresis, and poor capillary refilling may occur. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even with the correction of iron deficiency anemia. A low hemoglobin and a peripheral blood film showing hypochromia, microcytosis, and marked anisocytosis, should arouse suspicion of iron deficiency anemia. A low serum ferritin level may confirm the diagnosis. Oral iron therapy is the first-line treatment for iron deficiency anemia. This can be achieved by oral administration of one of the ferrous preparations, which is the most cost-effective medication for the treatment of iron deficiency anemia. The optimal response can be achieved with a dosage of 3 to 6 mg/kg of elemental iron per day. Parenteral iron therapy or red blood cell transfusion is usually not necessary. CONCLUSION: In spite of a decline in prevalence, iron deficiency anemia remains a common cause of anemia in young children and adolescents, especially in developing countries; hence, its prevention is important. Primary prevention can be achieved by supplementary iron or iron fortification of staple foods. The importance of dietary counseling and nutritional education cannot be overemphasized. Secondary prevention involves screening for, diagnosing, and treating iron deficiency anemia. The American Academy of Pediatrics recommends universal laboratory screening for iron deficiency anemia at approximately one year of age for healthy children. Assessment of risk factors associated with iron deficiency anemia should be performed at this time. Selective laboratory screening should be performed at any age when risk factors for iron deficiency anemia have been identified.

[Consensus on the clinical diagnosis, treatment, and prevention of cancer related anemia in China (2023 edition)].

Cancer related anemia (CRA) is a common side effect in patients with tumors, the incidence of which is related to tumor type, treatment regimen, the duration of chemotherapy, etc. The pathogenesis of CRA has not been fully defined. CRA may lead to chemotherapy dose reduction or may even delay chemotherapy. Patients with CRA require red blood cell transfusion, thus increasing the treatment cost, reducing the efficiency of chemotherapy and the patient's quality of life, and shortening the survival time. The main treatments of CRA include red blood cell transfusion, iron supplements, erythropoietin, and so on. Based on recent literature and clinical studies, the expert committee of the China Anti-Cancer Association drew up the consensus on the diagnosis and treatment of anemia related to tumor in China (2023 edition). The 2023 consensus incorporates the latest evidence-based medicine evidence and Traditional Chinese Medicine related content and aims to provide more reliable diagnosis and treatment plans for Chinese oncologists to help improve CRA and the quality of life in patients with cancer.

Bionics investigation of blood 25-hydroxyvitamin D in the interpretable biomechanics diagnosis of childhood anemia.

Vitamin D deficiency (VDD) causes a wide range of health problems, including anemia in infants. If not treated promptly, it may create serious issues for infants with long-term impacts. Therefore, a satisfactory solution to this problem is required. This investigation was to explore the correlation between the blood 25-hydroxyvitamin D (25(OH)D) levels and childhood anemia. In this investigation, a cross-sectional examination was performed on 2,942 babies ranging in age from 2 to 36 months and classified into three cohorts: VDD (Vitamin D deficiency), VDI (Vitamin D insufficiency), and VDS (Vitamin D sufficiency). Multiple-variables and multinomially-related logistic regressions for examining the anemia status-vitamin D (Vit-D) relationship of the baseline as the interpretable visual quality models were examined. The median serum 25(OH)D level in 2,942 infants was 24.72±4.26 ng/l, with 661 cases (22.5%) of VDD and 1710 cases of deficiency (58.1%), and a noticeable seasonal variation (p<0.05). Anemia was present in 28.5% of the VDD group compared with 3.3% in vit-D sufficient infants (p<0.0001). Lower levels of 25(OH)D were found to be associated with an increased risk of anemia in a multiple-variable regression analysis. In healthy children, low 25(OH)D levels were associated with increased risk of anemia. Biologically inspired, primary care physicians should assess Vit-D levels and place a greater emphasis on adequate supplementation for deficiency prevention.

Haemoglobin diagnostic cut-offs for anaemia in Indian women of reproductive age.

BACKGROUND: The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia. METHOD: A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation. RESULTS: The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL). CONCLUSION: The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia.

Anemia: Evaluation of Suspected Anemia.

Anemia is a common condition encountered in inpatient and outpatient primary care settings. When anemia is detected, it is essential to investigate the cause to provide appropriate treatment. Patients may present with symptomatic anemia (eg, fatigue, weakness, shortness of breath), or anemia may be an incidental finding on laboratory evaluation. Initial evaluation consists of a thorough history and physical examination and a complete blood cell count (CBC). Careful examination of the CBC and the mean corpuscular volume provides important clues to the classification and cause of anemia. Supplemental tests may include a peripheral blood smear; reticulocyte count; iron panel (ie, ferritin and iron levels, total iron-binding capacity, transferrin saturation); and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin.

Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

Anemia of inflammatory: does eiderr knowledge mean better diagnosis and treatment?

Anemia, which is a manifestation of the deterioration of patients' health and performance, is a common concomitant condition in diseases with signs of inflammation activation. This anemia - anemia of inflammation, is caused by disturbances of iron metabolism that lead to iron retention within macrophages, cytokine mediated inhibition of erythropoietin function and erythroid progenitor cell differentiation, and a reduced erytrocyte half-life. Anemia is usually mild to moderate, normocytic and normochromic. It is characterized by low iron circulation, but normal to increased levels of stored ferritin and the hormone hepcidin. The primary therapeutic approach is the treatment of the underlying inflammatory disease. In case of failure, iron supplementation and / or treatment with erythropoietin stimulating agents may be used. Blood transfusions are just an emergency treatment for life-threatening anemia. A new treatment modalities with hepcidin-modifying strategies and stabilizers of hypoxia inducible factors is emerging. However, their therapeutic efficacy needs to be verified and evaluated in clinical trials.

[Anemia: Diagnostics and Therapy]. / Ambulante Anämiediagnostik und -therapie.

The most common cause of anemia is iron deficiency, followed by anemia of chronic disease, which is due to an inflammatory reaction in chronic diseases such as heart failure, renal failure, rheumatoid diseases and cancer. Also from the therapeutic point of view, it is useful to divide iron deficiency anemia into two forms: absolute and functional iron deficiency. Absolute iron deficiency is characterized by low iron stores and low total iron. In functional iron deficiency, a sufficient amount of storage iron is present, but it cannot be mobilized. Therapy of iron deficient anemia should always eliminate the underlying cause. The goal of therapy is sustained normalization of hemoglobin concentration and total body iron. Therapy for absolute iron deficiency focuses on improving iron stores, eliminating chronic blood losses, and optimizing iron absorption via an iron-rich diet and iron supplementation. In the case of functional iron deficiency with inflammation present, IV iron supplementation is recommended in certain situations in addition to treatment of the underlying disease, especially in patients with cancer.

Anaemia in patients with self-reported use of iron supplements in the BAriatric surgery SUbstitution and nutrition study: A prospective cohort study.

BACKGROUND AND AIMS: After bariatric surgery, micronutrient deficiencies may lead to anaemia. To prevent post-operative deficiencies, patients are recommended lifelong micronutrient supplementation. Studies investigating the effectiveness of supplementation to prevent anaemia after bariatric surgery are scarce. This study aimed to investigate the relationship between nutritional deficiencies and anaemia in patients who report use of supplementation two years after bariatric surgery versus patients who do not. METHODS AND RESULTS: Obese (BMI≥35 kg/m2) individuals (n = 971) were recruited at Sahlgrenska University Hospital in Gothenburg, Sweden between 2015 and 2017. The interventions were Roux-en-Y gastric bypass (RYGB), n = 382, sleeve gastrectomy (SG), n = 201, or medical treatment (MT), n = 388. Blood samples and self-reported data on supplements were collected at baseline and two years post treatment. Anaemia was defined as haemoglobin <120 g/L for females and <130 g/L for males. Standard statistical methods, including a logistic regression model and a machine learning algorithm, were used to analyse data. The frequency of anaemia increased from baseline in patients treated with RYGB (3·0% vs 10·5%; p < 0·05). Neither iron-dependent biochemistry nor frequency of anaemia differed between participants who reported use of iron supplements and those who did not at the two-year follow-up. Low preoperative level of haemoglobin and high postoperative percent excessive BMI loss increased the predicted probability of anaemia two years after surgery. CONCLUSION: The results from this study indicate that iron deficiency or anaemia may not be prevented by substitutional treatment per current guidelines after bariatric surgery and highlights there is reason to ensure adequate preoperative micronutrient levels. TRIAL REGISTRATION: March 03, 2015; NCT03152617.

Current concepts in preoperative anemia management in obstetrics.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of currently recommended treatment approaches for anemia during pregnancy, with a special focus on iron deficiency and iron deficiency anemia (IDA). RECENT FINDINGS: As consistent patient blood management (PBM) guidelines in obstetrics are still lacking, recommendations regarding the timing of anemia screening and the treatment recommendations for iron deficiency and IDA during pregnancy are still controversial. Based on increasing evidence, early screening for anemia and iron deficiency should be recommended at the beginning of each pregnancy. To reduce maternal and fetal burden, any iron deficiency, even without anemia, should be treated as early as possible during pregnancy. While oral iron supplements administered every other day are the standard treatment in the first trimester, the use of intravenous iron supplements is increasingly suggested from the second trimester onwards. SUMMARY: The treatment of anemia, and more specifically iron deficiency anemia during pregnancy, holds many possibilities for improvement. The fact that the period of risk is known well in advance and thus there is a long optimization phase is per se an ideal prerequisite for the best possible therapy of treatable causes of anemia. Standardization of recommendations and guidelines for screening and treatment of IDA in obstetrics is required for the future. In any case, a multidisciplinary consent is the precondition for a successfully implementation of anemia management in obstetrics to establish an approved algorithm easily enabling detection and treatment of IDA during pregnancy.

Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa.

BACKGROUND: Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB. RESULTS: Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted. CONCLUSIONS: The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80-100 g/L (8-10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.

Anemia after kidney transplantation.

Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence estimated between 20 and 80% depending on how defined. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA (within the first 6 months after transplantation) and impaired glomerular filtration rate (GFR) commonly responsible for late PTA (after 6 months). Medications, viral infections, chronic inflammation, and comorbidities also play a role. PTA has relevant long-term consequences and is a potential risk factor for allograft dysfunction, cardiovascular morbidity, and mortality. Thus, an anemia evaluation, approximately 3 months post-transplantation, is recommended in order to start early treatment and improve prognosis. Iron status, vitamin B12, folate, markers of hemolysis, and viral PCR should be checked, and medications, in particular combinations of medications, should be carefully evaluated. PTA treatment may be challenging and should be directed to the underlying causes. Iron supplementation and erythropoietin therapy, not extensively used in KTR, may be indicated. Every effort should be made to avoid blood transfusions in the pre-transplant period to avoid allosensitization. Anemia should be corrected to prepare candidates for kidney transplantation in order to reduce the need for perioperative blood transfusions as well.

Treatment Strategies in Anemic Patients Before Cardiac Surgery.

Both preoperative anemia and the transfusion of red blood cells have been associated with increased morbidity and mortality after cardiac surgery. To reduce the need for blood transfusion during surgery and improve patient outcomes, patient blood management programs have been developed. A primary focus of patient blood management in the preoperative period is the identification, diagnosis, and treatment of preoperative anemia, as anemia is associated with an increased risk of preoperative blood transfusion. In this narrative review, the authors focus on the laboratory screening of anemia before surgery and the evidence and limitations of different treatment strategies in anemic patients scheduled for cardiac surgery. To accurately correct preoperative anemia, the timely detection and definition of the etiology of anemia before elective cardiac surgery are crucial. Multiple randomized studies have been performed using preoperative iron supplementation and/or administration of erythropoiesis-stimulating agents in patients undergoing cardiac surgery. Although preoperative iron substitution in patients with iron deficiency is recommended, the evidence of its effectiveness is limited. In patients with nonpure iron deficiency anemia, combined therapy with erythropoiesis-stimulating agents and intravenous iron is recommended. Combined therapy might effectively reduce the need for red blood cell transfusion, even if applied shortly before cardiac surgery. The therapeutic effect on morbidity and mortality remains unclear. Nonetheless, the timely preoperative assessment of anemia and determination of iron status, eventually leading to targeted therapy, should become a standard of care and might potentially improve patient outcomes.

Comparative analysis of oral and intravenous iron therapy in rat models of inflammatory anemia and iron deficiency.

Anemia is a major health issue and associated with increased morbidity. Iron deficiency anemia (IDA) is the most prevalent, followed by anemia of chronic disease (ACD). IDA and ACD often co-exist, challenging diagnosis and treatment. While iron supplementation is the first-line therapy for IDA, its optimal route of administration and the efficacy of different repletion strategies in ACD are elusive. Female Lewis rats were injected with group A streptococcal peptidoglycan-polysaccharide (PG-APS) to induce inflammatory arthritis with associated ACD and/or repeatedly phlebotomized and fed with a low iron diet to induce IDA, or a combination thereof (ACD/IDA). Iron was either supplemented by daily oral gavage of ferric maltol or by weekly intravenous (i.v.) injection of ferric carboxymaltose for up to 4 weeks. While both strategies reversed IDA, they remained ineffective to improve hemoglobin (Hb) levels in ACD, although oral iron showed slight amelioration of various erythropoiesis-associated parameters. In contrast, both iron treatments significantly increased Hb in ACD/IDA. In ACD and ACD/IDA animals, i.v. iron administration resulted in iron trapping in liver and splenic macrophages, induction of ferritin expression and increased circulating levels of the iron hormone hepcidin and the inflammatory cytokine interleukin-6, while oral iron supplementation reduced interleukin-6 levels. Thus, oral and i.v. iron resulted in divergent effects on systemic and tissue iron homeostasis and inflammation. Our results indicate that both iron supplements improve Hb in ACD/IDA, but are ineffective in ACD with pronounced inflammation, and that under the latter condition, i.v. iron is trapped in macrophages and may enhance inflammation.