What are the diagnostic criteria and management options for iron deficiency in patients, particularly those with high-risk demographics such as menstruating or pregnant women?

Diagnostic Criteria for Iron Deficiency

Iron deficiency is diagnosed by hemoglobin below 13 g/dL in men or below 12 g/dL in non-pregnant women, combined with serum ferritin <45 ng/mL, though ferritin <15 ng/mL is highly specific for absolute iron deficiency. 1

Laboratory Diagnostic Thresholds

Hemoglobin Criteria

• Men: Hb <13 g/dL (130 g/L) 1
• Non-pregnant women: Hb <12 g/dL (120 g/L) 1
• Pregnant women (2nd/3rd trimester): Hb <11 g/dL (110 g/L) 1

Ferritin Thresholds (Most Important Single Test)

• <15 ng/mL (μg/L): Highly specific for iron deficiency (99% specificity), confirms absent iron stores 1
• <30 ng/mL: Generally indicates low body iron stores 1, 2
• <45 ng/mL: Optimal cutoff balancing sensitivity and specificity in clinical practice (92% specificity), particularly useful when inflammation is present 1
• >150 ng/mL: Makes absolute iron deficiency unlikely even with inflammation 1

Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated in chronic kidney disease, inflammatory conditions, infection, or malignancy. 1

Supporting Laboratory Markers

• Transferrin saturation <20%: Confirms iron deficiency, especially useful when ferritin is equivocal 1, 2
• Mean cell volume (MCV): Typically reduced (microcytosis), but may be normal with concurrent B12/folate deficiency 1
• Mean cell hemoglobin (MCH): More reliable than MCV, less machine-dependent, reduced in both absolute and functional iron deficiency 1

Functional Diagnostic Test

A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even when iron studies are equivocal. 1

Risk-Stratified Approach by Demographics

Premenopausal Women

• Most common cause: Menstrual blood loss (38% have iron deficiency without anemia, 13% have iron deficiency anemia) 2
• Investigation threshold: Age >45 years warrants full GI evaluation regardless of menstrual history 1
• Age <45 years: Only investigate with upper endoscopy if GI symptoms present; screen for celiac disease serologically 1
• Menorrhagia context: Over 50% have depleted iron stores, but only 25% are actually anemic 1

Pregnant Women

• Screening: Check hemoglobin at first prenatal visit 1
• Prevalence: Up to 84% have iron deficiency in third trimester in high-income countries 2
• Prevention: Start 30 mg/day oral iron supplementation at first prenatal visit 1

Men and Postmenopausal Women

• Most common cause: GI blood loss (including occult malignancy) 1
• Investigation mandate: Bidirectional endoscopy (gastroscopy and colonoscopy) strongly recommended to exclude GI malignancy 1
• Urgency markers: Hb <12 g/dL in men or <10 g/dL in postmenopausal women suggests more serious disease requiring urgent investigation 1

Essential Initial Workup

Mandatory Screening Tests

1. Celiac disease serology (tissue transglutaminase antibody): Found in 3-5% of IDA cases 1
2. Urinalysis/urine microscopy: Exclude urinary tract bleeding 1
3. H. pylori testing (non-invasive): Before endoscopy in asymptomatic patients 1

When to Perform Endoscopy

• Strong recommendation: Men and postmenopausal women with confirmed IDA should undergo gastroscopy with small bowel biopsy AND colonoscopy 1
• Conditional recommendation: Premenopausal women—consider based on age, symptoms, and risk factors 1
• Biopsy strategy: Reserve routine duodenal biopsies for positive celiac serology or high clinical suspicion; negative serology reduces post-test probability to 0.3% 1

Non-Anemic Iron Deficiency

Depleted iron stores (low ferritin) with normal hemoglobin does not typically warrant GI investigation in premenopausal women without other risk factors, as malignancy risk is very low. 1

However, investigate non-anemic iron deficiency in:

• Men of any age 1
• Postmenopausal women 1
• Anyone with GI symptoms 1
• Family history of GI malignancy 1

Key Clinical Pitfalls

• Do not rely on MCV alone: Microcytosis may be absent with concurrent folate/B12 deficiency or in early iron deficiency 1
• Avoid faecal occult blood testing: Insensitive and non-specific, not recommended 1
• Consider thalassemia: In microcytosis with normal iron studies, especially in appropriate ethnic backgrounds, check hemoglobin electrophoresis before GI investigation 1
• Dual pathology exists: 1-10% have bleeding sources in both upper and lower GI tracts, more common with increasing age 1
• NSAID use: Common cause of GI blood loss and iron deficiency; document and discontinue if possible 1