In a patient with an iron saturation of 14%, low total iron‑binding capacity, and ferritin of 112 ng/mL, what is the likely cause of anemia and how should it be evaluated and managed?

Anemia of Chronic Disease (Functional Iron Deficiency)

This patient most likely has anemia of chronic disease (ACD), also called functional iron deficiency, characterized by low iron saturation (14%, normal >20%) with normal-to-elevated ferritin (112 ng/mL) and low TIBC—indicating iron is trapped in storage but not available for erythropoiesis due to inflammation.

Understanding the Iron Pattern

The combination of:

• Iron saturation 14% (low, <20%)
• Ferritin 112 ng/mL (normal/elevated, not depleted)
• Low TIBC (indicates inflammation, not true iron deficiency)

This pattern is pathognomonic for ACD/functional iron deficiency 1. In true iron deficiency anemia, you would see low ferritin (<30-45 ng/mL) with elevated TIBC as the body tries to capture more iron. The low TIBC here tells you this is an inflammatory process sequestering iron in macrophages 1.

Immediate Evaluation Steps

Search for the underlying inflammatory/chronic condition:

• Chronic kidney disease (check GFR—anemia common when <60 mL/min/1.73m²) 2
• Chronic heart failure (40-70% have functional iron deficiency) 2
• Inflammatory bowel disease (33% have iron deficiency with active disease) 2
• Malignancy (18-82% affected) 3
• Chronic infections
• Autoimmune conditions

Key lab work:

• Complete metabolic panel with creatinine/GFR
• CRP or ESR to confirm inflammation
• Review CBC for other cytopenias suggesting systemic disease

Critical Distinction: When to Suspect Coexisting True Iron Deficiency

Even with inflammation present, true iron deficiency can coexist if ferritin is <100 ng/mL 2. At ferritin 112 ng/mL, this patient is just above this threshold, making pure functional iron deficiency most likely. However, if ferritin were 45-100 ng/mL with transferrin saturation <20%, you would need to consider both diagnoses 4, 2.

Management Algorithm

1. Treat the Underlying Condition First

The anemia of chronic disease resolves when the inflammatory condition is corrected 1. This is your primary target.

2. Iron Replacement Strategy

For functional iron deficiency in specific conditions:

• Chronic heart failure with iron deficiency (ferritin <100 ng/mL OR ferritin 100-299 ng/mL with TSAT <20%): Use intravenous iron—this has proven prognostic benefit and improves exercise capacity 2, 3. Do NOT use oral iron in heart failure (poorly absorbed due to gut edema, no proven benefit) 2.

• Chronic kidney disease (GFR <30 mL/min/1.73m²): Coordinate with nephrology. Intravenous iron is typically required, especially if on dialysis 2. Functional iron deficiency in CKD is defined as TSAT ≤20% with ferritin ≤200 μg/L (hemodialysis) or ≤100 μg/L (predialysis/peritoneal dialysis) 2.

• Inflammatory bowel disease: Intravenous iron is preferred if oral iron is not tolerated or if there is moderate-to-severe anemia 2.

• Other inflammatory conditions without specific indications: Oral iron may be attempted, but absorption is impaired by elevated hepcidin from inflammation 2, 1. Consider intravenous iron if oral fails.

3. Gastrointestinal Evaluation

Even with suspected ACD, consider GI blood loss as a contributing factor, particularly in:

• Men and postmenopausal women (bidirectional endoscopy recommended) 4, 5, 3
• Patients on NSAIDs or anticoagulants 2
• Anyone with GI symptoms

Test for Helicobacter pylori and celiac disease noninvasively—both commonly cause iron deficiency 4, 5, 3.

Common Pitfalls to Avoid

1. Don't give oral iron to heart failure patients—it doesn't work and causes side effects 2.

2. Don't assume ferritin >100 ng/mL rules out iron deficiency in inflammation—use transferrin saturation <20% as your guide 2.

3. Don't treat with iron alone without identifying the underlying inflammatory condition—the anemia won't fully resolve 1.

4. Don't use TIBC to calculate iron needs—low TIBC indicates inflammation, not iron deficiency severity 1.

Monitoring Response

• Recheck hemoglobin in 2-4 weeks if using oral iron 5
• If no response to oral iron or intolerance develops, switch to intravenous iron 4, 5
• Continue monitoring the underlying inflammatory condition

The key to this patient's management is identifying and treating the chronic inflammatory or systemic disease driving the functional iron deficiency, while using intravenous iron if they have heart failure or CKD, or oral iron with close monitoring in other conditions.