What is the diagnosis and treatment for a patient with high iron binding capacity, low ferritin, low total iron, and low saturation?

Diagnosis: Iron Deficiency Anemia

This laboratory pattern—high total iron-binding capacity (TIBC) with low ferritin, low serum iron, and low transferrin saturation—is diagnostic of absolute iron deficiency anemia (IDA), not anemia of chronic disease. 1, 2

Understanding the Laboratory Pattern

The key distinguishing feature is the elevated TIBC, which differentiates this from anemia of chronic disease:

• Iron deficiency anemia shows low iron, high TIBC (>350 μg/dL), and low transferrin saturation 1
• Anemia of chronic disease shows low iron, low TIBC (<250 μg/dL), and variable transferrin saturation 1, 3
• Low ferritin (<15 μg/L in most contexts, <30 μg/L in some guidelines) confirms depleted iron stores and rules out functional iron deficiency 4, 1

Identifying the Underlying Cause

Blood loss is the most common cause and must be investigated systematically:

In Adult Men and Postmenopausal Women:

• Gastrointestinal blood loss is the priority concern, as asymptomatic colonic and gastric carcinoma may present with IDA 4
• Men with Hb <12 g/dL and postmenopausal women with Hb <10 g/dL should be investigated more urgently, as lower hemoglobin suggests more serious disease 4
• Endoscopic evaluation is recommended, beginning with colonoscopy if the patient is older than 50 2
• Dual pathology (bleeding sources in both upper and lower GI tracts) occurs in 1-10% of patients, particularly in older individuals 4

In Premenopausal Women:

• Menstrual blood loss is the most common cause 4
• If review of symptoms, history, and physical examination are negative, a trial of oral iron is reasonable with hemoglobin rechecked at one month 2
• If hemoglobin does not increase by 1-2 g/dL in one month, consider malabsorption, continued bleeding, or occult lesion 2

Additional Causes to Evaluate:

• Screen for celiac disease with tissue transglutaminase (tTG) antibody testing at presentation 4
• NSAID use (common cause of GI blood loss) 4
• Poor dietary iron intake 4, 2
• Blood donation 4
• History of gastrectomy 4

Treatment Approach

Oral Iron Therapy (First-Line):

• Oral iron supplementation is the initial treatment for most patients with adequate doses 3, 5
• Monitor hemoglobin at one month; expect 1-2 g/dL increase if treatment is effective 2
• Stop NSAID use if present 4

When Oral Iron Fails or Is Inappropriate:

Intravenous iron should be considered when: 5, 6

• Large ongoing blood losses exceed oral iron absorption
• Iron malabsorption is present (e.g., celiac disease, inflammatory bowel disease)
• Intolerance to oral iron occurs
• Rapid iron replenishment is necessary

Monitoring Treatment Response:

• Inadequate response to oral iron indicates: 2, 3
  • Malabsorption of oral iron
  • Continued bleeding
  • Unidentified lesion
  • Concomitant folate or B12 deficiency
• If no response occurs, proceed with endoscopic evaluation rather than continuing ineffective oral therapy 2

Critical Pitfall to Avoid

Do not confuse this pattern with anemia of chronic disease. The elevated TIBC is the critical discriminator—it indicates the body is attempting to maximize iron transport capacity in response to depleted stores, which does not occur in inflammatory conditions where TIBC is suppressed 1, 3. Misdiagnosing this as anemia of chronic disease would delay investigation of potentially serious causes like gastrointestinal malignancy 4, 2.