PITTSBURGH — Clinical management guidelines from the American Gastroenterological Association (AGA) in 2020 sought to standardize iron deficiency anemia (IDA) management. Among the recommendations was that men and postmenopausal women with asymptomatic IDA undergo esophagogastroduodenoscopy and colonoscopy (bidirectional endoscopy) and that, conditionally, the same management should be used for premenopausal women with asymptomatic IDA.
To enhance sensitivity, the guidelines liberalized the diagnostic threshold for iron deficiency from serum ferritin ≤ 15 ng/mL, as recommended by the World Health Organization (WHO), to ≤ 45 ng/mL, according to the authors of a recent research letter published in the American Journal of Hematology.1
The researchers from the University of Pittsburgh and the University of Pennsylvania schools of medicine, as well as the VA Pittsburgh Healthcare System, pointed out that, in draft guidelines released in September 2025, the American Society of Hematology (ASH) suggested a liberalized ferritin threshold at an intermediate value of ≤ 30 ng/mL based on low certainty of evidence.
“We recently reported that, compared with the ferritin ≤ 15 ng/mL threshold, the ≤ 30 and ≤ 45 ng/mL thresholds increase the number of individuals in the United States classified as having IDA by 2.4 and 3.3 million, respectively,” the authors wrote. “However, the impact of these new ferritin thresholds on the distribution of iron deficiency risk factors among individuals with IDA is unknown. “
To assess the impact, they conducted a cross‐sectional study utilizing data from the 2017-2020 cycle of the National Health and Nutrition Examination Survey (NHANES), which is the first nationwide survey in the United States to assess iron status among premenopausal women, postmenopausal women and men since the 1990s. Using the data, the study team characterized gastrointestinal and dietary risk factors for iron deficiency among individuals classified as having IDA across ferritin thresholds from the WHO, ASH and the AGA.
The research identified 7,357 nonpregnant adults, representing 213.7 million (95% confidence interval, CI 195.5-232.0 million) individuals in the U.S. population. Of these, 58.2 million were premenopausal women (95% CI 51.2-65.3 million), 55.8 million were postmenopausal women (95% CI 50.0-61.6 million), and 99.7 million were men (95% CI 91.1-108.4 million).
The findings include that, overall, 5.9 (95% CI 4.7-7.1), 8.3 (95% CI, 6.8-9.9) and 9.2 million (95% CI 7.6–10.7 million) individuals were classified as having IDA at the ferritin ≤ 15, ≤ 30 and ≤ 45 ng/mL thresholds, respectively. At the ferritin ≤ 30 ng/mL threshold, 1.3 million (57%) individuals newly classified to have IDA were premenopausal women. At the ferritin ≤ 45 ng/mL threshold, 1.7 million (53%) individuals newly classified to have IDA were premenopausal women.
“We assessed gastrointestinal bleeding risk factors as comorbidities and prescription medications associated with increased risk of gastrointestinal hemorrhage,” the authors advised. “At the ferritin ≤ 15 ng/mL threshold, 0.7 million individuals (95% CI 0.4-1.0 million) with IDA had gastrointestinal bleeding risk factors. Liberalizing the ferritin threshold to ≤ 30 ng/mL did not statistically significantly increase the total number of individuals with gastrointestinal bleeding risk factors classified as having IDA (0.7 million, 95% CI 0.0-1.2 million), but liberalizing the ferritin threshold to ≤ 45 ng/mL did (1.0 million, 95% CI 0.3-1.8 million). “
Subgroup analyses found that both thresholds classified more postmenopausal women and men with gastrointestinal bleeding risk factors as having IDA compared with the ≤ 15 ng/mL threshold (incremental counts.
“In summary,” the authors advised, “this nationally representative cross‐sectional study demonstrates that the AGA’s recommendation to liberalize the serum ferritin threshold used to diagnose iron deficiency from ≤ 15 to ≤ 45 ng/mL classifies 0.8 million more postmenopausal women and 0.6 million more men as having IDA and that most of these individuals have conditions associated with gastrointestinal iron loss. This indicates that a liberalized ferritin threshold has the potential to identify individuals with pathological iron deficiency risk factors earlier in their disease course.
“However, identifying these individuals is at the expense of classifying 1.7 million more premenopausal women as having IDA, with 76% of these individuals having insufficient dietary iron intake that could be treated with iron supplementation. Coupled with a recommendation from the AGA to pursue bidirectional endoscopy for patients with asymptomatic IDA, these findings indicate that liberalizing the threshold to diagnose iron deficiency from ferritin ≤ 15 to ≤ 45 ng/mL could lead to over‐utilization of endoscopy and patient burden, especially for premenopausal women. Additionally, we demonstrate that the ferritin ≤ 30 ng/mL threshold being considered by ASH results in similar distributions of iron deficiency risk factors among individuals classified as having IDA compared with the AGA’s ≤ 45 ng/mL threshold.”
- Al Ta’ani O, Mayrer BM, Luche NM, Siddique SM, Peslak SA, Anderson TS, Vajravelu RK. Distribution of Gastrointestinal and Dietary Risk Factors Among U.S. Adults Classified as Having Iron Deficiency Anemia Across Diagnostic Thresholds. Am J Hematol. 2026 Aug;101(8):2095-2099. doi: 10.1002/ajh.70388. Epub 2026 May 30. PMID: 42218567; PMCID: PMC13331639.