Ferritin Cutoff Research Articles

A-159 Re-evaluating Ferritin Cutoffs for the Diagnosis of Iron Deficiency and Iron Deficiency Anemia

Abstract Background Iron deficiency (ID) is the most common nutrient deficiency in the world and iron deficiency anemia (IDA) is estimated to affect 1.24 billion people. Serum ferritin is an iron storage protein commonly used as a biomarker for ID and IDA. The ferritin lower limit of normal (LLN) defined in many clinical laboratories is lower than evidence-based cutoffs and may not detect ID and IDA with adequate sensitivity, particularly when sex-based reference intervals (RIs) are used. This may be due in part to the use of asymptomatic, iron-depleted individuals for RI studies. Recent efforts have been made to increase the LLN for ferritin to at least 30 ng/mL and re-evaluate sex based RIs to improve diagnosis of ID and IDA. In this study, we aimed to investigate LLN ferritin cutoffs for ID and IDA in our patient population. Methods Patient data from June 2022-May 2023 were collected with approval from the Institutional Review Board (IRB), including age, sex, and values for ferritin, iron, transferrin saturation, and hemoglobin. Patients were classified as iron replete (IR), ID, or IDA based on measurements for iron, transferrin saturation, and hemoglobin. IR patients were defined as having iron and transferrin saturation values within current RIs, while those below the cutoff were grouped as ID. ID and IDA were further classified based on hemoglobin values. A range of ferritin concentrations between 1 and 100 ng/mL were used to calculate true and false positive rates (TPR and FPR) and diagnostic accuracy (DA). Receiver operator characteristic (ROC) curve and J index analysis were used to define optimal ferritin cutoffs for ID and IDA. Results Data from 26,455 patients (65% female) were used in this study. Conclusions These findings highlight the need to re-examine ferritin RIs in the context of ID/IDA, especially for those patients assigned female at birth.

Association between Adiposity and Iron Status in Women of Reproductive Age: Data from the UK National Diet and Nutrition Survey (NDNS) 2008–2019

BackgroundOverweight/obesity and iron deficiency (ID) are highly prevalent in women of reproductive age (WRA), impacting on women’s health. Obesity is a risk factor for nutritional deficiencies but its association with ID is unclear. ObjectivesTo determine the association between adiposity and markers of iron status and ID prevalence in WRA. MethodsThis cross-sectional study analyzed the National Diet and Nutrition Survey (2008–2019) data, focusing on women aged 18–49 y with body mass index (BMI) ≥18.5 kg/m2. Prevalence of anemia, iron deficiency anemia (IDA), and ID were analyzed. Ferritin was adjusted for C-reactive protein. Iron status was assessed across high and low BMI, waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR). χ2, linear and logistic regressions were performed adjusting for covariates. ResultsAmong 1098 WRA, 496 normal weight and 602 overweight/obesity, prevalence rates were: anemia 9.2% and IDA 6.8%. Anemia was more prevalent in those with higher WHtR and WHR (11.9% compared with 5.9% and 16.7% compared with 6.5%, both P < 0.001). WRA with increased WC, WHtR, and WHR had higher IDA prevalence than those with lower adiposity (8.5% compared with 4.3%, P = 0.005; 9.4% compared with 3.3%, P < 0.001; 12.1% compared with 4.9%, P < 0.001). ID prevalence was 49.7% (ferritin cutoff 30 μg/L) and 19.6% (ferritin cutoff 15 μg/L), showing similar rates across adiposity groups. ID prevalence defined by soluble transferrin receptor (sTfR) was higher in women with increased WHR (P = 0.001). Higher WHR predicted ID categorized by sTfR (adjusted odds ratio [aOR]: 2.104, P = 0.004), and WHtR and WHR predicted anemia and IDA (anemia: WHtR aOR: 2.006, P = 0.036; WHR aOR: 4.489, P < 0.001 and IDA: WHtR aOR: 2.942, P = 0.012; WHR aOR: 4.142, P < 0.001). ConclusionsAt least 1 in 5 WRA in the UK are iron deficient, highlighting the need to revise current policies. Greater central adiposity was strongly associated with impaired iron status and the development of anemia, IDA, and ID.

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.

An audit of the iron status of patients at Chris Hani Baragwanath Academic Hospital, in Johannesburg, South Africa.

Iron deficiency is a common disorder, especially in developing countries. Accurately assessing iron status remains challenging, particularly for patients with chronic diseases such as HIV and chronic kidney disease, prevalent in South Africa. This study aimed to determine how ferritin cut-offs affect iron status classification in adult patients treated at a tertiary hospital in South Africa. Additionally, it assessed the frequency of these conditions and the impact of age and gender on iron status. This retrospective study analysed iron profiles in adult patients from 01 October 2020 to 31 March 2021. Iron status was categorised into five groups: iron deficiency anaemia (IDA), anaemia of chronic disease, IDA with anaemia of chronic disease, iron deficiency without anaemia, and iron replete based on haemoglobin, transferrin saturation, and ferritin levels. The impact of using two different ferritin cut-off values (15 µg/L and 30 µg/L) was investigated. The study included 3221 complete iron profiles. There was a predominance of female patients (2.2:1 ratio). Anaemia of chronic disease was the most prevalent iron disorder (39%), regardless of ferritin cut-off. Using a higher ferritin cut-off of 30 µg/L significantly increased the detection rates of both IDA and iron deficiency without anaemia (p < 0.001). This study suggests that a higher ferritin threshold (30 µg/L) might improve diagnosis of iron disorders in settings with high inflammatory diseases. Further studies are needed to refine thresholds. Local guidelines should be adjusted to consider higher ferritin cut-offs, and longitudinal studies are recommended to evaluate long-term outcomes. This study confirms the use of higher ferritin cut-offs for enhanced detection of iron deficiency states. The findings also emphasise the ongoing need for establishing simple, standardised, and accurate methods for iron status classification.

Sex, lies, and iron deficiency: a call to change ferritin reference ranges.

Iron deficiency is a very common and treatable disorder. Of all the tests available to diagnose iron deficiency, the serum ferritin is the most able to discriminate iron deficiency from other disorders. However, the reference range for ferritin in many laboratories will lead to underdiagnosis of iron deficiency in women. Studies have shown that 30%-50% of healthy women will have no marrow iron stores, so basing ferritin cutoffs on the lowest 2.5% of sampled ferritins is not appropriate. In addition, several lines of evidence suggest the body physiologic ferritin "cutoff" is 50 ng/mL. Work is needed to establish more realistic ferritin ranges to avoid underdiagnosing a readily treatable disorder.

Serum Ferritin Levels Prior to Mobilization and Collection May Not Influence Stem Cell Yield

Background Bone marrow transplantation requires collecting an adequate number of hematopoietic stem cells to ensure successful engraftment. Ferritin, a key iron storage protein, is routinely evaluated during pre-collection visits, as low levels often indicate iron deficiency, which may impact stem cell capture. In some practices stem cell collection may be delayed to correct ferritin deficiencies. However, the level at which such intervention is necessary is not well known. Furthermore, delaying stem cell collection can have many implications including risk of infection, psychological stress, increased cost, and logistical challenges. The present study seeks to describe the impact of relative ferritin status on stem cell collection prior to bone marrow transplantation. Methods In a retrospective chart review of 183 patients at our center, 155 patients undergoing autologous transplantation from 2016-2018 and 2022-2023 as well as 28 allogeneic transplant donors between 2016-2023 were included. Patients and donors (n=13) who were missing ferritin levels at pre-collection or stem cell capture data in the electronic medical record (EMR) were excluded from analysis. Patient demographics, ferritin level (FL) at the pre-collection evaluation visit, total stem cell capture (TC), stem cell capture on the first day of apheresis (FC), and the total number of days of apheresis (DOA) were retrieved from the EMR. We classified patients into three groups: FL-1 had a ferritin level less than 50 ng/ml, FL-2 had a level between 50.1-500 ng/ml, and FL-3 had a level greater than 500 ng/ml. The Allogeneic donor cohort had an insufficient number of patients with high ferritin for analysis. A general linear model was used to assess the relationship between TC, DOA, and FC compared to ferritin status while covarying for age, sex, and race. Results In the allogeneic donor population, DOA (p=0.666), TC (p=0.938), and FC (p=0.961) were not statistically significant between groups FL-1 and FL-2. Additionally, there were no statistically significant differences in DOA, TC, or FC when our low ferritin cut off includes levels up to 100 ng/ml. In the autologous transplant population, there were no statistically significant differences between groups FL-1 and FL-2 regarding DOA (p=0.254) or TC (p=0.139), albeit FL-2 had a marginally higher FC (p=0.024). FL-2 had marginally lower FC (p=0.003) and TC (p=0.003) than FL-3, but DOA was not significantly different (p=0.783). Those observations held true when our low ferritin cut off includes levels up to 100 ng/ml. Conclusion Our results suggest that ferritin levels below 50 or 100 ng/ml may not warrant delaying stem cell collection in related allogeneic donors. For autologous transplants, the groups with normal ferritin levels showed slightly better first-day capture; however, the difference was not substantial enough to justify delaying collection because of its lack of effect on days of apheresis and total capture. On the other hand, high ferritin slightly increased the total and first day capture, so high levels should not delay collection either. This retrospective analysis adds valuable data to the relatively under-researched area of ferritin status in stem cell mobilization and offers insight to physicians considering collection delays.

Serum Ferritin Reflects Bone Marrow Iron Stores in Children with End Stage Kidney Disease

Background: Iron deficiency is common in children with end-stage kidney disease (ESKD) but diagnosing iron deficiency in ESKD is challenging as serum indicators of iron stores may be influenced by inflammation and other factors. We examined which of the clinically used serum iron indices were predictive of bone marrow iron stores (the gold standard) in dialysis-dependent children and young adults with ESKD, in the setting of increased nutritional requirements and co-existing inflammation. Methods: This cross-sectional study enrolled 71 clinically-stable children and young adults (age range 2 to 28 years) receiving dialysis, who underwent bone biopsy for CKD-mineral bone disorders between 2007 through 2011. Congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary diseases (63.3%) were the main causes of renal failure, followed by primary glomerulonephritis (36.7%). Bone samples were stained with Perls' Prussian blue and independently interpreted by a pathologist unaware of the patients' iron parameters and clinical status. Staining was scored absent vs present for receiver operator curve (ROC) analysis. In ROC analysis, the ability of serum ferritin to predict bone sample iron stores was compared with serum hepcidin, transferrin saturation (TSAT), and clinical guideline-based iron deficiency cut-offs for serum iron, TSAT, and their combination. We generated optimal cut off points using the Youden's J statistic. Results: Mean age was 17.2 ± 4.4 years, and 30% of subjects were female. Median dialysis vintage was 1.2 (IQR 0.7, 2.0) years, and 56% were supported by peritoneal dialysis. Mean hemoglobin was 12.4 ± 1.7 g/dl, and 35% were receiving iron supplementation at the time of biopsy. Based on gold standard of depleted bone iron stores, 46.5% patients were iron-deficient. As a predictor of bone marrow iron staining, serum ferritin provided the highest area under the ROC curve compared to other tests (Table), but at the usual clinical ferritin cutoff (100 ng/ml) only 22% of true iron-deficient subjects were diagnosed compared to 52% of true iron-deficient subjects using a higher optimal cutoff point for ferritin (188 ng/ml). Conclusions: In children with ESKD, iron deficiency as determined by the gold standard bone iron staining was highly prevalent (close to 50%), and serum ferritin provided the best prediction of bone sample iron stores. Optimal ferritin cutoff for decision-making about iron administration should reflect the current relative risks and benefits of iron therapy. Future trials testing higher ferritin cut-offs and patient centered outcomes in children with ESKD are timely.

Simulated effects of ferritin screening on C-reactive protein levels in recruited blood donors.

Ferritin is commonly measured to evaluate iron stores in the body. Some countries have added or considered adding ferritin lower bounds to donor eligibility criteria. Ferritin is also elevated by inflammation. The main goal of this study is to estimate how different ferritin cut-offs would affect the proportion of donors with a C-reactive protein (CRP) level over 3 mg/L, which is the decision limit of the highest chronic cardiovascular risk. To simulate recruitment of new blood donors, we selected participants from two Finnish general population cohorts, namely FINRISK 1997 (n = 5369) and Health 2000 (n = 3278), that would likely fulfil the selection criteria of blood donation. We then calculated the proportion of individuals with high-sensitivity CRP values above 3 mg/L, over a range of ferritin values. We found that for several ferritin cut-offs the proportion of potential donors with CRP > 3 mg/L would rise by a statistically significant amount. The trend was significant and similar for all subgroups but weaker for non-menstruating women as well as men. Our results show that screening a population of potential blood donors with ferritin cut-offs raises the number of people with CRP > 3 mg/L within the blood donor population.

The usefulness of ferritin as a biomarker in evaluating the severity of disease in wave one and wave two of COVID-19 patients – A comparative retrospective study

Background: Serum ferritin was found to be a positive acute phase protein and it was linked to a hyperinflammatory process, cytokine storm, and multiple organ damage in coronavirus disease (COVID-19). Objective: The objective of this study was to establish whether ferritin could be utilized as a biomarker to evaluate disease severity in COVID-19 waves one and two in hospitalized patients. Materials and Methods: It was an observational, retrospective study. A total of 2093 patients’ data with confirmed reverse transcriptase-polymerase chain reaction positive for COVID-19 disease were reviewed. Serum ferritin values on the day of hospital admission were compared in both waves among different grades of clinical severity correlated in terms of survival and death. Results: Survivors in wave one were 92.5% and 85.4% in wave two. In waves one and two, the nonsurvivor rate was 7.5% and 14.6%, respectively, with statistically significant P values of 0.001. Analysis of the receiver operating curve (ROC) showed the ideal ferritin cutoff point for death is 687.6 ng/mL (sensitivity: 70%; specificity: 57.3%), with an Area under curve (AUC) of 0.67, suggesting that ferritin was a better marker of mortality and severity in the first wave. In the second wave, the cutoff for severity is 583.9 ng/mL (sensitivity of 85.1%, specificity of 54.8%). AUC 0.74 suggested a marker of severity in the second wave. Conclusion: Elevated serum ferritin levels in the first wave indicated severity and mortality with exaggerated cytokine storm and early organ damage and severity in the second wave, indicating reduced inflammation and better treatment plan.

Utility of Ferritin at Registration as a Screen for Development of Anemia in Third Trimester [ID: 1362276

INTRODUCTION: The objective of this study was to assess the utility of screening ferritin (&lt;20 weeks of gestation) in pregnant patients on hemoglobin (Hgb) and hematocrit (Hct) later in gestation. METHODS: Pregnant patients who received nondiagnostic ferritin labs at less than 20 weeks of gestation from 2019 to 2021 were retrospectively identified. Patients were excluded if ferritin testing was conducted for diagnostic purposes or if the patient had a history of anemia. Labs at the time of registration, 28 weeks of gestation, and at delivery were analyzed. Anemia was defined as Hgb less than 11 g/dL. This study was approved by the University of Washington IRB, and patient consent was waived. RESULTS: Forty-four patients underwent routine ferritin screening at registration, with ferritin levels ranging from 10 to 136 ng/mL (average 52.5 ng/mL). Average Hgb/Hct at registration were 12.6 g/dL and 37.3%, respectively. At 28 weeks of gestation, Hgb/Hct were obtained on 42 patients, of whom 9 patients were diagnosed with anemia. Patients diagnosed with anemia had a screening ferritin level of 33.6 ng/mL, and nonanemic patients had a ferritin level of 57.4 ng/mL (P=.1). When a cutoff of 50 ng/mL was studied to compare patients with “low” versus “normal” ferritin, ferritin less than or equal to 50 ng/mL had significantly lower Hgb levels at 28 weeks compared to those with ferritin greater than 50 ng/mL (P=.013). On labor and delivery (L&amp;D), Hgb/Hct was obtained on 44 patients, and 14 were diagnosed with anemia. Anemic patients on L&amp;D had significantly lower screening ferritin compared to nonanemic, 31.9 and 62.2 ng/mL, respectively (P=.016). CONCLUSION: Ferritin screening in early pregnancy may help predict lower Hgb in later gestation. Using a higher ferritin cutoff of 50 ng/mL in early pregnancy for identifying patients at risk for anemia in the third trimester may be warranted. Larger prospective studies are needed to evaluate further the utility of ferritin screening.

Ferritin and its association with anaemia in a healthy adult population in Kenya.

BackgroundIron deficiency is the commonest cause of anaemia worldwide. Serum ferritin is the most sensitive non-invasive indicator of iron stores but its utility is compromised in inflammatory states as it is an acute phase reactant. This study sought to estimate the burden of iron deficiency in a healthy adult population residing in Kenya and to determine the association between various ferritin cut-offs and anaemia in a population known to have chronic low-grade inflammation.MethodsHealthy adults aged 18–65 years were recruited from urban towns in 4 counties in Kenya at average altitudes of 1683-2099m above sea level as part of a global study conducted by the International Federation of Clinical Chemistry (IFCC) to determine reference intervals (RIs) for common laboratory tests. We analyzed complete blood count (CBC), C-reactive protein, iron, transferrin, transferrin saturation and ferritin data.ResultsWe obtained data from 528 participants. There were 254 (48.1%) males and 274 females (51.9%). Based on a ferritin cut-off of 15 μg/L and Hb cut-offs of 14.5 g/dL and 12 g/dL, the prevalence of iron deficiency anaemia was 0.8% and 7.3% in males and females respectively. The odds of having anaemia was highest if one had a ferritin value less than 15 μg/L with a sensitivity of 28.6% and specificity of 98.4% in males, and sensitivity of 83.3% and specificity of 78.0% in females.ConclusionOnly the ferritin cut-off of 15 ug/L had an association with anaemia where it can be used for ruling out iron deficiency as the cause. Sex specific ferritin cut-offs for diagnosing iron deficiency in adults in sub-Saharan Africa need to be derived by comparing ferritin levels to stainable iron in bone marrow aspirates and trephines in order to ensure that we are using appropriate clinical decision limits.

Diagnostic utility of clinical characteristics, laboratory tests, and serum ferritin in diagnosis of adult-onset Still disease.

The diagnosis of adult-onset Still disease (AOSD) is challenging with ambiguous clinical presentation and no specific serological markers. We aim to evaluate the diagnostic utility of clinical, laboratory and serum ferritin features in established AOSD patients. We included all patients >18 years who were admitted to 2 tertiary medical centers (2003–2019) with serum ferritin above 1000 ng/mL. AOSD patients and non-AOSD controls were matched in 1:4 ratio for age and sex. The primary outcomes were sensitivity, specificity, positive/negative likelihood ratio and area under the curve (AUC) using clinical and laboratory characteristics based on the Yamaguchi classification criteria, in addition to serum ferritin. We identified 2658 patients with serum ferritin above 1000 ng/m, of whom 36 diagnosed with AOSD and 144 non-AOSD matched controls. Presence of arthralgia/arthritis showed the highest sensitivity (0.74), specificity (0.93), positive likelihood ratio (10.69), negative likelihood ratio (0.27) and AUC (0.83, 95% confidence interval 0.74–0.92) to the diagnosis of AOSD. On the other hand, serum ferritin showed variation and poorer results, depends on the chosen ferritin cutoff. Joint involvement showed the best diagnostic utility to establish the diagnosis of AOSD. Although clinicians use often elevated ferritin levels as an anchor to AOSD, the final diagnosis should be based on thorough clinical evaluation.

Iron homeostasis in heart transplant recipients randomized to ferric derisomaltose or placebo.

IntroductionThe randomized IronIC trial evaluated the effect of intravenous ferric derisomaltose on physical capacity in iron‐deficient, maintenance heart transplant (HTx) recipients. Iron deficiency was defined as in heart failure with high cut‐points for ferritin to compensate for inflammation. However, intravenous iron did not improve physical capacity except in patients with ferritin <30 μg/L. We aimed to explore determinants of iron status in the 102 IronIC participants to better define iron deficiency in the HTx population.MethodsWe assessed key governors of iron homeostasis, such as hepcidin, soluble transferrin receptor (sTfR), and interleukin‐6 (IL‐6). We also measured growth factors and inflammatory markers with relevance for iron metabolism. The results were compared to those of 21 healthy controls.ResultsHepcidin did not differ between HTx recipients and controls, even though markers of inflammation were modestly elevated. However, HTx recipients with ferritin <30 μg/L or sTfR above the reference range had significantly reduced hepcidin levels suggestive of true iron deficiency. In these patients, intravenous iron improved peak oxygen uptake. Hepcidin correlated positively with ferritin and negatively with sTfR.ConclusionHTx recipients with iron deficiency as defined in heart failure do not have elevated hepcidin levels, although inflammatory markers are modestly increased. The high ferritin cut‐offs used in heart failure may not be suitable to define iron deficiency in the HTx population. We suggest that hepcidin and sTfR should be measured to identify patients with true iron deficiency, who might benefit from treatment with intravenous iron.

Serum Ferritin Levels for the Prediction of Mortality among COVID-19 Patients in an Indonesia’s National Referral Hospital

BACKGROUND: Early identification of clinical outcomes is necessary for risk classification in COVID-19 patients. This study help in evaluating the progression of the disease and the patient’s therapy. AIM: This study aims to determine serum ferritin levels for the prediction of mortality among COVID-19 patients in an Indonesia’s National Referral Hospital. METHODS: A retrospective cohort study was conducted on 142 confirmed positive COVID-19 patients between March 2020 until March 2021 at Dr. M. Djamil General Hospital as a National Referral Hospital in Indonesia. Data obtained from medical record documents and examination of ferritin levels was carried out at the beginning of treatment. The Chi-square test and survival analysis with the log-rank test and Kaplan–Meier methods were used to analyze the data. The SPSS version 15 was used to analyze the data. RESULTS: The serum ferritin cutoff point for COVID-19 patients that can be used to predict poor outcomes was &gt;651.02 ng/mL with sensitivity 79.3%, specificity 80.5%, and accuracy 85.0%. Age, comorbid diabetes mellitus, number of comorbidities, symptoms of trouble breathing, oxygen saturation, severity, and mortality outcome were all associated to ferritin levels &gt;651.02 ng/mL. The Kaplan–Meier curve showed that ferritin levels &gt;651.02 ng/mL were associated for risk of poor outcome COVID-19 patients (HR = 8.84, [95% CI 3.59–21.73]). CONCLUSION: The ferritin cutoff point for predicting poor prognosis in COVID-19 patients was 651.02 ng/mL. However, ferritin serum levels cannot be used as a single predictor in determining the poor outcome of COVID-19.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

Adjusting Ferritin Concentrations for Nonclinical Inflammation in Adolescents with Overweight or Obesity

To compare approaches for adjusting serum ferritinconcentrations for inflammation in Chilean adolescents with overweight and obesity. Cross-sectional data from 518 adolescents (aged 16-17years; 48% females) from Santiago, Chile were analyzed. Several approaches were compared for estimating the prevalence of depleted iron stores (defined as serum ferritin <15μg/L), including unadjusted prevalence and higher cutoffs for various subgroups (excluding participants with inflammation), correction factors, and regression corrections. A "reference" prevalence estimate was calculated as the prevalence of serum ferritin <15μg/L in normal weightindividuals without inflammation. Each adjustment approach was compared with this reference prevalence. The sample comprised 61.2% normal weight, 23.7% overweight, and 15.1% obese individuals. The prevalence of inflammation (marked by C-reactive protein level >5.0mg/L) was 6.3%, 8.1%, and 14.1% in the 3 groups, respectively. The correction factor approaches produced adjusted estimates closest to the reference estimate (24.1%-24.7% vs 22.9%), followed by the regression corrections (24.7%-25.1% vs 22.9%). Applying a higher serum ferritin cutoff (30μg/L) to all participants or to participants with overweight/obesity produced adjusted estimates farthest from the reference (59.5% and 35.3%, respectively). Adjusting serum ferritin concentration may be necessary when assessing iron status in populations with high rates of overweight/obesity. After reviewing 6 approaches for adjusting for the influence of inflammation, this study suggests that using correction factors may be the most appropriate approach for adjusting serum ferritin in Chilean adolescents. Further research is needed to determine the optimal approach for adjusting serum ferritin concentrations for weight-related inflammation in broader populations.

Cutoff Values for Serum Ferritin in Predicting Cirrhosis Severity due to Cholestatic Jaundice in Vietnamese Children.

Background:High serum ferritin levels are associated with liver cirrhosis severity and worse outcomes for hepatopathies. This study determined the serum ferritin cutoff values for predicting cirrhosis severity in children with cholestatic jaundice.Methods:A retrospective study was performed, including all cases diagnosed with cirrhosis in children aged 1 month to 16 years at Children’s Hospital 2-Vietnam between 2016 and 2021. Receiver operating characteristic (ROC) curve analysis was used to estimate ferritin cutoff values for predicting disease severity.Results:The study included 95 patients with cirrhosis due to cholestatic jaundice. Decompensated cirrhosis accounted for the majority (74.7%) of cases. Increased serum ferritin concentrations predicted cirrhosis severity in children, and the optimal ferritin cutoff value for predicting decompensated cirrhosis was determined to be 195 μg/l, resulting in a sensitivity of 65.22%, a specificity of 95.83%, and an area under the ROC curve (AUC) or 0.82. The Child–Pugh C group had higher ferritin levels than the Child–Pugh A and B group (p < 0.001), and the ferritin cutoff value for distinguishing between Child–Pugh classifications was 195 μg/l, resulting in a sensitivity of 71.2%, a specificity of 87.9%, and an AUC of 0.80.Conclusions:Serum ferritin levels are significantly associated with decompensated cirrhosis and disease severity (as assessed by Child–Pugh score). Routine serum ferritin testing may contribute to predicting cirrhosis severity in children.

Iron Deficiency: A New Target for Patients With Heart Failure.

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.

Iron Status of Icelandic Blood Donors and the Impact of Different Ferritin Assay Platforms on Donor Deferral Rates

Introduction: In a single blood donation a donor loses approximately 250 mg of iron. Serum ferritin is an accepted and widely used method for determining iron status and is used to assess the iron status of all new and selected active blood donors in the Blood Bank in Iceland. The World Health Organization defines depleted iron stores as ferritin <15 μg/l, but at our institution the ferritin cut-off for active blood donors has been >8 μg/l. Where ferritin assays are used to determine donor eligibility status, the accuracy of these assays is critical. We have noticed discrepancies between the results of paired ferritin measurements on different ferritin immunoassay platforms, both between local laboratories and on external control reports.Objective: The objectives of this study were 1) to examine the iron status of Icelandic blood donors and assess the frequency of iron deficiency in new and active donors, in both genders and different age groups, 2) to compare serum ferritin measurements between two laboratories using different platforms, and 3) to assess the potential impact of using different platforms on donor deferral rates.Methods: A retrospective study of blood donor ferritin results was performed in the Blood Bank for the calendar years 2015 and 2016. Blood donor data were obtained through the laboratory information system (ProSang®). For comparison of ferritin measurements between different platforms 106 blood samples from blood donors were obtained and ferritin measured both at the Blood Bank (Vitros®) and the hematology laboratory at Landspítali (Cobas®). Both platforms are based on the same technique which is a two-step sandwich ELISA. Data was analyzed using Excel and the R program.Results: The median ferritin value for new blood donors was 51 μg/l (n = 3529); more specifically 86.4 μg/l for men (n = 1824) and 26.6 μg/l for women (n = 1705). The frequency of iron deficiency (ferritin <15μg/l) among new blood donors was 11%; 1% in men and 22% in women. Ferritin results were available for approximately 15% of active blood donors. The median ferritin value for active donors was 27.8 μg/l (n = 3223); more specifically 32.9 μg/l for men (n = 2159) and 20.8 μg/l for women (n = 1064). Among new donors ferritin levels were on average lowest in the youngest age groups for both genders, but increased with higher age, gradually among men and after age 40 among women (figure 1A). Donor age had less impact on ferritin levels in active blood donors. A proportional bias was observed between ferritin measurements for the two different instruments/laboratories (figure 1B). Good correlation was only observed between measurements at the lowest values (<5 μg/l) but correlation decreased with higher ferritin values. As an example a single donor sample gave ferritin values of 9.91 μg/l using Vitros but 15 μg/l using the Cobas. Of the 106 donors providing samples for paired measurements, 9% would be deferred as blood donors due to low ferritin (<15 μg/l) using the Vitros assay whereas only 2% would be deferred using the Cobas analyser. As the Vitros consistently gave lower ferritin values, using this instrument in the Blood Bank will lead to increased donor deferral rates due to low ferritin compared to the Cobas.Conclusion: One fourth of newly registered female blood donors were iron deficient. It is important to monitor ferritin in blood donors to prevent the development of iron deficiency. A prospective study of iron stores in active donors is needed to establish the prevalence of iron deficiency in this population. The proportional bias observed between the two instruments/laboratories for ferritin assays underlines the importance of taking instrument-related performance into account when establishing ferritin cut-offs for blood donor deferral. Using a more “sensitive” assay will lead to fewer donor deferrals due to iron deficiency but may cause increased deferrals due to high ferritin levels. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Optimizing the Management of Iron Overload in Patients with Hemoglobin Disorders in Centers with Limited Access to Magnetic Resonance Imaging

Background:Transfusion therapy for severe chronic anemias is a major cause of iron overload. Patients with hemoglobin disorders are often transfused, either chronically or occasionally, and if iron overload is suspected, it is currently recommended they are subjected to so-called “iron studies” and determination of liver iron content (LIC) and heart T2* by magnetic resonance imaging (MRI). It remains common practice to request both laboratory and imaging tests, even for patients already undergoing iron chelation, despite the unreliability of laboratory markers such as ferritin in the presence of concurrent inflammatory conditions, which do not affect results from MRI scans. Since MRI is not widely available in most underdeveloped and developing countries, we aimed to assess the contribution of laboratory tests to the management of patients with hemoglobin disorders with iron overload by analyzing a cohort of patients who managed to undergo MRI during a period of limited access to MRI scans in our center.Methods: In this single-center, retrospective analysis, data were collected from digital MRI, laboratory information system, and electronic chart databases, upon approval of the local ethics board. Since access to MRI was limited during the period of time studied, physicians used the following criteria to indicate MRI scans to define clinical suspicion of iron overload: patient already undergoing chelation therapy based on previous laboratory tests and clinical assessment, current or previous chronic transfusion therapy, or elevated ferritin with transferrin saturation (TSAT) above 45%.Results and Discussion: From April 2014 to September 2016, 27 patients (17 with sickle cell disease - SCD, 10 with beta thalassemia - BT), median age 35 years (15-62), 9 male (33%), were evaluated at 34 different occasions with MRI and conventional iron studies. Patients with BT had significantly higher levels of serum iron and TSAT than patients with SCD (BT median 266ug/dL, range 93-328 and 0.94, range 0.41-1.00; SCD median 157ug/dL, range 58-264, and 0.64, range 0.21-1.00, P=0.004 and P=0.0138), which reflects a higher percentage of BT patients on chronic transfusions (8/11 vs. 6/17) and the higher transfusion volume for BT in comparison to what is needed for exchange transfusions in SCD. Four patients had normal MRI scans: 1 with SCD not in transfusion, 1 with SCD that had been treated with iron chelation, and 2 BT major in chronic transfusion and optimal response to iron chelation (ferritin <500ng/mL). Only one SCD and one BT patient were diagnosed with cardiac iron overload, with a T2* of 7.5ms and 2.95ms, respectively, in patients with extreme hyperferritinemia (11,567 and 7,090ng/mL) and low compliance to iron chelation. MRI liver iron concentration correlated positively with serum ferritin and total iron binding capacity (TIBC) measurements (r=0.67, 95% CI 0.41-0.83, P <0.0001, and r=-0.49, 95% CI -0.72 to -0.17, P <0.004, respectively) but no serum biomarkers correlated with myocardial iron concentrations. Receiver operating characteristic (ROC) curve analysis showed that ferritin levels performed best in our population as predictor of any increase of LIC above 2mg/g (area under curve 0.9753, P=0.0003), with a cutoff value of 731.6ng/mL with a sensitivity of 96.3% and specificity of 100% to discriminate for the presence of any increase in hepatic iron. In addition, a ferritin cutoff value of 1649ng/mL yielded 76.2% sensitivity and 91.7% specificity to detect a LIC above 5mg/g, comprising 17 (50%) of the MRI scans. Only one patient in this group had less than moderate liver iron overload, but still with an abnormal LIC of 3.5mg/g.Conclusions: Our data suggest that conventional iron studies cannot predict cardiac siderosis, but earlier evaluation with MRI may be warranted in the presence of clinical risk factors such as history of chronic transfusion along with low compliance to iron chelation, independently from laboratory tests. In settings with limited access to MRI, ferritin levels may be useful in pre-screening for hepatic iron overload, so postponing probable negative scans for patients undergoing iron chelation with optimal response or probable positive scans for those with certain levels of hyperferritinemia (e.g.>1649mg/dL) could be appropriate criteria to manage referrals to MRI scans and help prioritize patients with undetermined indication of iron chelation. DisclosuresFertrin:Alexion Pharmaceuticals: Consultancy.