7 Takeaways From the AGA's New Iron-Deficiency Anemia Guidelines

David A. Johnson, MD


September 18, 2020

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Iron deficiency is a commonly encountered clinical scenario among gastroenterologists performing endoscopy and colonoscopy. The American Gastroenterological Association (AGA) has just issued new guidelines on the gastrointestinal evaluation of iron-deficiency anemia that give us pragmatic, evidence-based recommendations, several of which I believe to have practice-changing implications. Therefore, I want to highlight some of the key take-home messages from these well-written guidelines.

Iron deficiency is a fairly prevalent condition. Estimates from a decade ago indicate that iron deficiency had an approximately 3% prevalence rate in North America. Normal, ongoing iron losses of 1-2 mg a day occur due to exfoliation of the skin or the intestinal tract, minor blood loss, and other factors, but typically this doesn't result in iron deficiency.

The AGA's guidelines made several important recommendations, the first of which set a new definition for iron deficiency in patients with anemia. The authors recommended that the threshold level for ferritin be changed from 15 ng/mL to 45 ng/mL. They rated this as a strong recommendation based on high-quality evidence.

This was done to account for ferritin's changing sensitivity. Ferritin is a phase reactant, meaning it elevates in the presence of certain inflammatory or disease-related conditions. The authors noted that a ferritin value of < 15 ng/mL has a sensitivity for detecting iron deficiency of only 59%, but the sensitivity rises to 85% when you set the threshold at < 45 ng/mL. This doesn't require a tremendous trade-off in terms of specificity, which is 99% for < 15 ng/mL and 92% for < 45 ng/mL.

The second recommendation, which was rated as strong with moderate-quality evidence supporting it, calls for bidirectional endoscopy over no endoscopy in asymptomatic postmenopausal women and in men with iron-deficiency anemia.

As detailed in a technical review that accompanied the guidelines, pooled estimates from 18 studies on the diagnostic yield of bidirectional endoscopy in these populations revealed that it detected lower and upper intestinal malignancy in approximately 9% and 2% of patients, respectively. The authors did point out, however, that there is stratification bias in these estimates due to the inclusion of both symptomatic and asymptomatic patients, so it doesn't necessarily reflect the true prevalence. But nonetheless, the prevalence was high enough to suggest that we perform bidirectional endoscopy, especially as the risk of doing so is quite low.

They also extended a recommendation for bidirectional endoscopy over iron replacement therapy to premenopausal women, so long as there are no mitigating circumstances such as excessive menstrual losses. However, they tempered this slightly by categorizing it as a conditional recommendation supported by moderate-quality evidence.

In the next recommendation, the authors suggested following bidirectional endoscopy with noninvasive testing (eg, serologic testing) for Helicobacter pylori, with treatment for those determined to be positive. This was categorized as a conditional recommendation based on low-quality evidence.

The accompanying technical review featured a pooled analysis of three randomized controlled studies which showed that, after endoscopy, patients tested for H pylori [and treated if positive, in addition to iron replacement] experienced improved hemoglobin compared with those who received iron replacement alone. Noninvasive testing is cost-effective if the bidirectional endoscopy is negative.

The AGA guidelines' authors recommended against performing routine biopsies for atrophic gastritis in patients with iron-deficiency anemia. This was given a conditional recommendation based on low-quality evidence.

The next recommendation, which was conditional and based upon very low-quality evidence, dealt with advanced testing for serologic evidence of celiac disease, a prevalent cause of iron-deficiency anemia. The authors suggested reserving biopsies of the duodenum to asymptomatic adult patients with iron-deficiency anemia who are determined to be positive upon serologic testing, rather than performing random biopsies.

The authors noted that there are particular considerations to keep in mind when assessing risk, such as the relatively low prevalence of celiac disease in certain patient populations, such as those in East Asian countries (eg, Japan, China). Conversely, there is a heightened likelihood for celiac disease among patients with a personal history of autoimmune diseases (eg, type 1 diabetes) or gastrointestinal symptoms. Otherwise, serologic testing should be performed before bidirectional endoscopy and followed by biopsies if positive.

The AGA's final recommendation was that a trial of iron supplementation is preferred over the routine performance of video capsule endoscopy in uncomplicated asymptomatic patients with iron-deficiency anemia and negative bidirectional endoscopy. This was a conditional recommendation based on very low-quality evidence.

The authors noted that there are exceptions to applying this recommendation, such as ongoing evidence of overt bleeding, patients hospitalized for anemia, or comorbid conditions that would change the medical management, in particular with anticoagulation or antiplatelet therapy. Therefore, the recommendation again is to not jump to capsule endoscopy unless there is something potentially driving the risk profile.

These new AGA guidelines are exceptionally well done. I hope this serves you well the next time you face an iron deficiency evaluation. It certainly changed my practice.

Thanks again for listening. I look forward to chatting with you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

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