Non-anaemic Iron Deficiency Research Articles

Associations between non-anaemic iron deficiency and outcomes following elective surgery for colorectal cancer: a prospective cohort study.

Iron deficiency is present in up to 75% of patients presenting for colorectal cancer surgery. It is unclear whether iron deficiency without anaemia is associated with worse postoperative outcomes. We hypothesised that, in adults without anaemia undergoing surgery for colorectal cancer, iron deficiency would be associated with worse postoperative outcomes relative to an iron-replete state. We performed a prospective, observational study, recruiting adults (aged ≥ 18 y) without anaemia who were undergoing surgery for colorectal cancer in 16 hospitals across Australia and Aotearoa/New Zealand. Anaemia was defined as a haemoglobin concentration < 130 g.l-1 for men and < 120 g.l-1 for women. Iron deficiency was defined primarily as transferrin saturation < 20%. The primary endpoint was days alive and at home on postoperative day 90. The primary endpoint analysis was adjusted for surgical risk based on recruiting institution; sex; Charlson comorbidity index; CR-POSSUM score; surgical approach; and requirement for neoadjuvant therapy. Of 420 patients, 170 were iron deficient and 250 were iron replete. The median (IQR [range]) days alive and at home in the iron-deficient group was 84.0 (80.7-85.9 [0-88.2]) days and in the iron-replete group was 83.1 (78.7-85.1 [0-88.9]) days. The unadjusted difference in medians between groups was 0.9 (95%CI 0-1.8, p = 0.047) days and the adjusted difference was 0.9 (95%CI 0-1.80, p = 0.042) days, favouring the iron-deficient group. In adult patients without anaemia undergoing surgery for colorectal cancer, iron deficiency defined by transferrin saturation < 20% was not associated with worse patient outcomes and appeared to be associated with more days alive and at home on postoperative day 90.

Prospective study of restless legs syndrome in a blood donors' sample.

Blood donation is suggested to increase the risk of Restless Legs Syndrome (RLS). This study aims to assess the prevalence of RLS in Spanish blood donors and determined its potential correlation with iron metabolism parameters. Prospective cohort study of 129 blood donors (54.3% men, 39.44 years ± 11.0) that underwent a physical examination, blood analysis (hemoglobin, ferritin, transferrin saturation index and soluble transferrin receptor) and a RLS screening questionnaire followed by a prospective follow-up study including a clinical phone interview. A multivariate logistic regression model was performed to examine the association between RLS and other variables. Eighty-four (65.1%) participants were repeat blood donors (mean of 2.11 donations/year) at inclusion and 61 (47.4%) at follow-up (mean of 2.09 donations/year). Non-anemic iron deficiency (ferritin < 50 µg/L) was high in women p < 0.001 and in repeat donors (p = 0.003). The prevalence of RLS was 14.1% at inclusion increasing prospectively (19.5%; p = 0.065). On multivariate analysis, gender was the only variable significantly associated with a RLS diagnosis, being higher in women (OR 5.1; 95% CI 1.71-15.3; p = 0.003). Despite the high prevalence of non-anemic iron deficiency there was no association between ferritin, soluble transferrin receptor concentration values and RLS diagnosis. Gender was associated with RLS diagnosis regardless of other variables.

Iron deficiency among primary school children in Mosul City /Northern Iraq, a cross-section study.

To determine the prevalence of iron deficiency among primary school students in an urban setting. The descriptive, cross-sectional study was conducted from January to April 2019 in Mosul, Iraq, after approval from the ethics review committee of the College of Medicine, Nineveh University, Iraq, and comprised students aged 6-12 years who were part of the 2018-19 academic year at 4 public primary schools located along the two banks of Tigris River. Serum ferritin was measured in all the participants. Data wa analysed using Minitab 20. Of the 827 subjects, 439(53%) were girls and 388(47%) were boys. The overall mean age was 8.5±0.057 years, with 558(67.5%) aged <10 years. The mean serum ferritin level was 8.05±6.43ng/ml, and 173(20.92%) subjects were found to iron-deficient. Among the iron-deficient students, 87(50.29%) had iron deficiency anaemia and 86(49.71%) had non-anaemic iron deficiency. Age and gender were significantly different between students with anaemic and non-anaemic iron deficiency (p<0.05). Within boys, significant difference was also noted in terms of body mass index-for-age values (p<0.05). One-fifth of the students were found to have iron deficiency. Plans to control iron deficiency among young children are essential.

Iron deficiency-related symptoms in non-anemic whole blood donors.

Whole blood donors are at increased risk for iron deficiency (ID). ID anemia is associated with several symptoms, such as fatigue, cognitive dysfunction, pica, and restless leg syndrome (RLS). However, it is unclear if these symptoms also occur when a donor has developed ID without anemia. This study aims to determine whether non-anemic ID (NAID) is associated with the occurrence of ID-related symptoms. We combined data from three studies in whole blood donors (i.e., Donor Insight-III, FIND'EM, and FORTE) to create a substantial sample size (N = 12,143). The self-reported occurrence and severity of ID-related symptoms, such as physical and mental health, fatigue, cognitive functioning, pica, and RLS, was measured using validated questionnaires. Associations were studied using logistic regression modeling with ID-related symptoms derived from the questionnaires as the dependent variable and ferritin level group (0-15 μg/L, 15-30 μg/L, and >30 μg/L) as explanatory variable. After applying inclusion and exclusion criteria, 9829 donors were eligible for analysis. In the models corrected for age, body mass index, Hb level, and cohort, only fatigue was shown to be associated with ferritin levels in men, showing lower odds (OR 1.41, 95% CI 1.11-1.79) for fatigue with higher ferritin levels. In these studies, NAID was only associated with self-reported fatigue in male donors. Although selection bias may have led to underestimated associations, ferritin measurements in donors should be primarily considered as a measure to prevent anemia, rather than to prevent or mitigate NAID-related symptoms.

Ferritin Cutoffs and Diagnosis of Iron Deficiency in Primary Care

Ferritin is often measured by general practitioners, but the association of different cutoffs with the rates of iron deficiency diagnoses, particularly nonanemic iron deficiency, is unknown. To investigate the association of the ferritin cutoff choice with the incidence of nonanemic and anemic iron deficiency diagnoses in primary care. In this retrospective cohort study, patients 18 years or older with at least 1 consultation with a general practitioner participating in the Family Medicine Research Using Electronic Medical Records (FIRE) project, an electronic medical records database of Swiss primary care, from January 1, 2021, to November 30, 2023, were evaluated. Sex, age, clinical patient characteristics, and professional general practitioner characteristics. Incidence of iron deficiency diagnoses (nonanemic and anemic) at ferritin cutoffs of 15, 30, and 45 ng/mL and ferritin testing itself. Time-dependent Cox proportional hazards regression was used to examine associations of patient and general practitioner characteristics with ferritin testing as adjusted hazard ratios (AHRs). The study included 255 351 patients (median [IQR] age, 52 [36-66] years; 52.1% female). Per 1000 patient-years and at ferritin cutoffs of 15, 30, and 45 ng/mL, iron deficiency diagnoses had incidences of 10.9 (95% CI, 10.6-11.2), 29.9 (95% CI, 29.4-30.4), and 48.3 (95% CI, 47.7-48.9) cases, respectively; nonanemic iron deficiency diagnoses had incidences of 4.1 (95% CI, 3.9-4.2), 14.6 (95% CI, 14.3-15.0), and 25.8 (95% CI, 25.3-26.2) cases, respectively; and anemic iron deficiency diagnoses had incidences of 3.5 (95% CI, 3.3-3.7), 6.0 (95% CI, 5.8-6.2), and 7.5 (95% CI, 7.3-7.7) cases, respectively. Ferritin testing showed notable associations with fatigue (AHR, 2.03; 95% CI, 1.95-2.12), anemia (AHR, 1.75; 95% CI, 1.70-1.79), and iron therapy (AHR, 1.50; 95% CI, 1.46-1.54). Ferritin testing was associated with female sex in all age groups, including postmenopausal. Of the patients who received ferritin testing, 72.1% received concomitant hemoglobin testing, and 49.6% received concomitant C-reactive protein testing. In this retrospective cohort study of primary care patients, ferritin cutoffs of 30 and 45 ng/mL were associated with a substantially higher incidence of iron deficiency compared with 15 ng/mL. These results provide a basis for health system-level evaluation and benchmarking of ferritin testing in high-resource settings and call for a harmonization of diagnostic criteria for iron deficiency in primary care.

Nonanemic Iron Deficiency: The Elusive Metrics of Iron in the Human Body

Nonanemic Iron Deficiency: The Elusive Metrics of Iron in the Human Body

Post Covid telogen effluvium: the diagnostic value of serum ferritin biomarker and the preventive value of dietary supplements. a case control study

Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4–12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium.

Nonanemic Iron Deficiency in Cardiac Surgery: A Retrospective Observational Study

Anemia and iron deficiency in patients having cardiac surgery increases their perioperative risk. Nonanemic iron deficiency (NAID) in this group is less well-described. We aimed to investigate the incidence and outcomes of patients with NAID undergoing cardiac surgery. Retrospective observational study. A single, tertiary referral center. Adult patients who were preassessed and underwent cardiac surgery during the study period had data collected. We enrolled 537 patients enrolled and divided them into 4 groups according to hemoglobin and ferritin: NAID, nonanemic iron replete, iron-deficiency anemia (IDA), and non-iron-deficiency anemia. This study was not interventional, but assessed the impact of anemia and iron deficiency on patient outcomes. The primary outcome was the incidence of NAID. Secondary outcomes included the number of patients who became anemic awaiting surgery, allogeneic transfusion burden, length of stay, postoperative complications, and death. 179 of 537 patients (33.3%) had NAID. Seventeen patients (9.5%) became anemic in the NAID group compared with 7 (3.3%) in the nonanemic iron replete group while awaiting for surgery (p = 0.02). Patients with NAID were more likely to receive allogeneic transfusions (33% vs 23%; p = 0.04) and had poorer recovery of hemoglobin at follow-up (13.2 ± 1.46 g/dL vs 13.9 ± 1.46 g/dL; p < 0.001). NAID is common and can lead to progression to anemia and increased transfusion. Iron replacement should be considered in patients with NAID in the preoperative setting. A prospective interventional trial is required to demonstrate the benefit of being iron replete.

High prevalence of iron deficiency and socioeconomic disparities in laboratory screening of non-pregnant females of reproductive age: A retrospective cohort study.

Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly prevalent among non-pregnant females of reproductive age. Canada has no national screening guidelines for this population. Screening, when performed, is often with a complete blood count alone without ferritin or iron indices. The primary objective was to determine the prevalence of screening for NAID and IDA over a 3-year period in non-pregnant females of reproductive age who had tests performed at outpatient laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females ages 15-54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 μg/L, anemia as hemoglobin <120 g/L, and IDA as ferritin <30 μg/L and hemoglobin <120 g/L. Annual household income was estimated using patient postal codes. A total of 784 132 non-pregnant females were included. The 82.1% were screened for iron deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean corpuscular volumes. The median household income was $89454.80 compared with a provincial median of $65285.00. Patients in the lowest income quintile had the highest odds of being anemic, and the lowest odds of having a ferritin checked. A large proportion of non-pregnant females of reproductive age in this cohort were screened for iron deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%. Most patients with IDA did not have microcytosis. Low household income was associated with the greatest odds of anemia and the lowest odds of being screened, highlighting inequitable access to screening for IDA in Ontario, Canada.

Iron deficiency and supplementation in heart failure.

Non-anaemic iron deficiency (NAID) is a strategic target in cardiovascular medicine because of its association with a range of adverse effects in various conditions. Endeavours to tackle NAID in heart failure have yielded mixed results, exposing knowledge gaps in how best to define 'iron deficiency' and the handling of iron therapies by the body. To address these gaps, we harness the latest understanding of the mechanisms of iron homeostasis outside the erythron and integrate clinical and preclinical lines of evidence. The emerging picture is that current definitions of iron deficiency do not assimilate the multiple influences at play in patients with heart failure and, consequently, fail to identify those with a truly unmet need for iron. Additionally, current iron supplementation therapies benefit onlycertain patients with heart failure, reflecting differences in the nature of the unmet need for iron and the modifying effects of anaemia and inflammation on the handling of iron therapies by the body. Building on these insights, we identify untapped opportunities in the management of NAID, including the refinement of current approaches and the development of novel strategies. Lessons learned from NAID in cardiovascular disease could ultimately translate into benefits for patients with other chronic conditions such as chronic kidney disease, chronic obstructive pulmonary disease and cancer.

The effect of anti-inflammatory properties of sumac powder (Rhus coriaria L.) along with ferrous sulfate on blood markers and oxidative stress of young athletic girls with non-anemic iron deficiency (NAID)

The effect of anti-inflammatory properties of sumac powder (Rhus coriaria L.) along with ferrous sulfate on blood markers and oxidative stress of young athletic girls with non-anemic iron deficiency (NAID)

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162.

Time to Resolution of Iron Deficiency: A 10-Year Single State Retrospective Review

Introduction: Iron deficiency can have clinical consequences even without anemia, including fatigue, exercise intolerance and mood disorders. The time from laboratory diagnosis to resolution of iron deficiency has not been previously evaluated. Methods: In a retrospective review of electronic medical record (EMR) data from a single state health system, we identified patients meeting laboratory criteria for iron deficiency (defined as a ferritin level &amp;lt; 25 ng/mL). Patients with at least one follow-up ferritin level of any value within 3 years were included in the final cohort. Patients with a follow-up ferritin &amp;gt; 50 ng/mL at any time point within 3 years were classified as having resolved iron deficiency. Diagnoses of interest included iron deficiency anemia (IDA), as well as other conditions where iron deficiency is routinely assessed and treated irrespective of anemia, namely heart failure (HF) and restless leg syndrome (RLS). Descriptive statistics and time to event analyses (via Cox proportional hazards regression) were performed to determine time to resolution of iron deficiency in the cohort and characteristics predictive of achieving resolution. Results: We identified 13,084 patients with iron deficiency detected between 2010 to 2020. The majority of patients were female (86.6%) and White (79.3%); 57.3% had an EMR diagnosis of IDA (Table 1). We found that 5,485 (41.9%) had resolution of iron deficiency within 3 years of diagnosis, while 7,599 (58.1%) had unresolved iron deficiency. Among those with resolved iron deficiency, the median time to resolution was 1.9 years (IQR 0.8, 3.9 years). Factors associated with resolution of iron deficiency included increasing age (aHR 1.42 [95% CI 1.31 - 1.54], p &amp;lt; 0.001 for age &amp;gt; 60), male gender (1.49 [1.39 - 1.59], p &amp;lt; 0.001) and a diagnosis of HF (1.23 [1.11 - 1.36], p &amp;lt; 0.001) (Table 2). Black race (0.75 [0.68 - 0.83], p &amp;lt; 0.001) and absence of an EMR diagnosis of IDA, HF or RLS (0.75 [0.71 - 0.81], p &amp;lt; 0.001) were associated with a lower likelihood of iron deficiency resolution. Conclusion: Prolonged and unresolved iron deficiency were prevalent in this cohort, with young age, female gender and Black race increasing risk of non-resolution. Interventions are needed to raise awareness of the clinical consequences of non-anemic iron deficiency and of diagnostic ferritin thresholds.

Direct Effect of Iron Deficiency Independent of Anemia on Adverse Perinatal Outcomes- a Scoping Review

Introduction Iron is required throughout pregnancy by both the pregnant individual and the fetus. Iron stores can be depleted during pregnancy resulting in iron deficiency (ID), which is the most common cause of anemia in pregnancy. Iron deficiency anemia (IDA) is associated with an approximately two-fold increase in adverse perinatal outcomes (APO) such as low birth weight (LBW), preterm delivery, and stillbirth. It is uncertain whether depleted iron store in a non-anemic pregnant individual affects fetal growth and well-being. The effect of ID per se on these outcomes, independent of anemia, is the central focus of this scoping review. If an independent association between iron deficiency without anemia (IDWA) and these APO is established and given the potential for non-anemic iron deficiency to progress to IDA, early screening, and intervention before the development of IDA may be important in preventing these morbidities and mortality. Our objective is to determine the current state of existing knowledge concerning IDWA and APO. The specific aims are to determine the prevalence of IDWA in pregnant individuals, assess predictors and determine types of APO associated with IDWA. Methods We performed a comprehensive systematic scoping review of the independent effect of IDWA on APO. The search for relevant studies involved Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Control Register of Controlled Trials, and hand search of citations of relevant articles for cohort and cross-sectional studies, randomized controlled trials, systematic reviews, and meta-analyses, scoping and narrative reviews from the inception of the databases. We used all relevant Medical Subject Headings terms and subheadings with no language restrictions. Two reviewers independently screened titles, abstracts, and full text based on the outlined inclusion and exclusion criteria. The inclusion criteria include relevant studies reporting on IDWA in pregnancy and APO. Exclusion criteria include studies not reporting IDWA and APO, and the presence of medical conditions such as hemoglobinopathies, polycythemia, iron overload, autoimmune and inflammatory conditions. Discrepancies were resolved through discussion and consensus. Covidence ® systematic review software was used for screening, automatically eliminating duplicates and data extraction. PRISMA for Scoping Reviews reporting guidelines was used. The selection process and results of included and excluded studies were presented with a PRISMA flow chart. A narrative summary was conducted to descriptively summarize the findings. Results A total of 4389 articles were identified from the searched databases after all duplicates were removed. Two studies conducted between 2005-2008 and 2017-2018 respectively met the inclusion criteria and were eligible for data extraction. A total of 5684 participants made up of 5479 Danish and 205 Spanish cohorts were included. The prevalence of IDWA in Denmark was 14.2% based on serum ferritin of &amp;lt;30μg/L and hemoglobin ≥110g/L and 20% in Spain using thresholds of SF &amp;lt;12μg/L and Hb≥110g/L. The mean (standard deviation, SD) age of participants was 31.8 ± 5.0 years in Denmark, and the mean (95% CI) was 31.0 (29.4-32.6) years in Spain. In the Danish study, the babies had a mean (SD) birth weight of 3508±523g and were on average 192g smaller (p=0.028). The mean (SD) gestational age (GA) at delivery was 39.8±1.7 weeks, adjusted odds ratio (95%CI) of LBW was 0.6 (0.4-1.0), stillbirth 4.0(1.0-14.3) and gestational diabetes mellitus 1.1 (0.7-1.7) in the IDWA group. The Spanish study reported a mean (95% CI) infant birth weight (IBW) of 3140 (3067-3213) g, reduction in adjusted IBW of -192.4 (-363.6, -21.2)g, p=0.028, R 2c.100 = 35.4, F 194,11 =9.3, p&amp;lt;0.001 in IDWA. Both studies reported the covariates and predictors of APO including parity, race, body mass index, and socioeconomic status. Conclusion Overall, there is limited research on this important obstetric hematology topic. The few available studies identified higher odds of non-causal association between IDWA, stillbirth, and smaller birth weight. Similarly, there was a non-significant causal association with most predictors and maternal medical complications of pregnancy. These findings will motivate further research work by our team. The study will involve the use of large population-based data to establish a potential causal association between IDWA and APO.

Ferritin Reference Ranges in an Adult Population of Working-Age Adults without Anemia

Introduction Considerable controversy has surrounded the creation of reference intervals for ferritin within tested populations. This is particularly true for women and has been attributed to a high prevalence of nonanemic iron deficiency due to physiologic blood loss during menses and physiologic iron transfer during pregnancy. The Quest Blueprint for Wellness (BFW) program is an annual health screening that provides a range of testing to Quest employees and families. Using deidentified data on 24,812 individuals (55% female; age range 18-80 years old) collected as part of this program, we studied the relationship between serum ferritin and characteristics of the study population, red blood cell parameters, and iron saturation in order to better define normal reference ranges for serum ferritin. Methods Test results of participants in the annual BFW screening program conducted between January 2022 and May 2023 were identified (26,535 [53% female]); tests included hematocrit, hemoglobin, RBC indices (including RDW), total serum iron and total iron binding capacity and CRP. Individuals with abnormalities of hemoglobin, hematocrit or RBC indices (including RDW); serum iron or serum TIBC; or elevated CRP were successively excluded, leaving 24,812 participants (55% female). None of these remaining individuals had a personal history of anemia or an identified ICD-10 code associated with anemia or other RBC disorder. This study population was used in subsequent analyses. Multimodal decomposition (MMD) in R (version 4.2.2) was used to calculate reference intervals based on the distribution of results associated with the healthy study subpopulation that was defined. To address the possibility that the TIBC saturation initially employed (20%) was too low, reference intervals were also determined when varying TIBC saturations from 20%-25%. Results As shown in Table 1, the lower limits of the ranges identified did not vary significantly as the TIBC saturation percent was increased from 20% to 25%. The lower limit for women below 50 years of age ranged from 11-13 ng/mL, which was substantially lower than the lower limits for men of the same age. Over the age of 50, the lower limit of the ferritin reference ranges for women increased, approaching but not equaling or exceeding the values observed for men until ages greater than 70. This may reflect the end of menses and the gradual repletion of iron stores. In contrast, the lower limits of the reference ranges for serum ferritin for men increased at ages 30-40 and then declined and fell below that of women in the eighth decade. Conclusions Comparing the lower range of ferritin values between men and women, these data suggest that iron deficiency may be present in a large proportion of working age women in the absence of anemia or abnormal RBC indices. These data also suggest that normal ferritin values are age dependent for both men and women. These conclusions are tempered by the unavailability of a physiologic reference standard able to demonstrate that iron deficiency is in fact present. The lower limit of the ferritin range for women under the age of 60 and for men over the age of 70 approximates the ferritin values associated with the absence of stainable bone marrow iron. While this test is the traditional “gold standard” it is rarely performed for the evaluation of iron status. The evaluation of iron deficiency at present lacks a physiologic indicator, analogous to the relationship between parathyroid hormone and calcium levels which permitted the definition of blood levels of 25 hydroxyvitamin D that represented sufficiency, or methylmalonic acid concentration in B12 deficiency. The broader availability of measures to assess the functional status of reticuloendothelial iron stores available to support erythropoiesis, such as measurements of hepcidin, would facilitate such an assessment.

'Ironing out the risk': Assessing the effect of plateletpheresis donation frequency on iron stores in South-Asian male donors.

Repeated blood donation is a well-known cause of iron deficiency among donors. However, present scientific literature lacks comprehensive evidence regarding the impact of regular plateletpheresis procedures on body iron reserves. In this study, we aimed to detect and correlate iron deficiency (using iron indices) with the frequency of platelet donations. Additionally, we also analysed the correlation between other iron and haematological indices with serum ferritin to determine cost-effective parameters that may serve as an initial screening approach to determine which donors should be subjected to serum ferritin testing. A total of 180 male participants from our platelet donor registry were enrolled in this observational cross-sectional study. Enrolment questionnaires were administered to eligible donors, and biological samples were collected during plateletpheresis donation. Biological tests such as complete blood count, reticulocyte indices, iron indices, vitamin B12 and folate were performed. Donors with ≥12 donations per year showed the highest prevalence of low ferritin (serum ferritin: 15-30 ng/mL) and absent iron stores (serum ferritin <15 ng/mL) (41.3% and 26.7%, respectively). Ferritin showed a significant negative correlation with recent (r = -0.346) and lifetime donations (r = -0.196). The efficacy of other indices for identifying iron depletion was much better using a serum ferritin value <15 ng/mL. Regular plateletpheresis donations can lead to varying severities of non-anaemic iron deficiency. Blood centres must regularly monitor frequent plateletpheresis donors (especially donors with more than 11 donations in a calendar year) and ideally maintain their serum ferritin above 30 ng/mL.

Iron deficiency in young basketball players: Is a 100 μg/L ferritin cut-off appropriate for iron supplementation?: Results of a randomized placebo-controlled study.

Iron deficiency (ID) is one of the most common factors that may reduce sports performance, supplementation forms and doses are still not standardized in athletes. Our aim was to assess the iron status of young male basketball players and to study the effect of iron supplementation in a randomized placebo-controlled study. We hypothesized that due to the higher iron demand of athletes, the 100 μg/L ferritin cut-off may be appropriate to determine the non-anemic ID. During a sports cardiology screening, questionnaires, laboratory tests, electrocardiograms, echocardiography exams, and cardiopulmonary exercise tests were performed. Athletes with ID (ferritin <100 μg/L) were randomized into iron and placebo groups. Ferrous sulfate (containing 100 mg elemental iron [II] and 60 mg ascorbic acid) or placebo (50 mg vitamin C) was administered for 3 months. All exams were repeated after the supplementation period. We included 65 (age 15.8 ± 1.7 years) basketball players divided into four age groups. Non-anemic ID was observed in 60 (92%) athletes. After supplementation, ferritin levels were higher in the iron group (75.5 ± 25.9 vs. 54.9 ± 10.4 μg/L, p < .01). Ferritin >100 μg/L level was achieved only in 15% of the athletes. There were no differences in performance between the groups (VO2 max: 53.6 ± 4.3 vs. 54.4 ± 5.7 mL/kg/min, p = .46; peak lactate: 9.1 ± 2.2 vs. 9.1 ± 2.6 mmol/L, p = .90). As a result of the 3-month iron supplementation, the ferritin levels increased; however, only a small portion of the athletes achieved the target ferritin level, while performance improvement was not detectable.

Nitrosative and Oxidative Stress, Reduced Antioxidant Capacity, and Fiber Type Switch in Iron-Deficient COPD Patients: Analysis of Muscle and Systemic Compartments

We hypothesized that a rise in the levels of oxidative/nitrosative stress markers and a decline in antioxidants might take place in systemic and muscle compartments of chronic obstructive pulmonary disease (COPD) patients with non-anemic iron deficiency. In COPD patients with/without iron depletion (n = 20/group), markers of oxidative/nitrosative stress and antioxidants were determined in blood and vastus lateralis (biopsies, muscle fiber phenotype). Iron metabolism, exercise, and limb muscle strength were assessed in all patients. In iron-deficient COPD compared to non-iron deficient patients, oxidative (lipofuscin) and nitrosative stress levels were greater in muscle and blood compartments and proportions of fast-twitch fibers, whereas levels of mitochondrial superoxide dismutase (SOD) and Trolox equivalent antioxidant capacity (TEAC) decreased. In severe COPD, nitrosative stress and reduced antioxidant capacity were demonstrated in vastus lateralis and systemic compartments of iron-deficient patients. The slow- to fast-twitch muscle fiber switch towards a less resistant phenotype was significantly more prominent in muscles of these patients. Iron deficiency is associated with a specific pattern of nitrosative and oxidative stress and reduced antioxidant capacity in severe COPD irrespective of quadriceps muscle function. In clinical settings, parameters of iron metabolism and content should be routinely quantify given its implications in redox balance and exercise tolerance.

Iron Deficiency and Anemia in Male and Female Adolescent Athletes Who Engage in Ball Games.

The aim of this study was to assess the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) among male adolescent athletes who participate in non-calorie-restricting sports, and to compare the results with female athletes of the same age and sports. Data of the hemoglobin concentration (Hb) and serum ferritin (sFer) levels of male (n = 350) and female (n = 126) basketball and football players, aged 11-18, from two sport medicine centers in Israel were gathered and analyzed. Mild ID was defined as sFer ≤ 30 µg/L, moderate as sFer ≤ 20 µg/L, and severe as sFer ≤ 10 µg/L. IDA was defined as sFer ≤ 20 µg/L and Hb < 13 g/dL for males and sFer ≤ 20 µg/L and Hb < 12 g/dL for females. The prevalence of mild ID was 41.1% and 53.2%, moderate was 17.4% and 27.8%, and severe was 2% and 4.8% in males and females, respectively. The prevalence of IDA was 2.6% in males and 4% in females. Mild and moderate ID was significantly higher among females. In conclusion, non-anemic ID, which is known to be common among female athletes, especially in sports requiring leanness, is also highly prevalent among adolescent males playing ball games. Therefore, screening for hemoglobin and sFer is recommended for young athletes of both genders and in all sports.

Ferritin screening and Iron treatment for maternal anemia and fetal growth restriction prevention - A multicenter randomized controlled trial (FAIR Study).

Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks' gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee.