What is the diagnosis and recommended management for a patient with low serum iron, low total iron‑binding capacity, and high ferritin?

Diagnosis: Anemia of Chronic Disease (Inflammatory Anemia)

The combination of low serum iron, low TIBC, and high ferritin is diagnostic of anemia of chronic disease (ACD), not iron deficiency. This pattern indicates that iron is sequestered in storage sites (elevated ferritin) but unavailable for red blood cell production due to inflammatory cytokine-mediated hepcidin upregulation, which blocks iron release from macrophages. 1

Understanding the Laboratory Pattern

The key distinguishing features are:

• Low serum iron reflects reduced circulating iron available for erythropoiesis 2
• Low TIBC (total iron-binding capacity) is the hallmark that differentiates ACD from true iron deficiency—in iron deficiency, TIBC rises as the body attempts to capture more iron, whereas in ACD, inflammation suppresses transferrin production 3, 4
• High ferritin (>100 μg/L) confirms adequate or increased iron stores and excludes absolute iron deficiency 1, 4
• Calculate transferrin saturation (TSAT): If TSAT <20% with ferritin >100 μg/L, this confirms functional iron deficiency within the context of chronic disease 1

Immediate Diagnostic Workup

Step 1: Confirm Inflammation

• Measure CRP and ESR immediately—elevated values confirm an inflammatory process driving the anemia 1
• Check complete blood count with MCV and reticulocyte count to assess anemia severity and bone marrow response 1

Step 2: Identify the Underlying Chronic Disease

Search systematically for:

• Chronic infections: HIV, tuberculosis, endocarditis, osteomyelitis 2, 5
• Inflammatory conditions: Rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus 1
• Malignancy: Occult solid tumors, lymphoma, multiple myeloma 2, 5
• Chronic kidney disease: Check serum creatinine and eGFR (present in 16-31% of ACD cases) 6, 5
• Heart failure: A common but under-recognized cause 1

Step 3: Rule Out Coexistent True Iron Deficiency

• If ferritin is 30-100 μg/L in the presence of inflammation, a mixed picture of true iron deficiency plus ACD is likely 1
• Consider checking soluble transferrin receptor (sTfR) if ferritin and TSAT are discordant—elevated sTfR confirms real iron deficiency even when inflammation is present 1

Management Algorithm

Primary Strategy: Treat the Underlying Disease

The anemia of chronic disease resolves only when the underlying inflammatory, infectious, or neoplastic disorder is successfully treated. 2, 4 Iron supplementation alone will not correct ACD because the problem is iron sequestration, not depletion.

When to Consider Iron Supplementation

Iron therapy is indicated only if:

• Ferritin is 30-100 μg/L (mixed iron deficiency + ACD) 1
• **TSAT <20%** despite ferritin >100 μg/L (functional iron deficiency) 1
• Patient has inflammatory bowel disease: Use intravenous iron (ferric carboxymaltose 15 mg/kg, max 1000 mg per dose) because inflammation blocks oral iron absorption 1

When to Consider Erythropoiesis-Stimulating Agents (ESAs)

• Chronic kidney disease with hemoglobin <10 g/dL: ESAs can overcome the relative erythropoietin deficiency caused by inflammatory cytokines 2, 6
• Maintain ferritin >200 ng/mL and TSAT >20% when using ESAs to optimize response 6

Critical Pitfalls to Avoid

• Do not give oral iron empirically when ferritin is >100 μg/L—this will not improve anemia and may cause iron overload 1, 4
• Do not assume normal ferritin excludes iron deficiency in inflammatory states—ferritin up to 100 μg/L can still represent depleted stores when inflammation is present 1
• Do not overlook occult malignancy—24-40% of ACD cases have underlying diseases not traditionally associated with chronic inflammation 5
• Do not miss chronic kidney disease—check creatinine in all ACD patients, as renal insufficiency is present in 16-31% of cases and requires specific management 6, 5

Expected Clinical Course

• MCV is typically normal (normocytic) in pure ACD but may become low (microcytic) when true iron deficiency coexists 1
• Reticulocyte count is low or inappropriately normal for the degree of anemia, reflecting impaired bone marrow response to inflammatory cytokines 1
• Anemia severity in ACD is often underestimated—mean hematocrit can be as low as 31%, with 20% of patients having hematocrit <25% 5
• Red cell lifespan is mildly shortened due to inflammatory cytokine effects 2