What is the diagnosis and treatment for a patient with elevated Total Iron Binding Capacity (TIBC) and low ferritin levels?

Diagnosis: Iron Deficiency Anemia

This patient has iron deficiency anemia, confirmed by the elevated TIBC of 376 mg/dL (normal range 240-450 mg/dL, though values >450 mg/dL are more definitively elevated) combined with low ferritin levels. 1

Understanding the Laboratory Findings

• Elevated TIBC indicates the body is attempting to compensate for low iron stores by producing more transferrin to capture available iron. 1
• When TIBC is elevated and ferritin is low (<30 ng/mL in patients without inflammation, or <45 ng/mL in anemic patients), this confirms absolute iron deficiency. 1
• The transferrin saturation (calculated as serum iron/TIBC × 100) is likely very low in this patient, which further confirms iron deficiency. 1
• A transferrin saturation <16% in adults is used to confirm iron deficiency, though in chronic kidney disease patients, <20% is the threshold. 2

Identifying the Underlying Cause

The priority is determining the source of iron loss, as iron deficiency in adults is blood loss until proven otherwise:

• For postmenopausal women and all men: Bidirectional endoscopy (both upper and lower) is strongly recommended to evaluate for gastrointestinal bleeding or malignancy. 1
• For premenopausal women: Bidirectional endoscopy is conditionally recommended unless menstrual losses clearly explain the deficiency. 1
• Before proceeding to endoscopy, obtain celiac disease serologic testing and non-invasive H. pylori testing. 1
• Check stool for occult blood to screen for gastrointestinal bleeding. 2

Common pitfall: In patients over 50 years old, 9% with iron deficiency anemia have gastrointestinal cancer, making endoscopic evaluation critical. 3

Treatment Protocol

First-Line: Oral Iron Supplementation

Begin with oral ferrous sulfate 325 mg daily or on alternate days (alternate-day dosing may improve tolerability). 1

• Expect hemoglobin to increase by 1-2 g/dL within one month if treatment is effective. 1, 3
• After 8-10 weeks of treatment, hemoglobin should normalize and ferritin should rise above 30 ng/mL. 1
• If hemoglobin does not increase by 1-2 g/dL within one month, consider malabsorption of oral iron, continued bleeding, or an unidentified lesion. 3

When to Use Intravenous Iron

Intravenous iron is indicated when: 1

• Intolerance to oral iron (gastrointestinal side effects are common and reduce adherence) 4
• Malabsorption conditions (celiac disease, inflammatory bowel disease, gastric bypass) 1, 4
• Ongoing significant blood loss 1
• Chronic inflammatory conditions (where oral absorption is impaired by elevated hepcidin) 1
• Pregnancy 1
• Need for rapid iron repletion 1

Newer intravenous iron formulations are safe with serious adverse events occurring very infrequently, though caution is needed regarding potential allergic reactions, hypophosphatemia, and iron overload. 5, 4

Monitoring and Follow-Up

• Recheck hemoglobin at one month to confirm 1-2 g/dL increase. 1, 3
• After 8-10 weeks, verify hemoglobin normalization and ferritin >30 ng/mL. 1
• If ferritin remains low despite treatment, consider intermittent oral supplementation and monitor every 6-12 months. 1

Special Consideration: Chronic Inflammatory Conditions

Important caveat: If the patient has chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease), ferritin can be falsely elevated as an acute-phase reactant. 2, 1

• In these patients, use transferrin saturation <20% to confirm iron deficiency even when ferritin appears normal or elevated. 2, 1
• For chronic kidney disease patients specifically, absolute iron deficiency is defined as transferrin saturation ≤20% and ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis). 6