Iron-deficiency anemia is extremely common worldwide, and a gastrointestinal cause should be considered in all patients without an obvious etiology. The American Gastroenterological Association (AGA) recently published clinical practice guidelines on the gastrointestinal evaluation of iron-deficiency anemia using an evidence-based approach in Gastroenterology.1

Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, the AGA Institute’s Clinical Guidelines Committee developed these recommendations for the diagnosis of iron-deficiency anemia and the initial gastrointestinal evaluation of chronic iron-deficiency anemia based on the strength of available evidence, patient preferences and values, risks and benefits of different management pathways, and resource use.1 They were submitted to the AGA Governing Board accompanied by a technical review that provided a detailed synthesis of the evidence from which these recommendations were formulated and approved.2 Below is an executive summary of the AGA’s recommendations for gastrointestinal evaluation of iron-deficiency anemia.1

In patients with anemia, the AGA recommends using a cutoff of 45 ng/mL over 15 ng/mL when using ferritin to diagnose iron deficiency (strength of recommendation: strong; quality of evidence: high). Guideline authors note that in patients with chronic inflammatory conditions or chronic kidney disease, ferritin levels may not be an accurate representation of body iron stores. Among these patients, the use of additional laboratory tests — such as C-reactive protein, transferrin saturation, or soluble transferrin saturation — may be necessary to diagnose iron-deficiency anemia.


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In asymptomatic postmenopausal women and men with iron-deficiency anemia, the AGA recommends bidirectional endoscopy over no endoscopy (strength of recommendation: strong; quality of evidence: moderate).

In asymptomatic premenopausal women with iron-deficiency anemia, the AGA suggests bidirectional endoscopy over iron replacement therapy only (strength of recommendation: conditional; quality of evidence: moderate). Clinicians should discuss with patients the tradeoff between “very small risks” associated with deferred bidirectional endoscopy vs the small risks of endoscopy in this patient population. Patients who feel strongly about avoiding endoscopy-associated risks may choose initial iron replacement therapy without an initial bidirectional endoscopy.

In patients with iron-deficiency anemia without other identifiable etiology after bidirectional endoscopy, the AGA suggests noninvasive testing for Helicobacter pylori, followed by treatment if positive, over no testing (strength of recommendation: conditional; quality of evidence: low).

In patients with iron-deficiency anemia, the AGA suggests against the use of routine gastric biopsies to diagnose atrophic gastritis (strength of recommendation: conditional; quality of evidence: very low).

In asymptomatic adult patients with iron-deficiency anemia and plausible celiac disease, the AGA suggests initial serologic testing, followed by small bowel biopsy only if positive, over routine small bowel biopsies (strength of recommendation: conditional; quality of evidence: very low). Even in asymptomatic patients, celiac disease is a well-recognized cause of iron-deficiency anemia. Clinicians should consider this as a differential diagnosis.

In uncomplicated asymptomatic patients with iron-deficiency anemia and negative bidirectional endoscopy, the AGA suggests a trial of initial iron supplementation over the routine use of video capsule endoscopy (strength of recommendation: conditional; quality of evidence: very low). Clinicians should apply caution when treating patients with comorbid conditions, in whom the identification of small bowel pathology may change medication management, including the use of anticoagulation or antiplatelet therapies.

Several gaps in current knowledge were identified, including the outcomes and proper techniques of small bowel investigation in patients with negative bidirectional endoscopy.1 However, all clinical guidelines are reviewed annually at the AGA Clinical Guideline Committee meeting, and the next update for these guidelines is anticipated to occur in 3 years (2023).

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References

1. Ko CW, Siddique SM, Patel A, et al. AGA clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anemia [published online August 15, 2020]. Gastroenterology. doi: 10.1053/j.gastro.2020.06.046

2. Rockey DC, Altayar O, Falck-Ytter Y, Kalmaz D. AGA technical review on the gastrointestinal evaluation of iron deficiency anemia [published online August 20, 2020]. Gastroenterology. doi: 10.1053/j.gastro.2020.06.045