American Society of Hematology 2026 guidelines for diagnosis of iron deficiency.

Summary of recommendations

These guidelines are based on updated and original systematic reviews of evidence conducted under the direction of the University of Kansas Health System. The panel followed best practices for guideline development.1,2 The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty in the evidence and formulate recommendations.3

Iron deficiency is a common micronutrient deficiency and may occur with or without anemia. Individuals with iron deficiency experience symptoms including, but not limited to, fatigue, pica, irritability, poor concentration, headaches, and restless legs syndrome. Highest-risk individuals include young children and individuals who are menstruating or pregnant, with prevalence being the highest in women; persons of lower socioeconomic status are disproportionately affected.

Individuals with gastrointestinal conditions (eg, celiac disease, inflammatory bowel disease, and those who have undergone bariatric surgery), dietary restrictions, blood loss, or other chronic conditions (eg, heart failure, rheumatologic disease, chronic kidney disease) are also at risk. Management includes administration of oral or IV iron replacement therapy, as well as steps to address the underlying etiology, which may include dietary modifications and/or therapy to control or minimize blood loss. Iron deficiency is an underrecognized condition because of lack of screening in high-risk populations as well as variability in laboratory reference ranges, which often include values within the deficient range, leading to underdiagnosis and undertreatment.

Interpretation of strong and conditional recommendations

The strength of a recommendation is expressed as either strong (“the guideline panel recommends…”) or conditional (“the guideline panel suggests…”) and should be interpreted as described in Figure 1.Figure 1.Strength of recommendations.

Interpretation of good practice statements

Good practice statements endorse interventions or practices that the guideline panel agreed have unequivocal net benefit yet may not be widely recognized or used.4 Good practice statements in these guidelines are not based on a systematic review of available evidence. Nevertheless, they may be interpreted as strong recommendations.

Recommendations

Diagnosis of iron deficiency in children

Recommendation 1

For infants and children aged 9 months to 4 years, the American Society of Hematology (ASH) guideline panel suggests using a serum ferritin threshold of ≤20 ng/mL instead of a threshold of ≤12 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).

Remarks:•This threshold is for infants and children without known or suspected inflammation, and a higher serum ferritin threshold may be required for children with inflammation.•Because of a lack of direct evidence, specific recommendations for children aged >4 years until adolescence (defined as age ≥11 years5 as per the American Academy of Pediatrics [AAP]) and nonmenstruating adolescents were not developed. For children aged >4 years until adolescence, a serum ferritin threshold of ≤20 ng/mL is appropriate for the diagnosis of iron deficiency by indirectly applying evidence for young children. For nonmenstruating adolescents, a serum ferritin threshold of ≤30 ng/mL is appropriate for the diagnosis of iron deficiency by indirectly applying evidence from menstruating adolescents and adult populations.•For menstruating adolescents, please see recommendation 3.

Diagnosis of iron deficiency in adults (excluding menstruating and pregnant individuals)

Recommendation 2

For the adult population (excluding menstruating or pregnant individuals), the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL instead of ≤15 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Table 1.Signs and symptoms associated with and risk factors for iron deficiency in nonmenstruating, nonpregnant adultsSignsTachycardia, murmur (in presence of anemia)Tongue depapillation, cheilosis, koilonychia (spoon nails), diffuse nonscarring scalp alopeciaSymptomsFatigue, decreased quality of lifeDecreased cognitive functionRestless legs syndromePica or pagophagia (ice craving)Decreased exercise toleranceRisk factorsPhysiologic state Extreme exerciseBlood loss Inflammatory bowel disease Peptic ulcer disease, gastritis GI malignant neoplasms Blood donation, surgery Hereditary hemorrhagic telangiectasia Hookworm or parasitic infectionLow iron intake Restricted diet (including vegan or vegetarian)Reduced absorption Gastric bypass surgery Gastroesophageal reflux disease or gastritis Helicobacter pylori infection Long-term use of proton pump inhibitor or antacid Celiac disease Bariatric surgical procedureGI, gastrointestinal.

Remarks:•For people with signs or symptoms associated with iron deficiency or ongoing iron deficiency risk factors (Table 1), a serum ferritin threshold of ≤50 ng/mL is appropriate to diagnose iron deficiency and guide management decisions.•This threshold is for adults without known or suspected inflammation. A separate recommendation was made for adults with inflammation (see recommendation 5).

Diagnosis of iron deficiency in menstruating individuals

Recommendation 3

For menstruating individuals, the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL and suggests against using a serum ferritin threshold of ≤15 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).

Remark:•For people with heavy menstrual bleeding (HMB) or other forms of abnormal uterine bleeding (AUB) resulting in excessive blood loss, symptoms associated with iron deficiency, additional risk factors for iron deficiency (Table 1), upcoming surgery, or planning pregnancy, a serum ferritin threshold of ≤50 ng/mL is appropriate to diagnose iron deficiency and guide management decisions.

Good practice statement

A detailed menstrual history is necessary to facilitate the diagnosis of AUB, particularly HMB. It would be essential to address abnormal bleeding menstrual and/or HMB, if identified.

Diagnosis of iron deficiency in pregnant individuals

Recommendation 4

For pregnant individuals, the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯) and recommends against using a serum ferritin threshold of ≤15 ng/mL for the diagnosis of iron deficiency (strong recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Table 2.Pregnancy-specific risk factors associated with iron deficiency during the perinatal periodPreceding history of HMBTeenage pregnancyHyperemesis gravidarumMultiple gestationVaginal bleeding after the first trimesterAbnormal placentation (placenta previa, placenta accreta spectrum, placental abruption)Short interpregnancy interval (<18 months between delivery and subsequent conception)Multiparity

Remark:•For pregnant individuals with anemia with or without other iron deficiency risk factors and/or symptoms associated with iron deficiency (Table 2), a serum ferritin threshold of ≤50 ng/mL may be appropriate to diagnose iron deficiency and guide management decisions.

Diagnosis of iron deficiency in adults with inflammation

Recommendation 5

For adults with anemia of inflammation, the ASH guideline panel suggests performing both serum ferritin and transferrin saturation (TSAT) rather than serum ferritin alone to evaluate for iron deficiency (conditional recommendation based on very low certainty in the evidence about effects ⨁◯◯◯).

Remarks:•Inflammation is on a continuum, and establishing a serum ferritin threshold for the diagnosis of iron deficiency is challenging. However, in adults with anemia of inflammation, the diagnosis of iron deficiency may be considered when (1) TSAT is <20% or (2) serum ferritin is <100 ng/mL.•TSAT should be drawn in a fasting state (5-9 hours,6 including fasting from multivitamin or iron supplements) because the test is susceptible to recent dietary intake.•Anemia of inflammation may occur in individuals with inflammatory bowel disease, infectious diseases, cancer, chronic kidney disease, heart failure, rheumatologic disorders, and other inflammatory disorders.•Because of a lack of data on the diagnosis of iron deficiency in children with inflammation, no recommendations were made for this population (see recommendation 1).

Good practice statement

Anemia of inflammation may be present concurrently with other causes of anemia. Consequently, for individuals with inflammation, serum ferritin and TSAT should be analyzed in the context of the full clinical picture, including consideration of the history, physical exam, underlying disease process, and other existing management guidelines7,8 for chronic diseases. Such guidelines may consider higher serum ferritin and/or TSAT thresholds for the diagnosis of iron deficiency.

These recommendations place the highest value on identifying individuals with iron deficiency to promote access to care and timely interventions. Outcomes affected by the timely diagnosis of iron deficiency (Table 3) were considered important by the panel for clinical decision-making across questions. Recommendations also take into consideration the values and preferences of affected populations, cost and cost-effectiveness, resource requirements, impact on health equity, acceptability, and feasibility.

Figure 2 illustrates all 5 diagnostic recommendations and associated remarks.Table 3.Outcomes affected by the timely diagnosis of iron deficiency that were considered by the panel for clinical decision-making across different populationsPopulationOutcomesAllSymptoms Cognitive function Fatigue Health-related quality of life Mental health, emotional lability Physical activity, shortness of breath, and/or cardiovascular health Pica Restless legs syndrome and/or periodic limb movement disorder Dermatologic healthTreatment Red cell transfusionPregnantMaternal Preterm delivery Postpartum hemorrhageFetal Fetal cognitive development Fetal iron deficiency Low birth weight Premature birthTreatment-related Oral iron Gastrointestinal adverse events IV iron Infusion site reactions Infusion reaction, not life-threatening and life-threatening Systemic infectionFigure 2.Algorithm of diagnostic recommendations. ID, iron deficiency. Figure created with biorender.com.

May J. (2026) https://biorender.com/ubqesi2.

Introduction

Aims of these guidelines and specific objectives

The purpose of these guidelines is to provide evidence-based recommendations on the diagnosis of iron deficiency that will improve the accurate identification of affected individuals and minimize harms of overdiagnosis. Through improved provider and patient education using available evidence and evidence-based recommendations, these guidelines aim to provide clinical decision support for shared decision-making that will result in better recognition of iron deficiency, which will lead to the identification and management of underlying etiology where applicable, improved counseling of affected individuals, and early initiation of iron therapy to improve iron status.

The target audience includes hematologists, family physicians, pediatricians, obstetricians and gynecologists, internists, other clinicians, and health care providers, including advanced practice providers, decision-makers, and patients. These guidelines may be relevant to policymakers engaged in developing local, national, or international initiatives that seek to enhance guidance on screening at-risk populations for iron deficiency and to implement standardized clinical decision limits (CDLs) in laboratory reporting. This document may also serve as the basis for adaptation by local, regional, or national guideline panels.

Description of the health problem

Iron is a critical micronutrient that serves key functions throughout the body, including erythropoiesis, DNA replication, mitochondrial energy production, and neurotransmitter synthesis. Despite its countless physiologic roles, iron deficiency is common and affects individuals across the life span in a variety of settings. Iron deficiency is associated with fatigue and poorer health-related quality of life, among other important patient-reported outcomes.

When underrecognized and untreated, iron deficiency progresses to iron deficiency anemia, the most common hematologic condition worldwide. Iron deficiency with or without anemia occurs when there is a net negative balance between iron intake and absorption and iron demands and losses. This imbalance may occur in the setting of insufficient dietary iron, increased iron needs (rapid growth or pregnancy), blood loss (including menstrual blood loss or losses within the gastrointestinal tract), and decreased iron absorption (eg, inflammatory states).

The most affected populations include young children and menstruating individuals, largely adolescent girls and adult women, especially during pregnancy. Individuals with underlying gastrointestinal disorders, bleeding disorders, and other chronic comorbid conditions are commonly affected by iron deficiency as well. Because of nonmedical drivers of health, individuals of economically disadvantaged backgrounds and/or within certain racial and ethnic minority groups are disproportionately affected.

Despite its prevalence, there is wide variation in the iron parameters used to diagnose iron deficiency. The lack of standardization as well as laboratory reference ranges that include values within a deficient range leads to underdiagnosis of iron deficiency, with subsequent delay in the receipt of readily available and effective iron therapies.

Methods

The guideline panel developed and graded the recommendations and assessed the certainty in the supporting evidence following the GRADE approach.3 The overall guideline development process, including funding of the work, panel formation, management of conflicts of interest, internal and external review, and organizational approval, was guided by the ASH policies and procedures intended to meet recommendations for trustworthy guidelines by the Institute of Medicine and the Guidelines International Network.1,9,10

Organization, panel composition, planning, and coordination

The work of this panel was coordinated by ASH and the University of Kansas Health System (funded by ASH under a paid agreement). Project oversight was provided by the ASH Guideline Oversight Subcommittee, which reports to the ASH Committee on Quality. ASH vetted and appointed individuals to the guideline panel.

The University of Kansas Health System vetted and retained researchers to conduct systematic reviews of evidence and coordinate the guideline development process, including the use of the GRADE approach. The membership of the panel and the systematic review team is described in supplemental 1.

The panel included adult and pediatric hematologists, 1 maternal fetal medicine specialist, 1 neonatologist, and 1 pharmacist, who all had clinical and research expertise on the guideline topic, as well as 1 patient representative. Several panel members had additional expertise and skills, including implementation science, cost-effectiveness, transfusion medicine, and laboratory medicine. One cochair was a content expert; the other was an expert in guideline development methodology.

Excluding the methodology team, all panelists were full and equal voting members for all recommendations.

In addition to synthesizing evidence systematically, the University of Kansas Health System supported the guideline development process, including determining methods, preparing meeting materials, and facilitating panel discussions. The panel’s work was performed using web-based tools (www.surveymonkey.com and www.gradepro.org) and face-to-face and online meetings.

Guideline funding and management of conflicts of interest

Development of these guidelines was wholly funded by ASH, a nonprofit medical specialty society that represents hematologists. Most members of the guideline panel were members of ASH. ASH staff supported panel appointments and coordinated meetings but had no role in choosing the guideline questions or determining the recommendations.

Members of the guideline panel received travel reimbursement for attendance at in-person meetings. Through the University of Kansas Health System, some researchers who contributed to the systematic evidence reviews received salary or grant support. Other researchers participated to fulfill the requirements of an academic degree or program.

Conflicts of interest of all panel members were managed according to ASH policies based on the recommendations of the Institute of Medicine (2011) and the Guidelines International Network.10 Panel members disclosed all financial and nonfinancial interests relevant to the guideline topic. ASH staff and the ASH Guideline Oversight Subcommittee reviewed the disclosures and composed the guideline panel to include a diversity of expertise and perspectives and avoid most panel having the same or similar conflicts. Greatest attention was given to direct financial conflicts with for-profit health care companies that could be directly affected by the guidelines.

Most guideline panel, including the cochairs, had no such conflicts. None of the University of Kansas Health System researchers who contributed to the systematic evidence reviews or who supported the guideline development process had any such conflicts. Many panelists had relevant nonfinancial interests, such as published opinions on the guideline topic.

Supplemental 2 provides the complete disclosure-of-interest forms of all panel members. In part A of the forms, individuals disclosed direct financial interests for 2 years before appointment; in part B, indirect financial interests; and in part C, relevant other interests that are not mainly financial. Part D describes new interests disclosed by individuals after appointment.

Part E summarizes ASH decisions about which interests were judged to be conflicts and how they were managed, including through recusal.

Supplemental 3 provides the complete disclosure-of-interest forms of the researchers who contributed to these guidelines.

Formulating specific clinical questions and determining outcomes of interest

The panel used the GRADEpro Guideline Development Tool (www.gradepro.org)11 to brainstorm and then prioritize questions, with the final selected questions listed here.1.Should a serum ferritin threshold of ≤12 ng/mL or ≤20 ng/mL be used to diagnose iron deficiency with or without anemia in children aged 9 months to 4 years?2.Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency with or without anemia in the adult population (excluding menstruating and pregnant individuals)?3.Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency with or without anemia in menstruating individuals?4.Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency with or without anemia in pregnant individuals?5.Should serum ferritin alone vs serum ferritin with TSAT be used to diagnose iron deficiency with or without anemia for the general population (including pediatrics and adults of all age groups) with inflammation?

The panel selected outcomes of interest for each question a priori, following the approach described in detail elsewhere.3 In brief, the panel first brainstormed all possible outcomes before rating their relative importance for decision-making following the GRADE approach.3

Given the lack of direct evidence assessing the impact of using different serum ferritin diagnostic thresholds on patient-important outcomes, the panel relied primarily on test accuracy data. The panel believed that the accuracy of different serum ferritin thresholds would not differ for the adult population, menstruating individuals, and pregnant individuals. Hence, the same systematic review data for test accuracy informed all 3 of these populations.

Separate diagnostic test accuracy data were used to inform guidance on infants and young children. Separate test accuracy data were also captured to inform the population with inflammation.

In contrast to diagnostic test accuracy, the panel believed that the prevalence of iron deficiency would vary considerably among the different populations. For that reason, the methods team conducted separate systematic reviews on the prevalence of iron deficiency in young children, adults (nonmenstruating, nonpregnant), menstruating individuals (adolescent and adult), and pregnant individuals. Targeted searches were also performed to inform the potential impact of the diagnosis, and anticipated treatment, of iron deficiency on different patient-important outcomes.

For pregnant individuals, this included data on the potential impact on both the pregnant individual and the fetus.

Serum ferritin as a diagnostic test

In considering diagnostic tests for iron deficiency, the panel weighed many available measures of iron status. Given that serum ferritin is widely available, commonly assessed, and considered the best indirect measure of total body iron stores, the panel prioritized this test in considering diagnostic questions. Serum ferritin is an acute-phase reactant and is ideally tested during an individual’s baseline state of health.

In healthy individuals without evidence of acute infection or chronic disease, serum ferritin is an accurate marker of iron status and, when low, is diagnostic of iron deficiency. However, existing laboratory serum ferritin reference intervals in both pediatric and adult populations are biased toward lower values. This issue occurred because the studies that informed such reference ranges included “apparently healthy individuals,” without considering that a portion of such individuals were iron deficient.12 As a result, clinical use of methodologically flawed serum ferritin lower limits of normal has contributed to underdiagnosis of iron deficiency and variations in its management.

The development of accessible and readily interpretable diagnostic laboratory thresholds facilitates prompt and equitable care. For all these reasons, the panel prioritized the identification of appropriate serum ferritin thresholds for the diagnosis of iron deficiency.

The panel acknowledges several limitations of serum ferritin testing, which include variability across laboratory methods for testing serum ferritin and lack of harmonization across platforms. Testing methods have evolved and include nonradiometric immunoassays, such as enzyme-linked immunoassay, chemiluminescent microparticle immunoassay, chemiluminescent assays, and electrochemiluminescence immunoassay, as well as radiometric assays, such as radioimmunoassays and immunoradiometric assays. As a result, different laboratory assays may obtain and report different serum ferritin values on the same serum sample.

This assay-to-assay variability occurs across the range of serum ferritin values but is most pronounced, and potentially clinically significant, at the higher end of serum ferritin values.13, 14, 15

A systematic review and meta-analysis on performance and comparability of laboratory methods for measuring serum ferritin concentrations in human serum or plasma found that, overall, laboratory methods had comparable accuracy and performance based on linearity between compared methods; however, there were limited studies that reported on the agreement between testing methods.13,16 Several studies have found poor agreement (bias from −11.5 to 44 ng/mL and standard deviation >25 ng/mL) between assays in nonpregnant women and children.14 Another study showed that serum ferritin results were consistently 36% to 44% higher with 1 type of assay over another in individuals with chronic kidney disease.15 Quality data from the Institute for Quality Management in Healthcare in Canada assessed 97 laboratories that included commonly used serum ferritin reagent kits and instruments globally to understand laboratory management of serum ferritin reference intervals. Postanalytical reporting showed a difference from the all-methods-mean results at the low end of serum ferritin (ie, <50 ng/mL) of ±30% to 40%, which means that for a serum ferritin of 10 ng/mL, the potential range across laboratories would be 7 to 14 ng/mL. For a serum ferritin of 30 ng/mL, the range across laboratories would be 21 to 42 ng/mL.

This interlaboratory variation suggests that an approximation approach to serum ferritin CDLs for the diagnosis of iron deficiency is appropriate, and this was considered by the panel when evaluating different serum ferritin thresholds (Institute for Quality Management in Healthcare, Proficiency Testing Endocrinology Program Data, ENDO-2202-Q).

Need to convert from LLN to a CDL for serum ferritin

The panel also noted that, for all populations, many community and hospital laboratories across all income settings use a laboratory-defined serum ferritin lower limit of normal (LLN) rather than a CDL for serum ferritin. The use of an LLN results in a significant variation in reference ranges between laboratories and the classification of values consistent with iron deficiency as within the reference range, both of which contribute to underrecognition of iron deficiency by ordering providers. In contrast, use of a CDL would mean that the laboratory would flag results at or below a clinically relevant diagnostic threshold as abnormal, regardless of the reference range.

Use of a CDL would allow health care providers to more accurately identify iron deficiency in lieu of currently used population-based reference ranges.

The panel suggested that community and hospital laboratories across all income settings convert from a laboratory-defined LLN to a CDL for the recommended serum ferritin thresholds. Flagging results at or below this threshold as abnormal would facilitate health care providers’ ability to diagnose iron deficiency compared to currently used population-based reference ranges. The panel further suggested that a comment accompany the postanalytical test report to facilitate guideline implementation.

Selection of serum ferritin thresholds for comparison

Regarding the selection of serum ferritin thresholds to compare for the diagnosis of iron deficiency, the panel considered indirect evidence that evaluated the physiologic effects of serum ferritin thresholds, recommendations from other organizations, as well as the panel’s expert consensus. The threshold of ≤15 ng/mL was considered by the panel predominantly based on the World Health Organization (WHO)–recommended serum ferritin threshold of <15 ng/mL for the diagnosis of iron deficiency in apparently healthy individuals.17 The serum ferritin threshold of ≤30 ng/mL was assessed based on a systematic review of guideline recommendations on numerous populations18 and a cross-sectional study from the US National Health and Nutrition Examination Surveys estimating the serum ferritin concentration at which the hemoglobin concentration plateaus and soluble transferrin receptor (sTfR) concentration begins to increase (sTfR minimum point).19 In this study, among nonpregnant women of reproductive age, a hemoglobin plateau occurred at a serum ferritin of 25.2 ng/mL (95% confidence interval, 24.2-26.2), and the sTfR minimum point occurred at a serum ferritin of 24.0 ng/mL (95% confidence interval, 23.3-24.6).19 The serum ferritin threshold of ≤50 ng/mL was evaluated based on a systematic review of guideline recommendations18 as well as physiologic data on iron absorption20 and correlation between levels of serum ferritin and hepcidin.21

Comparison of different serum ferritin thresholds in young children vs adult populations

The panel considered lower serum ferritin thresholds for young children relative to other populations, specifically considering a serum ferritin threshold of ≤12 ng/mL, because this threshold is recommended by WHO,17 to ≤20 ng/mL, based on physiologic studies on iron status in children.19 Assigning a lower diagnostic serum ferritin threshold in children, however, does not imply that iron needs for children are less or that children are resistant to iron deficiency. In fact, based on body weight (milligrams per kilogram), the iron requirements of children are substantially higher than those for adults.22 This greater need is attributable to iron demands for growth and expansion of red cell mass. If sufficient iron is available to meet these needs, the lower iron stores in children are not problematic but do mean that children are vulnerable to become iron deficient in settings of low dietary iron or blood loss.

Compared with children and adolescents, and in the absence of menstruation or pregnancy, adults have greater iron stores relative to iron use, which is reflected in higher serum ferritin levels. In such settings of high physiologic demand, iron is mobilized from ferritin stores into the circulation due at least in part to erythroid signals that modulate the hepcidin-ferroportin axis.23 Because erythropoietic activity is comparatively lower in adults, relatively more iron is retained as ferritin. Serum ferritin thresholds should be interpreted relative to the specific individual to which they are being applied, with an emphasis on ensuring that iron needs are met.

Bone marrow iron staining as the diagnostic reference standard for iron deficiency

To assess the diagnostic test accuracy of serum ferritin, a reference diagnostic gold standard was needed for comparison. The panel considered many available tests that assess iron status to define iron deficiency, including assessment of other iron parameters, response to oral iron therapy, and the historical reference standard of bone marrow aspirate iron staining examination. Based on the review of existing literature by the methodology team, the guideline panel members agreed that bone marrow aspirate iron staining was the primary standard for which sufficient published data for the proposed analysis exist.

Most of the diagnostic test accuracy data for serum ferritin in diagnosing iron deficiency (assessed by sensitivity and specificity) were determined using published data as compared to bone marrow aspirate iron staining. One additional study that used a TSAT ≤20% as a reference standard for iron deficiency was also reviewed and included in diagnostic test accuracy data.24

Although marrow examination for the sole purpose of assessing iron stores is now rarely justifiable, absent or very low stainable marrow iron was historically the most broadly accepted standard to identify iron deficiency.25 The panel acknowledges its limitations, such as bone marrow specimen sampling bias, subjectivity in grading, and unclear correlation with functionally available total body iron stores.26, 27, 28, 29

The reliability of marrow iron assessment by Perls Prussian blue staining depends on the adequacy of the specimen, including the presence of bone spicules, and may be limited in many samples.26 Iron assessment is semiquantitative, using ordinal scales with subjectivity in distinguishing between iron deficiency (either absent or grade 1 staining) and iron sufficiency (≥grade 2).27,30 In infants and young children, stainable iron can be absent from shortly after birth until the first year of life and may be very low thereafter through the fourth year of life.31 In addition, iron stored in marrow reticular cells and macrophages might not necessarily reflect iron available to developing erythroblasts.25,28 The relationship between marrow iron and the iron status of other tissues vulnerable to deficiency has not been systematically investigated, and using the bone marrow as a reference standard places emphasis on iron’s role in erythropoiesis without fully appreciating the effects of iron status on other critical cellular processes throughout the body. Functional iron deficiency or iron-restricted erythropoiesis, for example, occurs when there is iron present in the body but unavailable for use because of systemic inflammatory effects. In such individuals, bone marrow iron may not be an adequate reflection of iron status.

In persons with inflammation, the panel considered separate diagnostic test accuracy data to inform the diagnostic recommendation for iron deficiency.

Recognizing these limitations, our analyses provided a means of comparing preselected serum ferritin thresholds for the best combination of sensitivity and specificity to identify iron deficiency, at least as defined by bone marrow iron staining. The caveats with this definition were among many considerations in ultimately assigning recommended serum ferritin thresholds for clinical use.

Evidence review and development of recommendations

For each guideline question, the University of Kansas Health System prepared a GRADE “Evidence-to-Decision” (EtD) framework using the GRADEpro Guideline Development Tool (www.gradepro.org).32, 33, 34 The EtD table summarized the results of systematic reviews of the literature that were performed for this guideline. The EtD table addressed the desirable and undesirable effects of testing options (different serum ferritin thresholds), values and preferences (relative importance of outcomes), certainty in the evidence, resource use (cost-effectiveness), equity, acceptability, and feasibility. The guideline panel reviewed draft EtD tables during the guideline panel meeting and made suggestions for corrections.

The panel also identified missing indirect evidence to inform the impact and consequences of using different serum ferritin thresholds as they relate to patient-important outcomes. To ensure that recent studies were not missed, searches (presented in supplemental 4) were updated in July 2025. Panel members were asked to suggest any studies that fulfilled the inclusion criteria for the individual questions that may have been missed in the searches.

Under the direction of the University of Kansas Health System, researchers followed the general methods outlined in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (https://www.cochrane.org/authors/handbooks-and-manuals/handbook-systematic-reviews-diagnostic-test-accuracy). Risk of bias was assessed at the health outcome level using the quality assessment of diagnostic accuracy studies QUADAS-2 and QUADAS-C. In addition to conducting systematic reviews of diagnostic test accuracy, the researchers searched for evidence related to prevalence and baseline risks, values, preferences, and costs and summarized findings within the EtD frameworks.32, 33, 34 Subsequently, certainty in the body of evidence (also known as quality of the evidence or confidence in the estimated effects) was assessed for outcomes of interest following the GRADE approach based on the following domains: risk of bias, precision, consistency and magnitude of the estimates of effects, directness of the evidence, and risk of publication bias.

Certainty was categorized into 4 levels ranging from very low to high.3 Within this report, these categories are represented by symbols, as described in Figure 3.Figure 3.Certainty in the evidence.

Interested readers may find more explanation about the GRADE approach to assessing and rating certainty in a body of evidence in other publications.3

During a 2-day in-person meeting followed by online communication and conference calls, the panel developed clinical recommendations based on the evidence summarized in the EtD tables. For each recommendation, the panel took a population perspective and came to consensus on the following: the certainty in the evidence, the balance of benefits and harms of the different testing options (serum ferritin threshold), and the assumptions about the associated values and preferences. The guideline panel also considered the potential for additional investigations as well as resource use (iron therapy, health care use) associated with a higher number of individuals being diagnosed with iron deficiency.

The panel agreed on the recommendations (including direction and strength), remarks, and qualifications by consensus or, in rare instances, by voting (an 80% majority was required for a strong recommendation), based on the balance of all desirable and undesirable consequences. The specific wording for each recommendation was intentional. The final guidelines, including recommendations, were reviewed and approved by all members of the panel.

Document review

Draft recommendations were reviewed by all members of the panel, revised, and then made available online on 29 September 2025 for external review by stakeholders, including allied organizations, other medical professionals, patients, and the public. Thirty-nine individuals or organizations submitted comments. The document was revised to address pertinent comments and modify remarks for clarity, but no changes were made to recommendations.

On 22 April 2026, the ASH Guideline Oversight Subcommittee and the ASH Committee on Quality approved that the defined guideline development process was followed, and on 28 April 2026, the officers of the ASH Executive Committee approved the submission of the guidelines for publication under the imprimatur of ASH. The guidelines were then subjected to peer review by Blood Advances.

How to use these guidelines

ASH guidelines are primarily intended to help clinicians and patients make shared decisions about diagnostic and treatment alternatives, with the goal of improving quality of patient care. Other purposes are to inform policy, education, and advocacy and to state future research needs. These guidelines are not intended to serve or be construed as a standard of care.

Clinicians must make decisions based on the clinical presentation of each individual patient, ideally through a shared process that considers the patient’s values and preferences with respect to the anticipated outcomes of the chosen option.

Decisions may be constrained by the realities of a specific clinical setting and local resources, including, but not limited to, institutional policies, time limitations, or availability of treatments.

Policymakers, including payers, may use these guidelines to inform decisions about the allocation of health care resources, for example, coverage decisions. Such decisions should be consistent with the intended interpretation of strong and conditional recommendations (Figure 1). For example, it would be a misinterpretation of these guidelines to deny or restrict access to an intervention based on the direction or strength of a recommendation or based on certainty in the evidence supporting the recommendation.

It is the position of ASH that patients should have access to all safe and effective treatment options recommended by the individual patient’s physician.35,36

These guidelines may not include all appropriate methods of care for the clinical scenarios described. As science advances and new evidence becomes available, recommendations may become outdated. Following these guidelines cannot guarantee successful outcomes.

ASH does not warrant or guarantee any products described in these guidelines.

Statements about the underlying values and preferences, as well as qualifying remarks accompanying each recommendation, are its integral parts and serve to facilitate more accurate interpretation. They should never be omitted when quoting or translating recommendations from these guidelines. The use of these guidelines is also facilitated by links to the EtD frameworks and the interactive summary of findings tables, found in the “Summary of the evidence for each recommendation” section.

Recommendations

Diagnosis of iron deficiency in children

Should a serum ferritin threshold of ≤12 ng/mL or ≤20 ng/mL be used to diagnose iron deficiency with or without anemia in children aged 9 months to 4 years?Recommendation 1For infants and children aged 9 months to 4 years, the ASH guideline panel suggests using a serum ferritin threshold of ≤20 ng/mL instead of a threshold of ≤12 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Remarks:•This threshold is for infants and children without known or suspected inflammation, and a higher serum ferritin threshold may be required for children with inflammation.•Because of a lack of direct evidence, specific recommendations for children aged >4 years until adolescence (defined as age ≥11 years5 as per AAP) and nonmenstruating adolescents were not developed. For children aged >4 years until adolescence, a serum ferritin threshold of ≤20 ng/mL is appropriate for the diagnosis of iron deficiency by indirectly applying evidence for young children. For nonmenstruating adolescents, a serum ferritin threshold of ≤30 ng/mL is appropriate for the diagnosis of iron deficiency by indirectly applying evidence from menstruating adolescents and adult populations.•For menstruating adolescents, please see recommendation 3.

Summary of the evidence

Evidence for the diagnostic test accuracy included 1 observational study (n = 87) with a median age of 36.5 months (interquartile range, 17.1 months). The study compared a serum ferritin threshold of <12 ng/mL vs <18 ng/mL (which was used to inform the threshold of 20 ng/mL).37 For a serum ferritin threshold of ≤12 ng/mL, the pooled sensitivity and specificity were 0.44 and 0.90, respectively, and for a serum ferritin threshold of ≤20 ng/mL, these were 0.74 and 0.77, respectively.

The systematic review on the prevalence of iron deficiency included 56 studies (n = 121 394). The pooled estimate for the global prevalence of iron deficiency in this population was 30% (L. Lopes, M.

Azzam, Q. Hamarsha, et al, unpublished data, April 2025).

Four observational studies also provided indirect evidence through estimation of physiologically based serum ferritin thresholds for this age group.19,38, 39, 40Supplemental 5 provides the evidence profile and EtD framework for recommendation 1.

Benefits

The accurate diagnosis of iron deficiency in children allows for prompt intervention (dietary counseling, iron supplementation) to prevent the progression of iron deficiency to iron deficiency anemia or, in individuals with iron deficiency anemia, to more severe anemia. The benefits of identifying and treating iron deficiency in children are particularly significant because of the high iron demands in development and the demonstrated improvement in hematologic parameters,41 cognition, and neurodevelopment42,43 with supplementation.

The panel prioritized a serum ferritin threshold that maximized true positives and minimized false negatives based on the expected benefit of identification of a great number of patients with iron deficiency who may benefit from treatment. The panel suggests the serum ferritin threshold of ≤20 ng/mL independent of concomitant signs or symptoms of iron deficiency.

Harms and burdens

The panel placed greater value on not missing the diagnosis of iron deficiency in children (false negatives) over incorrectly identifying children as iron deficient (false positives), given that a missed diagnosis may lead to adverse health consequences, including poor neurodevelopment, worse cognition,44,45 as well as increased fatigue and decreased physical performance in older children and adolescents.46,47 The panel determined that the undesirable effects of a lower serum ferritin threshold of ≤12 ng/mL were greater than those of ≤20 ng/mL because of a higher number of false negatives, given how missed diagnosis of iron deficiency may result in a prolongation of unaddressed negative health issues. In contrast, those incorrectly identified as iron deficient may experience adverse effects from unnecessary iron supplementation (most commonly gastrointestinal side effects) with limited benefits. IV iron, although less commonly used in this age group, poses a small risk of infusion reactions (see “Harms and burdens” under “Recommendation 2” for additional discussion of the undesirable effects of iron supplementation).

The harms related to the administration of iron therapy and follow-up laboratory evaluation in false positives may be more significant in young children than in other populations. The panel recognized that children in malaria-endemic areas may be more vulnerable to harm with unnecessary iron supplementation, specifically in settings in which malaria prevention or management services are unavailable.48

Other EtD criteria and considerations

With the implementation of a higher ferritin threshold, more children will be diagnosed with iron deficiency. The panel considered that this could have effects on public health and health equity, discussed in detail in “Other EtD criteria and considerations” for recommendation 2. The panel recognized that some stakeholders may be concerned about the challenges of treating more children; however, ≥1 acceptability survey of health care providers (n = 155) found that the majority (81%) did not have concerns about increasing diagnostic threshold.49 The panel also recognized that a higher diagnostic threshold would likely lead to additional laboratory testing and subsequent follow-up appointments, which may not be consistently accessible for all children.

Conclusions and research needs for this recommendation

The guideline panel suggests using a serum ferritin threshold of ≤20 ng/mL instead of a serum ferritin threshold of ≤12 ng/mL to diagnose iron deficiency in children aged between 9 months and 4 years despite a low certainty in the evidence. This conditional recommendation was developed based on the body of available direct and indirect evidence with consideration of net health benefits and harms, cost-effectiveness, acceptability, feasibility, and health equity.

This higher threshold will result in a higher proportion of children with iron deficiency receiving a diagnosis and potentially benefitting from appropriate evaluation and management. The panel preferred the higher threshold (≤20 ng/mL) for the higher sensitivity (better ability to correctly identify children with iron deficiency) despite a lower specificity because of the potential negative consequences of missing a diagnosis of iron deficiency in this age group. Consideration of the undesirable effects of false positives included the potential harms of iron therapy as well as the potential harms of follow-up testing.

Based on available data, there is a low certainty in the evidence regarding the effects of the use of a higher diagnostic threshold on children's health outcomes. However, this lack of certainty is likely due, in part, to a lack of research into the impact of therapy on such outcomes and does not imply that such effects do not exist.

The panel identified the following additional research needs and questions for children:1.Prevalence of iron deficiency in children aged >4 years until adolescence and in nonmenstruating adolescents.2.Assessment of changes in serum ferritin and TSAT values across all pediatric age groups from birth to adulthood.3.Evaluation of outcomes related to screening at various serum ferritin thresholds for iron deficiency in young children and impact of treatment on such outcomes.4.Stakeholder engagement to evaluate the acceptability, feasibility, and health state utility values of different serum ferritin thresholds. Stakeholders include patients, caregivers, physicians, and other pediatric health care providers.5.Randomized clinical trials comparing health outcomes in children when treated based on different serum ferritin thresholds.6.Cost-effectiveness studies comparing the diagnosis and downstream implications of testing and treatment at different serum ferritin thresholds.7.Exploration of the health equity implications of different serum ferritin thresholds for pediatric individuals, including those living in malaria-endemic areas.

Diagnosis of iron deficiency in adults (excluding menstruating or pregnant individuals)

Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency with or without anemia in the adult population (excluding menstruating and pregnant individuals)?Recommendation 2For the adult population (excluding menstruating or pregnant individuals), the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL instead of ≤15 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Remarks:•For people with signs or symptoms associated with iron deficiency or ongoing iron deficiency risk factors (Table 1), a serum ferritin threshold of ≤50 ng/mL is appropriate to diagnose iron deficiency and guide management decisions.•This threshold is for adults without known or suspected inflammation. A separate recommendation is made for adults with inflammation (see recommendation 5).

Summary of the evidence

Evidence for the diagnostic test accuracy included a total of 17 cross-sectional studies24,50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65 (5327 individuals); 13 studies included both male and female adults, 1 included only menstruating individuals, and 3 included only pregnant individuals. All but 1 of the included studies used serum ferritin (at thresholds of 15, 30, or 50 ng/mL) as the index test and bone marrow examination (absent or reduced Perls Prussian blue staining) as a reference standard to confirm the diagnosis of iron deficiency. One additional study used TSAT (≤21%) as a reference standard for the diagnosis of iron deficiency.24 For the serum ferritin cutoff of ≤15 ng/mL, the pooled sensitivity and specificity were 0.41 and 0.99, respectively.

For a serum ferritin threshold of ≤30 ng/mL, the pooled sensitivity and specificity were 0.67 and 0.96, respectively; for a serum ferritin threshold of ≤50 ng/mL, the pooled sensitivity and specificity were 0.89 and 0.86, respectively.

The systematic review of the prevalence of iron deficiency in adults (nonmenstruating, nonpregnant) included 52 studies (n = 154 819 individuals). The pooled estimate for the global prevalence of iron deficiency in this population was 16% (Q. Harmasha, H.

Kawtharany, M. Azzam, et al, unpublished data, April 2025). Supplemental 6 provides the evidence profile and EtD framework for recommendation 2.

Benefits

The accurate diagnosis of iron deficiency in adults allows for prompt iron supplementation to prevent the progression of iron deficiency to iron deficiency anemia or, in individuals with iron deficiency anemia, to more severe anemia. The benefits of identifying and treating iron deficiency in adults66, 67, 68 include improvement in symptoms, such as fatigue, impaired cognition, pica, emotional lability,66, 67, 68, 69 restless legs syndrome, the need for blood transfusion,70 physical performance, and overall health-related quality of life, even if nonanemic.71,72

The panel prioritized a serum ferritin threshold that maximized true positives and minimized false negatives based on the expected benefit of identification of a great number of patients with iron deficiency who may benefit from treatment.

Harms and burden

The panel placed greater value on not missing the diagnosis of iron deficiency (false negatives) over incorrectly identifying individuals as iron deficient (false positives), given that a missed diagnosis may lead to adverse health consequences, including symptoms of fatigue, impaired cognition, and decreased physical performance, which negatively affect overall quality of life. The panel determined that the undesirable effects of the lowest serum ferritin threshold of ≤15 ng/mL were greater than in the higher serum ferritin thresholds, given a missed diagnosis of iron deficiency may result in a prolongation of unaddressed negative health issues. The panel determined that the undesirable effects of the highest serum ferritin threshold of ≤50 ng/mL were also significant because those incorrectly identified as iron deficient may experience adverse effects from unnecessary evaluation (ie, bidirectional endoscopy) and/or iron supplementation with limited benefit.

The panel determined that the serum ferritin threshold of ≤30 ng/mL best balanced the number of false negatives and false positives and, consequently, had the lowest degree of undesirable effects. The panel recognized that different individuals may place greater weight on different types of undesirable effects (unnecessary testing vs failure to be diagnosed and receive treatment). Finally, some panel members emphasized that bidirectional endoscopy may be more critical in the setting of anemia rather than iron deficiency alone.

Regarding the potential undesirable adverse effects of iron therapy, oral iron supplementation may lead to gastrointestinal side effects. Undesirable adverse events of IV iron include infusion reactions. A systematic review and meta-analysis of oral iron, IV iron, and no iron found that, overall, IV iron was not associated with an increased risk of serious adverse events or infections.73,74 Although there is low certainty in the estimate of the risk of adverse effects because of imprecision and inconsistency, given available evidence, the guideline panel considered the risk of adverse effects from iron therapy to be small.75

Other EtD criteria and considerations

The panel acknowledged that there is a significant variation between patients with iron deficiency and their associated symptoms at different serum ferritin thresholds, which creates important certainty or variability in patient values.

The feasibility of serum ferritin testing does not differ based on thresholds, and the test is widely available. A 2024 study of health care providers from 23 countries found that 100% of respondents reported using serum ferritin testing in clinical practice.76 The panel recognized that some stakeholders may be concerned about the challenges of treating more patients with iron deficiency based on new diagnostic thresholds; however, ≥1 acceptability survey of health care providers (n = 155) found that the majority (81%) did not have concerns about increasing diagnostic threshold.49 For those who were concerned, 31 (32%) indicated that a cutoff of ≤30 ng/mL was too low and would lead to underdiagnosis. The panel recommends early stakeholder engagement and targeted knowledge translation with implementation of new thresholds.

Finally, although the direct cost of the serum ferritin test will not differ according to the use of different diagnostic thresholds for iron deficiency, the substantial variability globally in the cost associated with serum ferritin testing was acknowledged.

Although there is no direct evidence on the impact of different serum ferritin thresholds on health equity, using a higher threshold will identify more individuals with iron deficiency. Identifying more individuals with iron deficiency with inadequate access to care may indirectly enhance equity by promoting efforts to improve treatment access for marginalized groups (by influencing insurance coverage options, health policy advocacy, or provider willingness to treat). On the other hand, the panel acknowledged that higher thresholds may also have adverse effects on equity by increasing the financial burden on individuals and health systems.

The panel also expressed concerns about using a higher threshold in malaria-endemic regions because of the risk of worsening infection for patients with uncontrolled malaria who are started on iron therapy. In malaria-endemic settings, the relationship between iron status and serum ferritin levels is complex, as is also the relationship between iron status and risk for malarial infection. However, the panel acknowledged that in the context of treatment, iron therapy would be appropriate and beneficial.

The impact of different ferritin thresholds in the context of these settings is unknown. Given these considerations, despite the lack of evidence, the panel posited that the overall impact on health equity using a higher serum ferritin threshold would be “probably increased.”

Conclusions and research needs for this recommendation

The guideline panel suggests a serum ferritin threshold of ≤30 ng/mL over a serum ferritin threshold of ≤15 ng/mL to diagnose iron deficiency for the general adult population (excluding menstruating or pregnant individuals) despite a low certainty in the evidence. This conditional recommendation was developed based on the body of available direct and indirect evidence with consideration of net health benefits and harms, cost-effectiveness, acceptability, feasibility, and health equity.

This higher threshold will result in a higher proportion of adults with iron deficiency receiving a diagnosis and potentially benefitting from appropriate evaluation and management. The panel preferred the higher threshold (≤30 ng/mL) for the higher sensitivity (better ability to correctly identify patients with iron deficiency) despite a lower specificity because of the potential negative consequences of missing a diagnosis of iron deficiency. Consideration of the undesirable effects of false positives included the potential harms of iron therapy as well as the potential use of endoscopic evaluation to identify the cause of iron deficiency.

The low certainty in the evidence and the limited published evidence evaluating the impact of serum ferritin diagnostic thresholds on clinical outcomes influenced the strength of the recommendation. However, this low certainty is likely attributable in part to a lack of research into the impact of therapy on such outcomes and does not imply that such effects do not exist.

The panel identified the following additional research needs and questions for adults:1.Studies focused on an appropriate reference standard for iron deficiency as well as the harmonization of serum ferritin laboratory testing across platforms and/or reagents.2.Stakeholder engagement to assess the perspectives of patients, physicians, and other health care providers on the feasibility, acceptability, and health state utility implications, measured directly (time trade-off, standard gamble) or indirectly (EuroQol 5-Dimension [EQ-5D] questionnaire), of different serum ferritin thresholds (15, 30, and 50 ng/mL) and to evaluate the association between untreated vs treated iron deficiency (with and without anemia) and related health state utilities.3.Randomized clinical trials comparing patient-important outcomes using different serum ferritin diagnostic thresholds to guide iron therapy in adults with iron deficiency.4.Cost-effectiveness studies comparing diagnosis at different serum ferritin diagnostic thresholds, including the higher threshold of 50 ng/mL, with an assessment of the magnitude and impact of the need for additional evaluations (ie, colonoscopy) with the higher serum ferritin thresholds.5.Exploration of health equity implications for different serum ferritin diagnostic thresholds in adults.6.Impact of higher serum ferritin thresholds on individuals in malaria-endemic regions, including approach to prevention, diagnosis, and treatment of iron deficiency in such settings.

Diagnosis of iron deficiency in menstruating individuals

Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency in menstruating individuals?Recommendation 3For menstruating individuals, the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL and suggests against using a serum ferritin threshold of ≤15 ng/mL for the diagnosis of iron deficiency (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Remark:•For people with HMB or other forms of AUB resulting in excessive blood loss, symptoms associated with iron deficiency, additional risk factors for iron deficiency (Table 1), upcoming surgery, or planning pregnancy, a serum ferritin threshold of ≤50 ng/mL is appropriate to diagnose iron deficiency and guide management decisions.Good practice statementA detailed menstrual history is necessary to facilitate the diagnosis of AUB, particularly HMB. It would be essential to address abnormal menstrual bleeding and/or HMB, if identified.

Summary of the evidence

The same diagnostic test accuracy data were used to inform the recommendations for the adult, menstruating, and pregnant populations as described in “Summary of the evidence” under “Recommendation 2.”

The systematic review on the prevalence of iron deficiency in menstruating individuals included 79 studies (n = 264 178 individuals) and was composed of menstruating individuals between the ages of 12 and 45 years. The pooled estimate for the global prevalence of iron deficiency in this population was 27% (A. Choaib, J.

Khawandi, Q. Hamarsha, et al, unpublished data, May 2025).

In addition, 5 observational studies,77, 78, 79, 80, 81 12 randomized controlled trials,82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 2 meta-analyses,68,94 2 systematic reviews,95,96 and 1 Cochrane review97 informed an estimation of the effect of different serum ferritin thresholds on treatment decisions and the resulting impact on patient-important outcomes. Supplemental 7 provides the evidence profile and EtD framework for recommendation 3.

Benefits

Defining a diagnostic serum ferritin threshold for iron deficiency is of great importance to guide further diagnostic evaluation and access to treatments, particularly for medically underserved populations at greater risk of iron deficiency.98 The accurate diagnosis of iron deficiency in menstruating individuals allows for prompt iron supplementation to prevent the progression of iron deficiency to iron deficiency anemia or, in individuals with iron deficiency anemia, to more severe anemia. The benefits of identifying and treating iron deficiency in menstruating individuals were assumed to include those demonstrated in the adult population (see “Benefits” under “Recommendation 2”), with additional benefits. Iron repletion in menstruating individuals that become pregnant may derive the additional benefit of avoiding iron deficiency in pregnancy.

The panel judged that a serum ferritin threshold of ≤30 ng/mL was a feasible threshold to implement across all income settings. However, the panel supported the use of a serum ferritin threshold of ≤50 ng/mL in subgroups of menstruating people, recognizing those with HMB as a particularly vulnerable subgroup.99

The panel prioritized a serum ferritin threshold that maximized true positives and minimized false negatives based on the expected benefit of identification of a great number of patients with iron deficiency who may benefit from treatment.

Harms and burdens

The panel placed greater value on not missing the diagnosis of iron deficiency (false negatives) over incorrectly identifying individuals as iron deficient (false positives), given that a missed diagnosis may lead to adverse health consequences. In menstruating individuals, these consequences include risk of progressive iron deficiency and anemia, major bleeding at gynecologic surgery, blood transfusion and red cell antigen alloimmunization (potentially complicating future pregnancies), fatigue, impaired cognition, altered mood, poor physical performance, and decreased health-related quality of life. The panel determined that the undesirable effects of a serum ferritin threshold of ≤15 ng/mL were highest because of the high proportion of those with HMB in this population as well as the high risk of blood transfusion among those undergoing gynecologic surgeries.100

The panel further considered indirect evidence demonstrating cost-effectiveness of use of a serum ferritin threshold ≤25 ng/mL for women of reproductive age, recognizing that serum ferritin of 25 vs 30 ng/mL may be interchangeable because of laboratory assay variability.101 Although a diagnostic threshold of ≤50 ng/mL was probably favored, there was concern regarding the higher number of false positives with this threshold and the potential undesirable effects associated with unnecessary iron supplementation (see “Harms and burdens” under “Recommendation 2” for additional discussion of the undesirable effects of iron supplementation). In addition, the panel felt that most people with iron deficiency from menstrual blood loss have a serum ferritin far lower than 50 ng/mL at diagnosis.

Other EtD criteria and considerations

See “Other EtD criteria and considerations” under “Recommendation 2,” which are also relevant to this recommendation.

Conclusions and research needs for this recommendation

The guideline panel suggest using a serum ferritin threshold of ≤30 ng/mL and suggests against using a serum ferritin threshold of ≤15 ng/mL for the diagnosis of iron deficiency in menstruating individuals despite a low certainty in the evidence. This conditional recommendation was developed based on the body of available direct and indirect evidence with consideration of net health benefits and harms, cost-effectiveness, acceptability, feasibility, and health equity.

Using a higher serum ferritin threshold of ≤30 ng/mL instead of a lower serum ferritin threshold of ≤15 ng/mL in menstruating individuals reduces the risk of untreated iron deficiency and progression to iron deficiency anemia. In consideration of the threshold of ≤30 ng/mL compared with ≤50 ng/mL, the recommendation was influenced heavily by concerns about risk of false positives with ≤50 ng/mL, given the limited data on the impact on clinical outcomes. Overall, based on the body of available evidence, it is likely that the adoption of a diagnostic serum ferritin threshold of ≤30 ng/mL reduces the risk of undiagnosed and untreated iron deficiency among menstruating individuals.

As for the highest serum ferritin threshold of ≤50 ng/mL, the panel ultimately supported its use in certain subgroups of menstruating individuals given the potential desirable effects of earlier diagnosis, intervention, and the potential for symptomatic improvement in some.

The low certainty in the evidence and the limited published evidence evaluating the impact of serum ferritin diagnostic thresholds on clinical outcomes influenced the strength of the recommendation. However, this low certainty is likely attributable in part to a lack of research into the impact of therapy on such outcomes and does not imply that such effects do not exist.

The panel identified the following areas for additional research in menstruating people:1.Studies focused on an appropriate reference standard for iron deficiency, as well as the harmonization of serum ferritin laboratory testing across platforms and/or reagents.2.Evaluation of outcomes related to various serum ferritin diagnostic thresholds and the impact of treatment on such outcomes (including subgroups listed earlier).3.Stakeholder engagement to assess perspectives of patients, physicians, and other health care providers on the feasibility, acceptability, and health state utility implications, measured directly (time trade-off, standard gamble) or indirectly (EQ-5D), of different serum ferritin thresholds (15, 30, and 50 ng/mL) and to evaluate the association between untreated vs treated iron deficiency (with and without anemia) and related health state utilities.4.Randomized clinical trials comparing patient-important outcomes using different serum ferritin diagnostic thresholds to guide iron therapy in menstruating individuals5.Cost-effectiveness studies comparing diagnosis at different serum ferritin diagnostic thresholds, including the higher threshold of 50 ng/mL, in menstruating individuals (including subgroups listed earlier).6.Exploration of health equity implications for different serum ferritin diagnostic thresholds in menstruating individuals.

Diagnosis of iron deficiency in pregnant individuals

Should a serum ferritin threshold of ≤15 ng/mL, ≤30 ng/mL, or ≤50 ng/mL be used to diagnose iron deficiency in pregnant individuals?Recommendation 4For pregnant individuals, the ASH guideline panel suggests using a serum ferritin threshold of ≤30 ng/mL (conditional recommendation based on low certainty in the evidence about effects ⨁⨁◯◯) and recommends against using a serum ferritin threshold of ≤15 ng/mL for the diagnosis of iron deficiency (strong recommendation based on low certainty in the evidence about effects ⨁⨁◯◯).Remark:•For pregnant individuals with anemia with or without other iron deficiency risk factors and/or symptoms associated with iron deficiency (Table 2), a serum ferritin threshold of ≤50 ng/mL may be appropriate to diagnose iron deficiency and guide management decisions.

Summary of the evidence

The same diagnostic test accuracy data were used to inform the recommendations for the adult, menstruating, and pregnant populations, as described in the “Summary of the evidence” under “Recommendation 2.”

The systematic review on the prevalence of iron deficiency in pregnant individuals included 31 studies (n = 93 782 individuals) composed of pregnant individuals across all trimesters. The panel selected to use the average pooled estimate from all trimesters rather than prevalence data at a specific time point in pregnancy. Consequently, the pooled estimate for the global prevalence of iron deficiency in pregnant individuals was 37% (A.

Choaib, J. Khawandi, Q. Hamarsha, et al, unpublished data, May 2025).

Supplemental 8 provides the evidence profile and EtD framework for recommendation 4.

Benefits

The accurate diagnosis of iron deficiency during pregnancy allows for prompt iron supplementation to prevent the progression of iron deficiency to iron deficiency anemia or, in individuals with iron deficiency anemia, to more severe anemia. The panel prioritized a serum ferritin threshold that maximized true positives and minimized false negatives based on the expected benefit of identification of a great number of patients with iron deficiency who may benefit from treatment. Although relevant to all populations, the benefit of identifying and treating iron deficiency, irrespective of the presence or absence of anemia, is paramount in pregnant individuals because of the high iron demands of pregnancy and delivery19 and the associated improvement in both maternal and neonatal outcomes with iron supplementation.102, 103, 104, 105, 106 However, the panel also considered the lack of direct data comparing clinical outcomes using a diagnostic serum ferritin threshold of 30 ng/mL vs 50 ng/mL.

Harms and burdens

To determine the undesirable effects at each serum ferritin threshold, the panel weighed the number of false negatives and false positives, the potential adverse effects of iron supplementation, and the paucity of clinical outcome data to justify treatment initiation at the highest serum ferritin threshold of 50 ng/mL. The panel placed greater value on not missing the diagnosis of iron deficiency (false negatives) over incorrectly identifying individuals as iron deficient (false positives), given that a missed diagnosis may lead to adverse health consequences.

The panel determined that the undesirable effects of the lowest serum ferritin threshold of ≤15 ng/mL were greater than those of the higher thresholds, given a missed diagnosis of iron deficiency may result in a prolongation of unaddressed negative health issues. In contrast, those incorrectly identified as iron deficient may experience adverse effects from unnecessary supplementation (see “Harms and burdens” under “Recommendation 2” for additional discussion of the undesirable effects of iron supplementation). The panel noted that the side effects of oral iron supplementation may be amplified during pregnancy and acknowledged the time and financial burdens of IV iron.

The panel considered that data on the potential benefits and harms of iron supplementation at higher serum ferritin thresholds are mixed.107 Iron supplementation in the setting of maternal hemoglobin >13 g/dL was associated with preeclampsia and hypertensive disorders of pregnancy.108 Data on the benefits of iron administration at higher serum ferritin levels on cognitive outcomes in infants have also been mixed.109,110

Consequently, the panel determined that the serum ferritin threshold of ≤30 ng/mL best balanced the number of false negatives and false positives and, consequently, had the lowest degree of undesirable effects. The panel also recognized that different individuals may place greater weight on different types of undesirable effects (unnecessary supplementation vs failure to be diagnosed and receive treatment).

Other EtD criteria and considerations

See “Other EtD criteria and considerations” under “Recommendation 2,” which are also relevant to this recommendation.

Specific to the pregnant population, the certainty in the evidence was judged to be low because of the serious risk of bias and serious indirectness of included studies. Although data showed poorer maternal, neonatal, and fetal outcomes with lower serum ferritin, the panel acknowledged that there are no data that directly link maternal or neonatal outcomes to specific serum ferritin thresholds during pregnancy, much less in a specific trimester of pregnancy.103 The panel also discussed the impact of the serum ferritin diagnostic threshold on equity. Specifically, adopting a higher serum ferritin threshold may benefit individuals with limited health care access, enabling them to receive iron supplementation before the development of anemia, which may reduce disparities in maternal health in high-risk populations.111 Finally, the potential feasibility and implementation challenges of a higher serum ferritin threshold for the diagnosis of iron deficiency in this population were recognized.

Conclusions and research needs for this recommendation

The panel suggests using a serum ferritin threshold of ≤30 ng/mL and recommends against using a serum ferritin threshold of <15 ng/mL for the diagnosis of iron deficiency in pregnant people despite a low certainty in the evidence. This conditional recommendation was developed based on the body of available direct and indirect evidence with consideration of health benefits and harms regarding both maternal and neonatal outcomes, acceptability, feasibility, and health equity.

Using a higher serum ferritin threshold of ≤30 ng/mL instead of a lower serum ferritin threshold of ≤15 ng/mL, at any gestational age, reduces both the risk of untreated iron deficiency during pregnancy and the risk of progression to iron deficiency anemia. In consideration of the threshold of ≤30 ng/mL compared with ≤50 ng/mL, the recommendation was influenced heavily by concerns about the risk of false positives with the highest threshold of 50 ng/mL, given limited data on impact on maternal and fetal outcomes. Consideration of the undesirable effects of false positives included the potential harms of iron therapy and additional follow-up testing.

The panel supported the use of this highest threshold of ≤50 ng/mL in pregnant individuals with concomitant anemia, with the goal of minimizing progression of iron deficiency anemia in later trimesters, as well as reliance of the fetus on maternal iron stores. However, there were concerns about the feasibility of implementing this threshold. There was not unanimous support for the threshold of 50 ng/mL for pregnant individuals without anemia because of uncertain benefits and uncertain potential harms of treatment at this threshold.

The panel identified the following additional research questions on iron status assessment and diagnostic thresholds in pregnancy:1.Examination of the relationship between serum ferritin and TSAT in pregnant individuals across gestational stages and trimesters.2.Evaluation of outcomes related to serum ferritin testing in pregnancy, including the optimal timing (gestational age) for screening and treatment.3.Stakeholder engagement to assess perspectives of patients, physicians, and other obstetric health care providers on the feasibility, acceptability, and health state utility implications, measured directly (time trade-off, standard gamble) or indirectly (EQ-5D questionnaire), of different serum ferritin thresholds (15, 30, and 50 ng/mL) and to evaluate the association between untreated vs treated iron deficiency (with and without anemia) and related health state utilities.4.Randomized clinical trials and prospective comparison of patient-important outcomes using different serum ferritin diagnostic thresholds to guide iron therapy in pregnancy.5.Cost-effectiveness studies comparing diagnosis at different serum ferritin diagnostic thresholds in pregnancy.6.Exploration of health equity implications for different serum ferritin diagnostic thresholds on maternal and fetal outcomes.

Diagnosis of iron deficiency in adults with inflammation

Should serum ferritin alone vs serum ferritin with TSAT be used to diagnose iron deficiency with or without anemia in the general population (including pediatrics and adults of all age groups) with inflammation?Recommendation 5For adults with anemia of inflammation, the ASH guideline panel suggests performing both serum ferritin and TSAT rather than serum ferritin alone to evaluate for iron deficiency (conditional recommendation based on very low certainty in the evidence about effects ⨁◯◯◯).Remarks:•Inflammation is on a continuum, and establishing a serum ferritin threshold for the diagnosis of iron deficiency is challenging. However, in adults with anemia of inflammation, the diagnosis of iron deficiency may be considered when (1) TSAT <20% or (2) serum ferritin <100 ng/mL.•TSAT should be drawn in a fasting state (5-9 hours,6 including fasting from multivitamin or iron supplements) because the test is susceptible to recent dietary intake.•Anemia of inflammation may occur in individuals with inflammatory bowel disease, infectious diseases, cancer, chronic kidney disease, heart failure, rheumatologic disorders, and other inflammatory disorders.•Because of a lack of data on the diagnosis of iron deficiency in children with inflammation, no recommendations were made for this population (see recommendation 1).Good practice statementAnemia of inflammation may be present concurrently with other causes of anemia. Consequently, in individuals with inflammation, serum ferritin and TSAT should be analyzed in context of the full clinical picture, including consideration of the history, physical exam, underlying disease process, and other existing management guidelines7,8 for chronic diseases.

Such guidelines may consider higher serum ferritin and/or TSAT thresholds for the diagnosis of iron deficiency.

Summary of the evidence

Evidence for diagnostic test accuracy included 2 comparative cross-sectional studies of individuals (n = 67)112,113; 1 study included adults with heart failure, and 1 study included adults with renal failure. Both studies presented data on the sensitivity and specificity comparing serum ferritin alone vs performing both serum ferritin and TSAT. The pooled sensitivity and specificity for serum ferritin alone (<100 ng/mL) were 0.38 and 0.88, respectively.

For serum ferritin threshold <100 ng/mL and/or TSAT <20%, the pooled sensitivity and specificity were 0.91 and 0.70, respectively. Supplemental 9 provides the evidence profile and EtD framework for recommendation 5.

Benefits

The accurate diagnosis of iron deficiency in the setting of inflammation allows for the potential initiation of therapy to mitigate the negative consequences of iron deficiency, which include worsening of anemia and exacerbation of poorer outcomes related to the underlying comorbid condition and primary cause of inflammation. The diagnosis of absolute iron deficiency can be challenging in the presence of inflammation because serum ferritin may be falsely “normal” or “elevated” because it is an acute-phase reactant. Therefore, panel members considered assessment of serum ferritin alone as often insufficient to assess iron status in adults with inflammation and supported the use of multiple iron parameters to inform the diagnosis.

TSAT reflects circulating iron and identifies states of iron-restricted erythropoiesis, irrespective of the presence of inflammation, thereby providing additional information to inform the individual’s iron status.

The panel considered serum ferritin <100 ng/mL or TSAT <20% to be accurate for the diagnosis of iron deficiency for many, but not necessarily all, individuals in the setting of inflammation. The panel recognized that inflammation is a continuum and that dichotomous thresholds are limited in fully characterizing the spectrum and range of inflammation. Regardless, thresholds for diagnostic and treatment guidance were judged to be of moderate benefit to patients.

Harms and burden

To determine the undesirable effects of using serum ferritin alone vs serum ferritin or TSAT to make a diagnosis of iron deficiency in adults with inflammation, the panel considered false-positive and false-negative diagnoses. The panel considered the undesirable effects of unnecessary iron therapy in persons falsely identified to be deficient and the negative health consequences of missing the diagnosis of iron deficiency, which would include worse fatigue, impaired cognition, poorer health-related quality of life, and worse outcomes related to the comorbid illness (false negatives). The panel prioritized the desire to minimize false negatives and considered the undesirable effects of using serum ferritin ≤100 ng/mL alone to be moderate and those of using serum ferritin ≤100 ng/mL or TSAT <20% overall to be likely to be small.

Panel members expressed their willingness to give iron treatment when TSAT was ≤20% even if anemia might be because of iron-restricted erythropoiesis rather than absolute iron deficiency because of the potential for positive health benefits for both conditions.

Other EtD criteria and considerations

Certainty in the evidence of test accuracy was judged to be low because of concerns around the risk of bias and the use of indirect evidence. For instance, in evaluating management effects, the panel considered indirect evidence from 4 randomized controlled trials in individuals with iron deficiency and heart failure that defined iron deficiency as serum ferritin ≤100 ng/mL or TSAT <20%.85,114, 115, 116 All 4 trials showed consistent improvement in symptoms, with very few reported side effects. The panel acknowledged that because of the presence of chronic comorbid conditions and inflammation, although individuals may have improvement in symptoms with IV iron, resolution of anemia may not be complete (because of other contributing causes of anemia) even after treatment with IV iron.

The panel posits that most individuals would value being aware of having absolute or functional iron deficiency, although individuals may vary in their prioritization of receiving treatment for iron deficiency in the setting of other comorbidities. Despite variations in costs and charges of the laboratory tests, the panel considered the difference between serum ferritin alone and serum ferritin and TSAT to likely be of negligible costs and savings. The panel assessed the testing to likely be acceptable to patients and feasible for providers.

Given the difficulty of diagnosing absolute iron deficiency in individuals with inflammation, and acknowledging that inflammation is a continuum, a variety of tests have been proposed to supplement the diagnosis. These included the use of sTfR or markers of inflammation, such as sedimentation rate or C-reactive protein, to “adjust” serum ferritin threshold for inflammation. In reviewing these potential adjunctive tests, none had sufficient data to recommend their use as standalone tests, but they may be helpful in the full context of the individual’s clinical condition and other laboratory values.

Conclusions and research needs for this recommendation

The guideline panel suggests assessment of both serum ferritin and TSAT for the diagnosis of iron deficiency in adults with inflammation despite a low certainty in the evidence for a net health benefit and harm reduction.

Based on available evidence, serum ferritin of <100 ng/mL or TSAT <20% may identify many individuals with concomitant iron deficiency in the setting of inflammation, thereby reducing untreated iron deficiency and its attendant negative health consequences. Because of the low certainty in the evidence and the very limited number of prospective trials providing indirect evidence, a recommendation regarding specific thresholds was not made.

The panel identified the following additional research questions in individuals with inflammation:1.Studies on various iron parameters, including diagnostic hepcidin assays, to inform the diagnosis of iron deficiency in the setting of anemia of inflammation.2.Evaluation of the relationship between serum ferritin and TSAT in pediatrics, including the optimal threshold for diagnosing iron deficiency in children with concomitant inflammation.3.Randomized clinical trials that examine different iron parameters for the diagnosis of iron deficiency in individuals with inflammation to guide treatment and assess patient-important outcomes.

What are others saying, and what is new in these guidelines?

Guidance from the WHO recommends a serum ferritin threshold of <12 ng/mL for children and a threshold of <15 ng/mL for otherwise healthy adults.17 These thresholds are considered highly specific but have low sensitivity for the accurate diagnosis of individuals with iron deficiency. Evidence assessed by this guideline panel examined these specific ranges and identified low evidence to suggest the use of these thresholds in any population.

A new joint clinical report on iron deficiency and iron deficiency anemia from the AAP and the American Society of Pediatric Hematology/Oncology will provide diagnostic guidance for infants, children, and adolescents that is consistent with the serum ferritin thresholds developed in these ASH diagnostic guidelines. The American College of Obstetrics and Gynecology recommends a serum ferritin threshold of <30 ng/mL for the diagnosis of iron deficiency in pregnant people.117 The National Bleeding Disorder Foundation Medical and Scientific Advisory Council 2026 guidelines recommend a ferritin level of <50 ng/mL as the cutoff for diagnosing iron deficiency in males and females with inherited bleeding disorders at all ages.118

Call to action on screening

Recommendations on screening were out of scope of this diagnostic guideline because of the need to prioritize diagnostic thresholds to facilitate accurate diagnosis across populations. Therefore, an evidence-based review focused on screening for iron deficiency was not performed.

Since 2010, the AAP has recommended universal anemia screening in young children at the age of 12 months.119 A joint clinical report from the AAP and the American Society of Pediatric Hematology/Oncology published in 2026 recommends universal screening for both anemia and iron deficiency in all young children as well as all menstruating individuals after the onset of menarche.120 The National Bleeding Disorder Foundation Medical and Scientific Advisory Council 2026 guidelines include recommendations for screening all individuals with inherited bleeding disorders for iron deficiency and anemia.118 The American College of Obstetricians and Gynecologists does not currently recommend routine screening for iron deficiency during pregnancy.117 However, a body of evidence demonstrates the pervasiveness of iron deficiency (defined as serum ferritin <30 ng/mL) in pregnancy irrespective of the presence or absence of anemia.121 In addition to affecting maternal outcomes, iron deficiency has potential negative impacts on the developing fetus.43 The use of hemoglobin and mean corpuscular volume as surrogates for iron sufficiency is inaccurate,122 and literature demonstrates positive effects of early iron repletion in nonanemic pregnant individuals.123, 124, 125 Based on the preceding statements, the panel believes it is reasonable to screen for iron deficiency by checking serum ferritin in all pregnant individuals as well as other high-risk populations with or without concomitant anemia.

Limitations of these guidelines

The limitations of these guidelines are inherent in the low or very low certainty in the evidence we identified for many of the questions.

Revision or adaptation of the guidelines

Plans for updating these guidelines

After publication of these guidelines, ASH will maintain them through surveillance for new evidence, ongoing review by experts, and regular revisions.

Updating or adapting recommendations locally

Although a global perspective was taken in the development of this guideline, adaptation of these guidelines will be necessary in many circumstances. These adaptations should be based on the associated EtD frameworks.126

Conflict-of-interest disclosure: All authors were members of the guideline panel or the systematic review team or both. As such, they completed a disclosure-of-interest form, which was reviewed by the American Society of Hematology and is available as supplementals 2 and 3.