What is the most likely diagnosis and recommended management for a patient with normal serum iron, elevated serum ferritin, low total iron‑binding capacity (TIBC), and a hemoglobin at the low end of normal?

Anemia of Chronic Disease (Inflammatory Anemia)

The most likely diagnosis is anemia of chronic disease (also called inflammatory anemia), characterized by iron sequestration in the reticuloendothelial system despite adequate total body iron stores. 1, 2

Diagnostic Interpretation

Your laboratory pattern—normal serum iron, elevated ferritin, low TIBC, and low-normal hemoglobin—is the classic signature of inflammatory iron block rather than true iron deficiency 1, 2:

• Elevated ferritin (>100 µg/L) combined with low TIBC indicates anemia of chronic disease, where inflammation drives hepcidin production that traps iron in macrophages and hepatocytes 1, 2
• Normal serum iron distinguishes this from absolute iron deficiency, where serum iron would be low 1, 2
• Low TIBC reflects the suppression of transferrin synthesis during inflammation, as transferrin is a negative acute-phase reactant 1, 2
• Low-normal hemoglobin results from both reduced erythropoietin production and functional iron deficiency—iron is present but unavailable for red blood cell production 1, 2

Immediate Diagnostic Steps

Calculate Transferrin Saturation

• Use the formula: (serum iron × 100) ÷ TIBC to determine iron availability for erythropoiesis 1, 2
• TSAT <20% confirms functional iron deficiency despite elevated ferritin, indicating that iron is sequestered and cannot be mobilized for red cell production 1, 2

Measure Inflammatory Markers

• Order CRP and ESR immediately to confirm the presence of inflammation 1, 2
• Elevated inflammatory markers validate the diagnosis of anemia of chronic disease and explain why ferritin is high despite inadequate iron delivery 1, 2

Obtain Complete Blood Count with Indices

• Check MCV, MCH, and RDW to characterize red cell morphology 2
• Anemia of chronic disease typically presents with normocytic anemia (normal MCV), though microcytosis can develop when true iron deficiency coexists 2
• Order reticulocyte count to assess marrow response; low or normal reticulocytes indicate inadequate production rather than hemolysis 2

Differential Diagnosis Algorithm

If Ferritin 30–100 µg/L with Elevated CRP/ESR

• This pattern indicates mixed iron deficiency (absolute + functional) coexisting with inflammation 1, 2
• TSAT <20% confirms that true iron deficiency is present alongside inflammatory iron block 1, 2
• Both iron supplementation and treatment of the underlying inflammatory condition are required 1, 2

If Ferritin >100 µg/L with Elevated CRP/ESR

• This defines pure anemia of chronic disease with functional iron deficiency 1, 2
• TSAT <20% demonstrates iron sequestration despite adequate stores 1, 2
• The primary intervention is aggressive management of the underlying inflammatory disease, not iron supplementation 1, 2

If Ferritin >100 µg/L with Normal CRP/ESR

• Absolute iron deficiency is essentially ruled out when ferritin >150 µg/L without inflammation 1, 2
• Investigate alternative causes of anemia: vitamin B12 or folate deficiency, hemolysis, bone marrow disease, chronic kidney disease, or hypothyroidism 2

Identifying the Underlying Inflammatory Condition

The most critical step is determining what chronic disease is driving the inflammatory response 1, 2:

• Chronic infections (e.g., tuberculosis, HIV, osteomyelitis, endocarditis) 1, 2
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1, 2
• Chronic kidney disease (reduced erythropoietin production compounds the anemia) 2
• Chronic heart failure (NYHA class II–IV) 2
• Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) 1, 2
• Occult malignancy (especially hematologic malignancies, gastrointestinal cancers) 1, 2
• Chronic liver disease (hepatitis, cirrhosis) 1, 2

Management Strategy

Primary Treatment: Address the Underlying Disease

• Controlling inflammation is the cornerstone of therapy; iron supplementation alone will not correct anemia of chronic disease 1, 2
• Successful treatment of the inflammatory condition permits mobilization of sequestered iron stores 1, 2

Iron Supplementation Decision

• Iron supplementation is NOT the primary intervention when ferritin >100 µg/L with TSAT <20% in the setting of active inflammation 1, 2
• If ferritin is 30–100 µg/L with TSAT <20% and elevated CRP, initiate oral iron therapy (ferrous sulfate 65 mg elemental iron daily or alternate-day dosing) while concurrently treating the inflammatory condition 1, 2
• After inflammation resolves, re-measure iron studies; if ferritin falls to 30–100 µg/L while TSAT remains <20%, true iron deficiency is present and iron supplementation should be started 1, 2

When to Consider Intravenous Iron

• In chronic kidney disease (non-dialysis, not receiving ESAs), consider IV iron if TSAT ≤30% and ferritin ≤500 ng/mL to achieve hemoglobin rise without initiating ESA therapy 2
• In chronic heart failure (NYHA class II–IV), IV iron (ferric carboxymaltose or iron sucrose) improves functional capacity and quality of life when ferritin <100 ng/mL or ferritin 100–300 ng/mL with TSAT <20% 2
• In inflammatory bowel disease with active inflammation, oral iron is poorly absorbed; IV iron is preferred 1, 2

Erythropoiesis-Stimulating Agents (ESAs)

• Initiate ESA therapy only after iron deficiency has been corrected and other reversible causes (vitamin B12/folate deficiency, blood loss, inflammation, malignancy) have been excluded 2
• Weigh the potential benefits of reducing transfusion requirements against risks such as anaphylactoid reactions and uncertain long-term safety 2

Follow-Up and Monitoring

• Repeat CBC, iron studies, and inflammatory markers (CRP, ESR) after treating the underlying inflammatory condition 1, 2
• If hemoglobin fails to improve despite controlling inflammation, re-evaluate for coexisting vitamin B12 or folate deficiency, ongoing blood loss, or primary bone marrow disease 2
• Target ferritin >100 ng/mL to restore iron stores once inflammation resolves 1

Critical Pitfalls to Avoid

• Do not interpret elevated ferritin (>100 µg/L) during active inflammation as evidence of adequate iron stores; it reflects the acute-phase response, not true iron sufficiency 1, 2
• Do not start empiric iron supplementation solely based on low hemoglobin when ferritin is elevated and inflammation is active; iron will not be utilized until inflammation subsides 1, 2
• Do not rely on ferritin alone in the presence of inflammation; always calculate TSAT to assess functional iron availability 1, 2
• Do not overlook occult malignancy; chronic inflammation with anemia may be the presenting sign of gastrointestinal or hematologic cancer 1, 2
• Do not assume the anemia will self-correct; monitor hemoglobin response after treating the inflammatory condition, as underlying iron deficiency may become apparent once inflammation resolves 1, 2