What is the recommended management of iron‑deficiency anemia, including identification of cause, oral iron dosing, indications for intravenous iron, transfusion thresholds, dietary advice, monitoring, and follow‑up?

Management of Iron Deficiency Anemia

Oral Iron Replacement: First-Line Treatment

All patients with iron deficiency anemia should receive oral iron supplementation with ferrous sulfate 200 mg three times daily (65 mg elemental iron per dose) to correct anemia and replenish body stores. 1, 2

• Alternative formulations including ferrous gluconate and ferrous fumarate are equally effective if ferrous sulfate is not tolerated 1
• Liquid preparations may be better tolerated when tablets cause gastrointestinal side effects 1
• Adding ascorbic acid (vitamin C) enhances iron absorption and should be considered when response is poor 1, 2
• Continue iron supplementation for 3 months after hemoglobin normalizes to replenish body stores 1, 2
• Expected response: hemoglobin should rise by 2 g/dL after 3-4 weeks or ≥10 g/L within 2 weeks 1, 2

When Oral Iron Fails

Failure to respond to oral iron indicates one of four problems: 1, 2

• Poor compliance (most common)
• Misdiagnosis
• Continued blood loss
• Malabsorption

Intravenous Iron: Specific Indications

Parenteral iron should only be used when there is documented intolerance to at least two different oral iron preparations or confirmed non-compliance. 1

• IV iron is appropriate when oral iron cannot be tolerated, absorption is impaired, or rapid iron replenishment is necessary 3, 4
• Parenteral iron is painful (intramuscular), expensive, carries risk of anaphylactic reactions, and produces no faster hemoglobin rise than oral preparations 1
• Consider IV iron for transfusion-dependent IDA or when rapid hematologic response is required 3

Blood Transfusion: Reserve for Hemodynamic Instability

Blood transfusions should be reserved exclusively for patients with or at risk of cardiovascular instability due to the severity of their anemia. 1

• Judicious use is recommended; transfusion is indicated only for severe, symptomatic IDA with hemodynamic compromise 3
• Transfusion should not be routine treatment for stable patients regardless of hemoglobin level 1

Investigation of Underlying Cause: Critical for All Patients

Who Requires Full GI Investigation

All postmenopausal women and all men with confirmed IDA require both upper and lower GI investigations unless there is documented significant overt non-GI blood loss. 1

The investigation algorithm: 1, 2, 5

1. Upper endoscopy with small bowel biopsies (reveals cause in 30-50% of patients)

   • Small bowel biopsies are mandatory to screen for celiac disease, found in 2-5% of IDA cases 1, 2, 5

2. Lower GI investigation (colonoscopy preferred over barium enema)

   • Must be performed even if upper endoscopy reveals a lesion, because dual pathology occurs in 10-15% of patients 1
   • Only advanced gastric cancer or celiac disease should deter lower GI investigation 1

3. Screen all patients for celiac disease with serological testing and duodenal biopsies 1, 2, 5

4. Urinalysis to exclude urinary tract bleeding 2, 6

When to Investigate Further

Further small bowel visualization is not necessary unless IDA is transfusion-dependent or hemoglobin cannot be restored/maintained with iron therapy. 1

• Enteroscopy may be helpful in transfusion-dependent IDA to detect and treat small bowel angiodysplasia 1
• Small bowel radiology is rarely useful unless history suggests Crohn's disease 1
• Faecal occult blood testing is of no benefit in investigating IDA (insensitive and non-specific) 1

Special Population: Premenopausal Women

• All premenopausal women with IDA should be screened for celiac disease 1
• Women over age 45 should undergo full GI investigation according to standard guidelines 1
• For women under 45, base upper and lower GI investigations on clinical judgment, considering family history, severity of anemia, and presence of alarm symptoms 1

Critical Diagnostic Pitfall

Finding one cause should NOT stop further investigation—multiple causes coexist in 10-15% of patients. 1, 2, 5

• Do not accept minor findings (oesophagitis, erosions, aphthous ulceration, peptic ulcer) as the sole cause without completing lower GI investigation 1
• Dual pathology increases with patient age 1

Diagnostic Confirmation

Serum ferritin is the most powerful single test for iron deficiency. 1, 2, 5

• Red cell indices (MCV, MCH) provide sensitive indication of iron deficiency in the absence of chronic disease or hemoglobinopathy 1
• Ferritin may be falsely elevated in inflammatory conditions, chronic disease, or malignancy 2, 5
• The lower the hemoglobin, the more likely there is serious underlying pathology and the more urgent the need for investigation 1
• Hemoglobin electrophoresis is recommended when microcytosis and hypochromia are present in patients of appropriate ethnic background to prevent unnecessary GI investigation 1

Monitoring and Follow-Up Protocol

After achieving normal hemoglobin, monitor hemoglobin concentration and red cell indices every 3 months for 1 year, then recheck after an additional year. 1, 2

• Give additional oral iron if hemoglobin or MCV falls below normal (check ferritin in doubtful cases) 1
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with iron supplementation 1
• Iron deficiency does not return in most patients in whom a cause was not initially found after complete investigation 1

Addressing Underlying Causes

NSAID Use

• NSAIDs are common and frequently unreported causes of IDA 1, 2, 6
• Explicitly ask about all NSAID use, including over-the-counter medications that patients often don't consider worth mentioning 6
• Stop NSAIDs when identified as contributing factor 1

Helicobacter pylori

• In patients with recurrent IDA and normal repeat endoscopies, eradicate H. pylori if present 1

Dietary Deficiency

• Address dietary deficiency when identified, but do not assume this is the sole cause—complete GI investigation is still required 1, 6

Common Clinical Pitfalls to Avoid

• Never assume dietary deficiency is the sole cause even with positive dietary history; full investigation remains mandatory 6
• Do not stop at finding minor upper GI lesions without completing colonoscopy 1
• Do not use parenteral iron as first-line simply for convenience—oral iron must be tried first with at least two different formulations 1
• Do not transfuse stable patients regardless of hemoglobin number 1, 3
• Do not skip celiac screening in any patient with unexplained IDA 1, 2, 5, 6