Diagnostic Criteria for Iron Deficiency Anemia
Diagnose iron deficiency anemia using a ferritin cutoff of <45 ng/mL in patients without inflammation, and consider ferritin up to 100 ng/mL as consistent with iron deficiency in the presence of active inflammation. 1
Laboratory Diagnosis
In Patients Without Inflammation
- Serum ferritin <30 ng/mL is the single most powerful diagnostic test for iron deficiency 1
- The 2020 AGA guideline recommends using ferritin <45 ng/mL as the diagnostic threshold (strong recommendation, high-quality evidence) 1
- Transferrin saturation <20% supports the diagnosis 1
- Microcytic anemia (low MCV) and hypochromic red cells are characteristic but may be absent in combined deficiencies 1
In Patients With Inflammation or Chronic Disease
- Ferritin up to 100 ng/mL may still indicate iron deficiency when inflammation is present 1
- In inflammatory bowel disease specifically, ferritin 30-100 ng/mL suggests combined iron deficiency and anemia of chronic disease 1
- Transferrin saturation <16-20% helps confirm iron deficiency in this context 1
Confirmatory Testing
- A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even with equivocal iron studies 1
- Complete blood count should include MCV, mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) 1
- MCH may be more sensitive than MCV for detecting iron deficiency as it is less affected by storage conditions 1
Treatment Approach
Oral Iron Therapy (First-Line for Most Patients)
Prescribe oral iron as first-line treatment for patients with mild anemia, clinically inactive disease, and no prior intolerance to oral iron. 1
Dosing
- 100-200 mg elemental iron daily (or 325 mg ferrous sulfate daily, which contains 65 mg elemental iron) 2, 3
- Administer between meals for optimal absorption 1
- Alternate-day dosing may improve tolerability with similar efficacy 4
- Continue treatment for 2-3 months after hemoglobin normalization to replenish iron stores 1
When Oral Iron is Appropriate
- Mild anemia (hemoglobin >100 g/L) 1
- Clinically inactive disease without inflammation 1
- No previous intolerance to oral iron 1
- Adequate gastrointestinal absorption capacity 3
Intravenous Iron Therapy (First-Line in Specific Situations)
Use intravenous iron as first-line treatment for patients with clinically active inflammatory bowel disease, hemoglobin <100 g/L, previous oral iron intolerance, or conditions requiring erythropoiesis-stimulating agents. 1
Specific Indications for IV Iron
- Clinically active inflammatory bowel disease 1
- Hemoglobin <100 g/L 1
- Previous intolerance to oral iron 1
- Malabsorption conditions (celiac disease, atrophic gastritis, post-bariatric surgery) 3, 4
- Chronic kidney disease 4
- Heart failure 4
- Second and third trimesters of pregnancy 4
- Ongoing blood loss 4
- Need for erythropoiesis-stimulating agents 1
Evidence for IV Iron Superiority
- In inflammatory bowel disease, IV iron demonstrates higher efficacy (OR 1.57 for achieving 2 g/dL hemoglobin rise) and faster response compared to oral iron 1
- Lower treatment discontinuation rates due to adverse events (OR 0.27) 1
- Fewer gastrointestinal side effects compared to oral iron 1
Gastrointestinal Evaluation
Bidirectional Endoscopy Recommendations
Perform bidirectional endoscopy (gastroscopy and colonoscopy) in asymptomatic postmenopausal women and men with iron deficiency anemia. 1
Strong Indications
- All postmenopausal women and men with iron deficiency anemia (strong recommendation, moderate evidence) 1
- Risk of gastrointestinal malignancy justifies endoscopic evaluation 1
Conditional Indications
- Premenopausal women with iron deficiency anemia (conditional recommendation, moderate evidence) 1
- Young patients with plausible alternative causes may reasonably defer initial endoscopy in favor of iron replacement trial 1
- Premenopausal women <40 years may not require bidirectional endoscopy initially 3
Additional Gastrointestinal Testing
Celiac Disease Screening
- Perform serologic testing first (transglutaminase antibody IgA with total IgA) 1, 3
- Small bowel biopsy only if serology is positive (conditional recommendation) 1
- Celiac disease causes 2-3% of iron deficiency anemia cases 1
Helicobacter pylori Testing
- Non-invasive testing followed by treatment if positive (conditional recommendation, low evidence) 1
- Consider in patients with suspected atrophic gastritis 1
Small Bowel Investigation
- Not routinely recommended after negative bidirectional endoscopy 3
- Perform capsule endoscopy or CT/MRI enterography only with red flags: involuntary weight loss, abdominal pain, elevated CRP, or persistent iron deficiency despite treatment 3
Common Pitfalls and Caveats
Ferritin Interpretation Errors
- Do not use ferritin <15 ng/mL as the sole cutoff—the AGA strongly recommends 45 ng/mL for improved sensitivity 1
- Ferritin is an acute phase reactant; levels >100 ng/mL do not exclude iron deficiency in inflammatory conditions 1
- Always assess C-reactive protein or other inflammatory markers when interpreting ferritin 1
Premature Discontinuation of Treatment
- Continue oral iron for 2-3 months after hemoglobin normalization to replenish stores 1
- In inflammatory bowel disease, reinitiate IV iron when ferritin drops below 100 ng/mL or hemoglobin falls below 120-130 g/L (gender-dependent) 1
Overlooking Malabsorption
- Screen for celiac disease even in asymptomatic patients—it is a well-recognized cause of iron deficiency anemia 1
- Consider atrophic gastritis, especially in elderly patients or those with H. pylori infection 1
Assuming Dietary Deficiency
- A positive dietary history should not be presumed as the sole cause—full gastrointestinal investigation is still required 1
- Borderline deficient diets are common but rarely the only explanation 1