What is the diagnosis and treatment for a patient with low iron (16), high Total Iron Binding Capacity (TIBC) (335), low percent saturation (5), and low ferritin (23)?

Diagnosis: Absolute Iron Deficiency Anemia

This patient has absolute iron deficiency anemia requiring oral iron supplementation and mandatory gastrointestinal evaluation to exclude malignancy as the source of blood loss. 1

Laboratory Interpretation

The iron panel definitively confirms absolute iron deficiency:

• Transferrin saturation of 5% is well below the 12% threshold that confirms absolute iron deficiency, indicating insufficient iron available for erythropoiesis 1
• Ferritin of 23 mcg/L indicates depleted iron stores, as levels <30 mcg/L generally confirm iron depletion 1
• TIBC of 335 mg/dL is elevated (normal range approximately 240-450), which is the expected compensatory response to iron deficiency as the body attempts to maximize iron binding capacity 2
• Serum iron of 16 mcg/dL is low, consistent with depleted iron stores 3

These findings represent the classic pattern of absolute iron deficiency: low iron, low ferritin, low transferrin saturation, and elevated TIBC. 4, 5

Required Additional Testing

Before initiating treatment, complete the following workup:

• Complete blood count with indices to assess for microcytic, hypochromic anemia and quantify severity 1
• Inflammatory markers (CRP or ESR) to exclude concurrent inflammation that could affect ferritin interpretation, though the low ferritin of 23 makes this less likely 1
• Hemoglobin electrophoresis if microcytosis is present with these iron studies to exclude thalassemia trait 1
• Stool guaiac testing for occult blood 1

Mandatory Investigation for Blood Loss

All adults with confirmed iron deficiency anemia require investigation for gastrointestinal blood loss, with the sole exception being premenopausal women with documented menorrhagia. 1

Critical Pitfall to Avoid

Do not assume menstruation is the cause in women over 40 years or those with severe anemia without excluding gastrointestinal pathology. 1

Gastrointestinal Evaluation Required:

• Bidirectional endoscopy (gastroscopy and colonoscopy) is mandatory to exclude gastrointestinal malignancy 1, 4
• Serological testing for celiac disease should be performed before endoscopy 4
• If both endoscopies are normal and anemia is severe, progressive, or unresponsive to iron therapy, investigate the small bowel with capsule endoscopy followed by enteroscopy 1, 4

Treatment Protocol

First-Line: Oral Iron Therapy

Initiate oral iron supplementation with ferrous preparations at 3-6 mg/kg of elemental iron per day (typically 150-200 mg elemental iron daily in adults). 6, 5

• Ferrous sulfate, ferrous gluconate, or ferrous fumarate are appropriate first-line options 2, 3
• Consider alternate-day dosing rather than daily dosing, as daily oral iron increases hepcidin levels that inhibit iron absorption 2
• Avoid taking iron with proton pump inhibitors, H2-blockers, or food that can precipitate iron and reduce absorption 2
• Common side effects include dyspepsia, constipation, and heartburn, which contribute to non-compliance 2

When to Consider Intravenous Iron

If the patient fails to respond to oral iron after 4-6 weeks (hemoglobin increase <1 g/dL), consider IV iron therapy: 2

• 65% of oral iron non-responders respond to IV iron compared to only 21% who respond to continued oral therapy 2
• Non-response may indicate malabsorption, non-compliance, ongoing blood loss exceeding absorption, or inflammation with hepcidin upregulation 2

Available IV iron preparations include: 2

• Low molecular weight iron dextran (requires test dose due to anaphylaxis risk)
• Iron sucrose (maximum 200 mg per dose, no test dose required)
• Ferric carboxymaltose
• Ferumoxytol
• Iron gluconate

Monitoring Response

• Recheck hemoglobin and iron indices after 4-6 weeks of therapy 5
• Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores 5, 3
• Target ferritin >30 mcg/L and transferrin saturation >20% 2

Additional Considerations

• Assess renal function (serum creatinine and GFR) to evaluate for chronic kidney disease as a contributing factor 2
• Check thyroid function as hypothyroidism can contribute to anemia 2
• Avoid blood transfusions unless absolutely necessary for hemodynamic instability, as oral or IV iron is safer and effective 1