Ferritin Cutoffs and Diagnosis of Iron Deficiency in Primary Care.

Importance: 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. Objective: To investigate the association of the ferritin cutoff choice with the incidence of nonanemic and anemic iron deficiency diagnoses in primary care. Design, Setting, and Participants: 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. Exposures: Sex, age, clinical patient characteristics, and professional general practitioner characteristics. Main Outcomes and Measures: 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). Results: 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. Conclusions and Relevance: 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.

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.

Mistakes in the management of iron deficiency anaemia: a narrative review.

INTRODUCTION: Anaemia occurs due to an imbalance between erythrocyte production and loss. This imbalance can be due to ineffective erythropoiesis, blood loss or haemolysis. Whilst there are many causes for anaemia, iron deficiency anaemia (IDA) remains the predominant cause worldwide. AREAS COVERED: There have been many updated guidelines on the management of IDA in the past few years. As the reasons for IDA are many, evaluation requires thorough analysis and focused investigations. As an asymptomatic disease in the early stages, IDA can lead to many mistakes in its management. This review highlights potential mistakes in assessing and managing IDA and recommendations to avoid them. CONCLUSION: The effective management of IDA necessitates a comprehensive and multidisciplinary approach. By recognising and addressing the common mistakes highlighted in this narrative review, healthcare professionals can improve patient outcomes, minimise complications, and enhance the overall quality of care.

Current approach to the management of preoperative iron deficiency anemia in colorectal cancer patients: a review of literature.

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

[Diagnosis and treatment of iron deficiency anemia].

The causes of iron deficiency anemia include blood loss, increased demand, insufficient dietary intake, and disorders affecting iron absorption. In certain circumstances, atrophic gastritis, either autoimmune or due to Helicobacter pylori infection, may contribute. On very rare occasions, iron-refractory iron deficiency anemia can develop as a consequence of TMPRSS6 mutations. Iron deficiency anemia is diagnosed by identification of microcytic hypochromic anemia with low serum ferritin levels. In cases of chronic disorders such as chronic kidney disease, chronic heart failure, and chronic inflammatory disorders, the diagnosis may also incorporate transferrin saturation. Treatment of underlying diseases is recommended along with iron supplementation. While oral iron supplements are the first choice, intravenous iron may be considered when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. Recently, high-dose intravenous iron formulations became available in Japan, but their use requires caution due to potential risks of allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage. Notably, the benefits of high-dose intravenous iron for patients with heart failure and iron deficiency are recognized in the field of cardiology. This article provides an overview, incorporating recent developments in the field of iron deficiency anemia.

INVESTIGATION OF IRON DEFICIENCY IN POSTMENOPAUSAL WOMEN BASED ON LABORATORY TESTING: A UNI-CENTRE STUDY.

Objectives - postmenopausal women (PMW) undergo a physiological phase of lack or insufficient female sex hormones resulting in some consequences including hematological deficits. The present study aimed to investigate the detection of anemia in postmenopausal women using easy laboratory tools. In this retrospective analysis of patient data collected during the period between 2014-2022. Data retrieved from PMW records were collected over 4 years and analyzed. In comparison to normal ranges, data of PMW has shown reduced levels of hemoglobin, packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin. PMW has also shown elevated levels of red cell distribution width and levels of serum iron. Compared to normal ranges, no changes have been seen regarding red blood cell count, Mean corpuscular hemoglobin concentration, unsaturated or total iron binding capacity, transferrin saturation, serum ferritin, white blood cells count, and platelets. To provide in-depth investigation, we divide our participants into three groups according to their ages: 45-55 years, 56-65 years, and 66-80 years. The older the age, the more parameters are altered. The study highlighted the potential impact of postmenopausal hormone alteration on hematological parameters and the routine laboratory tools could be used to assess such alteration in blood parameters.

Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron-Deficiency Anemia Using Machine Learning Algorithms.

OBJECTIVE: In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group. METHODS: This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non-diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K-Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model. RESULTS: According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients. DISCUSSION: Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision-making processes.

The origin of ferritin reference intervals: a systematic review.

Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than 30 µg/L has a high specificity and sensitivity for diagnosing iron deficiency in adults, but the laboratory reported lower limit of normal (LLN) is typically lower. These LLNs might not be rooted in rigorous scientific evidence and might be contributing to structural underdiagnosis of iron deficiency. A systematic review was done per systematic reviews and meta-analysis guidelines with the use of medical literature databases from inception of each database to Nov 30, 2021, to identify studies that determined ferritin reference intervals in healthy adults and grey literature search for the five most common ferritin assays (registration number CRD42022268844). The objectives were to systematically summarise the ferritin reference intervals and to do a methodological quality assessment of the included studies. 2306 studies were screened and 61 full texts were included. 37 studies were eligible for analysis of the ferritin LLN in the general population. The population the sample was comprised of was a total of 21 882 females and 23 650 males participants. The ferritin LLN was a median of 8 µg/L (IQR 5-15) and mean of 9 µg/L (SD 11) in females and a median of 25 µg/L (IQR 16-44) and mean of 25 µg/L (SD 29) in males. 30 (49%) of 61 studies did not explicitly screen for patients at risk of iron deficiency, and 32 (52%) did not refer to a reference interval establishment guideline (eg, guideline recommended by Clinical and Laboratory Standards Institute). The five most used commercial ferritin laboratory assays reported reference intervals with a median LLN of 11 (IQR 9-12) and mean of 9 µg/L (SD 4) for females and median of 22 (IQR 22-24) and mean of 23 µg/L (SD 4) for males. In the literature, serum ferritin reference intervals in healthy adults consistently report a LLN of less than 30 µg/L. Data driving these ferritin reference intervals are at high risk of bias, given no exclusion of individuals at risk for iron deficiency in the presumed normal population sample and no adherence to reference interval establishment standards. We suggest the use of evidence-based laboratory clinical decision limits to diagnose iron deficiency.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Prevalence of Iron Deficiency Using 3 Definitions Among Women in the US and Canada.

Importance: The prevalence of iron deficiency varies widely according to how it is defined. Objective: To compare the prevalence of iron deficiency among women using 3 different definitions. Design, Setting, and Participants: The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care-based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023. Main Outcomes and Measures: Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]). Results: Among 62 685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40 381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62 685 women increased 2.4-fold (95% CI, 2.3-2.5; P < .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P < .001) using the IDE definition. Conclusions and Relevance: Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.

[Guidelines for uniform management of breath-holding spells]. / Nya handläggningsrutiner för affektanfall hos barn föreslås.

Witnessing breath-holding spells (BHS) can be distressing and patients with BHS disproportionately consume a substantial amount of health care resources. Common among preschool children, BHS follow a distinct sequence of events. A comprehensive patient history is the primary diagnostic tool. BHS lacked standardized diagnostic criteria and guidelines until our recent Acta Paediatrica publication. Studying 519 BHS cases in Skåne (years 2004-2018), we found overuse of electrocardiograms (ECGs) and electroencephalograms (EEGs), and underuse of blood tests for treatable iron deficiency and anemia, both known BHS contributors. Building upon our cohort analysis, we refined the definition of BHS and introduced a clinical management algorithm. Simulations showed reduced EEG and ECG use and an increase in blood tests. Our guideline not only streamlines diagnostic processes, but also optimizes the allocation of healthcare resources for more effective and targeted interventions.

Assessment of iron status.

PURPOSE OF REVIEW: Iron is an essential trace element in human health that can be harmful at abnormal levels such as iron overload or deficiency. Measured iron status in the body can depend on health outcomes experienced by the individual and this can complicate its accurate assessment. This review will highlight recent research on iron assessment in the literature. RECENT FINDINGS: Research on iron assessment within the past 18 months included some common themes spanning new methods and biomarkers, as well as existing problems in assessing iron deficiency and overload. Heterogeneity in associations between inflammation and iron levels are reflected across different inflammatory biomarkers. New methods relevant to low- and high-resource settings may improve assessment in tissues with iron deficiency and overload. Consensus papers outlined best practices when using MRI to assess iron status. Outside of newer methods, traditional serum markers are the subject of a call for updated guidance when assessing iron status. SUMMARY: Research continues on the topic of iron assessment, underlying its complex metabolism in the body and resulting challenges in assessment. Current literature underscores progress to make iron assessment more accessible, improve existing methods, and update current assessment methods so they correspond with recent research to improve human health.

Prevalence of iron deficiency and anemia in pediatric heart transplant recipients.

INTRODUCTION: The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin < 30 ng/mL ± transferrin saturation < 20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. METHODS: Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients (<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. RESULTS: Median age at transplant was 3 years (IQR .5-12.2). The median ferritin level was 32 ng/mL with 46% having ferritin < 30 ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT < 20%. Median hemoglobin was 11 g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT < 20%, and estimated glomerular filtration rate <75 mL/min/1.73 m2 were independently associated with anemia. Ferritin < 30 ng/mL in isolation was not associated with anemia. Ferritin < 30 ng/mL may aid in detecting absolute iron deficiency while TSAT < 20% may be useful in identifying patients with functional iron deficiency ± anemia in pediatric HTx recipients. CONCLUSION: Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.

A novel discriminant algorithm for differential diagnosis of mild to moderate thalassemia and iron deficiency anemia.

BACKGROUND: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA. METHODS: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices. RESULTS: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987). CONCLUSION: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China.

Redefining Iron Deficiency in Patients With Chronic Heart Failure.

A serum ferritin level <15 to 20 µg/L historically identified patients who had absent bone marrow iron stores, but serum ferritin levels are distorted by the systemic inflammatory states seen in patients with chronic kidney disease or heart failure. As a result, nearly 25 years ago, the diagnostic ferritin threshold was increased 5- to 20-fold in patients with chronic kidney disease (ie, iron deficiency was identified if the serum ferritin level was <100 µg/L, regardless of transferrin saturation [TSAT], or 100 to 299 µg/L if TSAT was <20%). This guidance was motivated not by the findings of studies of total body or tissue iron depletion, but by a desire to encourage the use of iron supplements to potentiate the response to erythropoiesis-stimulating agents in patients with renal anemia. However, in patients with heart failure, this definition does not reliably identify patients with an absolute or functional iron-deficiency state, and it includes individuals with TSATs (≥20%) and serum ferritin levels in the normal range (20-100 mg/L) who are not iron deficient, have an excellent prognosis, and do not respond favorably to iron therapy. Furthermore, serum ferritin levels may be distorted by the use of both neprilysin and sodium-glucose cotransporter 2 inhibitors, both of which may act to mobilize endogenous iron stores. The most evidence-based and trial-tested definition of iron deficiency is the presence of hypoferremia, as reflected by as a TSAT <20%. These hypoferremic patients are generally iron deficient on bone marrow examination, and after intravenous iron therapy, they exhibit an improvement in exercise tolerance and functional capacity (when meaningfully impaired) and show the most marked reduction (ie, 20%-30%) in the risk of cardiovascular death or total heart failure hospitalizations. Therefore, we propose that the current ferritin-driven definition of iron deficiency in heart failure should be abandoned and that a definition based on hypoferremia (TSAT <20%) should be adopted.

Double balloon enteroscopy versus single balloon enteroscopy: A comparative study.

Device assisted enteroscopy (DAE) like the double balloon enteroscopy (DBE) and single balloon enteroscopy (SBE) are postulated to ease small bowel examination and performance of therapy. However, studies comparing the effectiveness of these 2 modalities have yielded varying results. The aim of this study is to compare the efficacy and safety of SBE and DBE. We retrospectively reviewed records of patients who underwent DBE (n = 82) or SBE (n = 45) for small bowel exam in our unit from January 2014 to January 2022. Our primary outcomes were to compare the technical success and diagnostic success rates between DBE and SBE. Our secondary outcomes were to compare the therapeutic success, and complication rates. The main indications were suspected GI bleeding (DBE 41.5% vs SBE 48.9%), iron deficiency anemia (DBE 9.8% vs SBE 4.4%) and small bowel lesions (DBE 28.0% vs SBE 44.4%) detected either from prior capsule endoscopy or radiological imaging. Majority of the enteroscopy exam was by antegrade approach (DBE 67.1% vs SBE 77.8%). We found no significant difference in the technical success (DBE 95.1% vs SBE 97.8%, P = .46), diagnostic success (DBE 69.5% vs SBE 77.8%, P = .36) and the therapeutic success rate (DBE 63.2% vs SBE 54.3%, P = .09) between the groups. Complications occurred in 1 case from each group (mucosal tear). None of the complications were major. In patients who underwent enteroscopy, the diagnostic and therapeutic performance of SBE is similar to DBE. Both procedures were safe with low complication rates.

Serum ferritin and risk of colonic neoplasia: Implications for the workup and treatment of iron deficiency.

Iron deficiency is the most common extraintestinal sign of colonic neoplasia, including colorectal cancer (CRC) and other lower gastrointestinal pathology. Both upper endoscopy and colonoscopy is usually recommended in the work-up of patients with unexplained iron deficiency, particularly in men and postmenopausal women. As the incidence of early-onset CRC (age <50 years) rises in the United States, there is an increasing need to identify risk predictors to aid in the early detection of CRC. It remains unknown if serum ferritin (SF), and what specific threshold, can be used as a marker to stratify those at risk for CRC and other lower gastrointestinal pathology. In this current review of the literature, we aimed to review guidelines for diagnostic workup of colonic neoplasia in the setting of iron deficiency and examine the association and specific thresholds of SF and risk of CRC by age. Some of the published findings are conflicting, and conclusions specific to younger patients are limited. Though further investigation is warranted, the cumulative findings suggest that SF, in addition to considering the clinical context and screening guidelines, may have potential utility in the assessment of colonic neoplasia.