What is the management approach for an adult patient with no significant medical history presenting with iron deficiency anemia due to low transferrin saturation?

Management of Low Transferrin Saturation with Iron Deficiency Anemia

Start oral iron supplementation immediately with ferrous sulfate 324 mg daily (65 mg elemental iron) while simultaneously pursuing diagnostic workup to identify the underlying cause of blood loss or malabsorption. 1, 2

Confirming Iron Deficiency

Serum ferritin is the most powerful single test for diagnosing iron deficiency, with values <12-15 μg/L being diagnostic. 3 However, your patient's low transferrin saturation (<16-20%) confirms iron-deficient erythropoiesis and supports the diagnosis of absolute iron deficiency. 3, 1

• A transferrin saturation <16% in adults confirms iron deficiency with 93% specificity, though sensitivity is only 20%. 3
• Transferrin saturation <20% is diagnostic when combined with appropriate ferritin levels. 4, 5
• A good therapeutic response (hemoglobin rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even if iron studies are equivocal. 3, 1

Mandatory Investigation for Underlying Cause

Do not delay investigation pending response to iron therapy in adults without an obvious cause—this may miss gastrointestinal malignancy. 1

First-Line Investigations:

• Bidirectional endoscopy (gastroscopy and colonoscopy) is the first-line investigation for men and postmenopausal women with newly diagnosed iron deficiency anemia. 1
• Obtain small bowel biopsies during upper endoscopy, as 2-5% of iron deficiency anemia cases are due to celiac disease. 3, 1
• Perform stool guaiac testing for occult blood to evaluate for gastrointestinal bleeding. 1
• Test for Helicobacter pylori infection, as it is a common cause of iron deficiency anemia. 5

History Priorities:

• Document NSAID/aspirin use and stop if possible—these are common causes of occult GI blood loss. 3
• Assess dietary iron intake, particularly in vegetarians or restrictive eating patterns. 1
• In premenopausal women, evaluate menstrual history for heavy bleeding, though severe anemia still warrants full GI evaluation. 1
• Screen for malabsorption risk factors: prior gastrectomy, gastric bypass, inflammatory bowel disease, or symptoms suggesting celiac disease. 3, 4

Treatment Approach

Oral Iron (First-Line for Most Patients):

• Ferrous sulfate 324 mg daily (containing 65 mg elemental iron) is the recommended first-line therapy. 1, 2
• Alternative dosing: 100-200 mg elemental iron daily, or consider alternate-day dosing to improve absorption and reduce side effects. 1, 4, 5
• Reassess hemoglobin after 2-4 weeks; expect a rise of ≥10 g/L within 2 weeks if responding appropriately. 1, 5
• Approximately 50% of patients experience decreased adherence due to gastrointestinal side effects. 5

Intravenous Iron (Specific Indications):

Switch to intravenous iron if any of the following apply: 1, 4

• Intolerance to oral iron (gastrointestinal side effects)
• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss that cannot be controlled
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
• Inadequate response to oral iron after 2-4 weeks
• Second or third trimester of pregnancy

Hypersensitivity reactions to newer intravenous iron formulations are rare (<1%). 5

Common Pitfalls to Avoid

• Do not assume dietary deficiency alone without excluding pathologic causes, especially in men and postmenopausal women. 1
• Do not rely on transferrin saturation alone for diagnosis—it has high day-to-day variation and is affected by diurnal changes, meals, and inflammation. 3
• Serum ferritin can be falsely elevated by chronic infection, inflammation, malignancy, or liver disease; if ferritin is >100 μg/L, iron deficiency is almost certainly not present. 3
• Dual pathology (lesions in both upper and lower GI tracts) occurs in approximately 10% of cases, so complete both upper and lower GI evaluation even if one reveals a lesion. 3
• In patients with chronic kidney disease, normal transferrin saturation with low serum iron can still indicate iron deficiency and anemia risk. 6

Follow-Up Strategy

• Recheck hemoglobin at 2-4 weeks to confirm response to oral iron. 1, 5
• If hemoglobin does not increase by 1-2 g/dL (10-20 g/L) within one month, consider malabsorption, continued bleeding, or switch to intravenous iron. 7
• Repeat iron studies after 60-90 days of oral supplementation to confirm correction of iron deficiency. 8
• Further investigation is needed if iron deficiency has not been corrected despite adequate supplementation. 8