In a new Annals “Beyond the Guidelines” feature, two hematologists and coauthors of the 2025 Iron Consortium Guideline published in Lancet Hematology discuss how to diagnose, evaluate, and manage iron deficiency and iron deficiency anemia (IDA) in a patient whose symptoms and test results fall into areas of clinical uncertainty. Their discussion highlights differences in approach to testing thresholds, the role of gastrointestinal evaluation, and when to use oral versus intravenous (IV) iron, drawing on recent guidelines and evolving evidence.
They reviewed the case of Ms. B, a 35-year-old woman referred for evaluation after routine blood work showed small red blood cells and low iron levels but only mild anemia. Further testing confirmed iron deficiency, and she reported increasingly heavy menstrual periods. Despite a year of oral iron therapy, her iron levels did not improve as expected, and IV iron was recommended.
The first discussant, Kylee L. Martens, MD, is an Assistant Professor of Medicine and a member of the Division of Hematology & Medical Oncology at Oregon Health & Science University. Dr. Martens emphasizes that iron deficiency can be clinically significant even without anemia and may be missed if clinicians focus only on hemoglobin levels. She highlights ferritin as the most useful test but notes ongoing debate about the best cutoff values. Dr. Martens underscores the importance of assessing menstrual blood loss and suggests a low threshold for further evaluation, including gastrointestinal testing when the cause is unclear. She favors earlier use of IV iron, especially in patients with ongoing blood loss. Dr. Martens recommends a detailed menstrual history with a low threshold for bidirectional endoscopy, as well as prompt treatment with IV iron.
The second discussant, Jason A. Freed, MD, is an Assistant Professor of Medicine at Harvard Medical School and a member of the Division of Hematology and Hematologic Malignancies at Beth Israel Deaconess Medical Center. Dr. Freed agrees that no single test or cutoff definitively diagnoses IDA and recommends considering the full clinical picture, including symptoms, lab trends, and patient history. He places greater emphasis on starting with oral iron, which is inexpensive and effective for many patients, with reassessment after several weeks to ensure response. Dr. Freed suggests reserving IV iron for those who do not respond or cannot tolerate oral therapy. Dr. Freed recommends testing Ms. B for celiac disease, managing her heavy menstrual bleeding, and trialing oral iron for 4 to 6 weeks with a plan to transition to IV iron if necessary.
Both experts stress the importance of identifying and addressing the underlying cause of iron deficiency, particularly heavy menstrual bleeding, and tailoring treatment to the individual patient. They agree that clearer diagnostic thresholds and better approaches to evaluating common causes like menstrual blood loss remain important gaps in current guidelines.
All “Beyond the Guidelines” features are based on selected clinical conferences at Beth Israel Deaconess Medical Center (BIDMC) and include multimedia components published in Annals of Internal Medicine.
Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact one of the discussants, please email Kendra McKinnon at kmckinn1@bidmc.harvard.edu.
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