Interpreting Iron Studies and Managing Suspected Iron Deficiency Anemia

Diagnostic Criteria

Iron deficiency anemia is confirmed when hemoglobin is <13 g/dL in men or <12 g/dL in non-pregnant women AND ferritin is <45 ng/mL. 1

Serum ferritin is the single most powerful test for iron deficiency 1
- Ferritin <15 μg/L is diagnostic of absent iron stores 1
- Ferritin <30 μg/L generally indicates low body iron stores 1
- Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated in chronic inflammation, malignancy, chronic kidney disease, or hepatic disease 1
- If ferritin is >100 μg/L, iron deficiency is almost certainly not present 1
Transferrin saturation <30% supports the diagnosis when ferritin is equivocal 1
Red cell indices (MCV, MCH) provide sensitive indicators of iron deficiency in the absence of chronic disease or hemoglobinopathy 1
- Mean cell hemoglobin (MCH) may be more reliable than MCV as it's less dependent on the counting machine used 1
Functional confirmation: A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even if iron studies are equivocal 1

All patients with confirmed IDA must be screened for celiac disease using tissue transglutaminase (tTG) antibody 1
Perform non-invasive testing for H. pylori 1

Men and postmenopausal women:

Strong recommendation for bidirectional endoscopy (upper and lower GI evaluation) regardless of symptoms 1
Upper GI endoscopy reveals a cause in 30-50% of patients 1
Dual pathology occurs in 10-15% of patients, so lower GI investigation is mandatory even if upper GI source is found, unless advanced gastric cancer or celiac disease is discovered 1

Premenopausal women:

All should be screened for celiac disease 1
Conditional recommendation for endoscopy - younger premenopausal women may reasonably choose initial empiric iron supplementation alone if they prioritize avoiding endoscopy risks over detecting rare neoplasia 1
Consider endoscopy based on age >50, marked anemia, significant family history of colorectal carcinoma, or failure to respond to iron therapy 1

Avoid routine biopsies for celiac disease and H. pylori 1
Reserve celiac biopsies for positive serologies requiring confirmation or endoscopic abnormalities 1
Small bowel biopsies should be taken during endoscopy as 2-3% of IDA patients have celiac disease 1
If bidirectional endoscopy is unrevealing in patients requiring antiplatelet/anticoagulant therapy, consider video capsule endoscopy for small bowel evaluation 1

Oral iron (first-line):

All patients should receive iron supplementation to correct anemia and replenish body stores 1
Continue until ferritin >100 ng/mL to ensure iron stores are restored 1
Iron therapy should continue for 6 months after hemoglobin normalizes to replace total iron stores 2

Parenteral iron (when oral fails):

Use when oral iron is not tolerated, there is malabsorption, or large ongoing blood losses 1, 3
Options include iron dextran, iron gluconate, or iron sucrose 3
In hemodialysis patients, iron sucrose 100 mg three times weekly for three weeks significantly increases serum iron and ferritin 4

If anemia does not resolve with iron supplementation, further direct visualization of the small bowel is indicated 1
In patients with recurrent IDA and normal bidirectional endoscopy, eradicate H. pylori if present 1
Continue hemoglobin monitoring after resolution 1

Never rely on hemoglobin/hematocrit alone - these decrease only with severe iron depletion and can miss early iron deficiency 5
Do not accept minor upper GI findings (esophagitis, erosions, aphthous ulceration, peptic ulcer) as the sole cause without completing lower GI investigation 1
Faecal occult blood testing has no benefit in IDA investigation 1
Do not skip celiac screening - it's found in 2-3% of IDA cases and changes management 1
In patients of appropriate ethnic background with microcytosis and normal iron studies, obtain hemoglobin electrophoresis to rule out thalassemia before extensive GI investigation 1