What is the likely cause and appropriate work‑up for a female patient with hemoglobin 8.6 g/dL, platelet count 120 ×10⁹/L, normal serum iron and transferrin saturation, but low unsaturated iron‑binding capacity (UIBC) and low total iron‑binding capacity (TIBC)?

Anemia of Chronic Disease with Possible Concurrent Iron Deficiency

This patient's laboratory pattern—normal serum iron and transferrin saturation but low TIBC and low UIBC—strongly suggests anemia of chronic disease (ACD), not simple iron deficiency. The thrombocytopenia (platelets 120 ×10⁹/L) and significant anemia (hemoglobin 8.6 g/dL) raise concern for an underlying inflammatory, infectious, malignant, or bone marrow disorder. 1

Understanding the Iron Panel Pattern

• Low TIBC with normal serum iron indicates suppressed transferrin production, which occurs in chronic inflammation, liver disease, malignancy, or chronic infection—not in uncomplicated iron deficiency. 1, 2
• In true iron deficiency, TIBC is characteristically elevated (often >400 mg/dL) as the body attempts to maximize iron-binding capacity. 1, 3, 4
• TIBC equals serum iron plus UIBC; when both TIBC and UIBC are low but serum iron remains normal, transferrin synthesis is impaired rather than iron stores being depleted. 3
• Inflammation drives hepcidin upregulation, which sequesters iron in macrophages and hepatocytes, reducing both TIBC and iron availability for erythropoiesis despite adequate or even elevated total body iron stores. 1

Critical Next Steps in Workup

Mandatory Laboratory Tests

• Serum ferritin is essential: in the absence of inflammation, ferritin <30 μg/L confirms iron deficiency; however, ferritin is an acute-phase reactant and can be falsely elevated (up to 100–300 μg/L) in inflammatory states, masking true deficiency. 1, 3
• C-reactive protein (CRP) must be measured to identify concurrent inflammation, which profoundly affects ferritin interpretation and confirms anemia of chronic disease. 1, 3
• Complete blood count with differential and peripheral smear to evaluate red cell morphology (microcytosis, hypochromia, anisocytosis), white blood cell abnormalities, and platelet morphology—thrombocytopenia alongside anemia suggests bone marrow pathology or systemic disease. 3
• Reticulocyte count to assess bone marrow response: an inappropriately low reticulocyte count in the setting of anemia indicates impaired erythropoiesis. 1

Assess for Underlying Chronic Disease

• Renal function (serum creatinine, estimated glomerular filtration rate): chronic kidney disease (GFR <30 mL/min/1.73 m²) causes anemia through erythropoietin deficiency and contributes to functional iron deficiency. 1, 3
• Liver function tests: chronic liver disease reduces transferrin synthesis, lowering TIBC, and may cause cytopenias through hypersplenism. 1
• Thyroid function tests (TSH, free T4): hypothyroidism contributes to anemia and should be evaluated in all patients with unexplained anemia and chronic heart failure or other systemic conditions. 1
• Screening for malignancy and chronic infection: given the combination of anemia, thrombocytopenia, and suppressed TIBC, consider age-appropriate cancer screening, chest imaging, and infectious workup (HIV, hepatitis serologies, tuberculosis screening if risk factors present). 1

Gastrointestinal Evaluation

• Stool guaiac testing for occult blood: even in anemia of chronic disease, concurrent gastrointestinal blood loss is common and treatable. 3
• Upper and lower endoscopy if stool guaiac is positive or if the patient is postmenopausal (age not specified but implied by context), as gastrointestinal malignancy must be excluded. 3
• Celiac disease serologic screening (tissue transglutaminase IgA, total IgA): celiac disease has a 3–5% prevalence among patients with iron-deficiency anemia and can coexist with ACD. 3

Distinguishing Iron Deficiency from Anemia of Chronic Disease

Parameter	Iron Deficiency	Anemia of Chronic Disease	Mixed Picture
Serum Iron	↓	↓ or normal	↓
TIBC	↑↑ (>400 mg/dL)	↓ (<250 mg/dL)	Normal or ↓
Transferrin Saturation	↓↓ (<16%)	Normal or ↓	↓
Ferritin	↓ (<30 μg/L)	Normal or ↑ (>100 μg/L)	30–100 μg/L
CRP	Normal	↑	↑

1, 3

Common Diagnostic Pitfalls

• Do not rely on serum iron or transferrin saturation alone: these markers exhibit high day-to-day variability (influenced by meals, diurnal variation, inflammation) and have poor diagnostic accuracy for iron deficiency. 3, 5
• Normal serum iron does not exclude iron deficiency: early iron deficiency can present with elevated TIBC before serum iron falls, representing a compensatory mechanism to mobilize tissue iron. 4
• Ferritin thresholds must be adjusted for inflammation: in the presence of elevated CRP, ferritin up to 100 μg/L may still indicate iron deficiency; in chronic kidney disease or heart failure, ferritin <300 μg/L with transferrin saturation <20% defines functional iron deficiency. 1, 3
• Thrombocytopenia alongside anemia mandates bone marrow evaluation if no clear cause is identified: consider myelodysplastic syndrome, aplastic anemia, or bone marrow infiltration (lymphoma, leukemia, metastatic carcinoma). 3

Treatment Considerations

• Treat the underlying chronic disease first: managing inflammation, infection, malignancy, or organ dysfunction is essential for durable correction of anemia. 1, 3
• Oral iron is ineffective in anemia of chronic disease due to hepcidin-mediated blockade of intestinal absorption; if iron deficiency is confirmed (ferritin <100 μg/L, transferrin saturation <20%), intravenous iron is preferred. 1, 3
• Intravenous iron indications: gastrointestinal intolerance to oral iron, chronic kidney disease with GFR <30 mL/min/1.73 m², or lack of hematologic response after 4–8 weeks of adequate oral therapy. 3
• Target ferritin ≥100 μg/L and transferrin saturation ≥20% after iron repletion to ensure adequate iron stores and availability for erythropoiesis. 3