What is the most likely diagnosis and recommended acute management for a patient with severe normocytic‑macrocytic anemia (hemoglobin 6.6 g/dL, hematocrit 21.3 %), low serum iron, low total iron‑binding capacity, markedly elevated ferritin, low reticulocyte response, neutrophilic leukocytosis (white‑blood‑cell count 20 ×10^3/µL, 92% neutrophils), and a mildly prolonged prothrombin time (15.8 seconds, activity 68%)?

Anemia of Chronic Inflammation with Functional Iron Deficiency

This patient has anemia of chronic inflammation (anemia of chronic disease) driven by an acute inflammatory or infectious process, evidenced by markedly elevated ferritin (970 µg/L), low TIBC (144 µg/dL), low serum iron (70 µg/dL), severe neutrophilic leukocytosis (WBC 20 × 10³/µL with 92% neutrophils), and a blunted reticulocyte response (2.2%) despite severe anemia (hemoglobin 6.6 g/dL). 1

Diagnostic Interpretation

Iron Studies Pattern

• The combination of elevated ferritin >100 µg/L, low TIBC, and low serum iron confirms anemia of chronic inflammation with functional iron deficiency—iron is sequestered in macrophages by hepcidin and cannot be mobilized for erythropoiesis. 1
• Transferrin saturation can be calculated as (serum iron ÷ TIBC) × 100 = (70 ÷ 144) × 100 ≈ 49%, which is elevated rather than low, further supporting iron sequestration rather than absolute iron deficiency. 1
• Ferritin >100 µg/L with low TIBC definitively excludes absolute iron deficiency and confirms anemia of chronic disease. 1

Reticulocyte Response

• A reticulocyte count of 2.2% translates to a reticulocyte index <1.0–2.0 when corrected for the degree of anemia (hematocrit 21.3%), confirming a hypoproliferative process rather than hemolysis or acute blood loss. 1
• The blunted marrow response despite severe anemia indicates inflammatory cytokine suppression of erythropoietin production and direct inhibition of erythroid progenitors. 1

Inflammatory Markers

• The profound neutrophilic leukocytosis (92.1% neutrophils, absolute count ≈18.4 × 10³/µL) with relative lymphopenia (3.3%) signals an acute bacterial infection, severe inflammation, or possible underlying malignancy. 1
• The mildly prolonged prothrombin time (15.8 seconds, 68% activity) may reflect consumptive coagulopathy, hepatic synthetic dysfunction from sepsis, or disseminated intravascular coagulation. 1

Immediate Diagnostic Workup

Inflammatory and Infectious Evaluation

• Measure C-reactive protein and erythrocyte sedimentation rate immediately to quantify the inflammatory burden; CRP normalizes more rapidly than ESR during treatment response. 1
• Obtain blood cultures (aerobic and anaerobic) before initiating antibiotics if sepsis is suspected, given the severe leukocytosis and anemia. 1
• Order chest radiograph, urinalysis with culture, and consider abdominal imaging (CT or ultrasound) to identify occult infection or abscess. 1

Malignancy Screening

• Markedly elevated ferritin (970 µg/L) combined with normocytic anemia raises suspicion for hematologic malignancies (multiple myeloma, lymphoma, myelodysplastic syndrome) or solid tumors; obtain peripheral blood smear, serum protein electrophoresis, and lactate dehydrogenase. 1
• Examine the peripheral smear for dysplastic red cells, blasts, rouleaux formation, or other abnormal morphology that would mandate bone marrow examination. 1

Renal Function Assessment

• Measure serum creatinine and estimate glomerular filtration rate; chronic kidney disease (GFR <30 mL/min/1.73 m²) produces a similar anemia pattern through erythropoietin deficiency. 1
• If creatinine is ≥2 mg/dL and no other cause is identified, anemia is likely due to erythropoietin deficiency. 1

Hepatic and Coagulation Evaluation

• Check liver function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin) to assess for hepatic dysfunction contributing to the prolonged prothrombin time. 1
• Measure fibrinogen, D-dimer, and peripheral smear for schistocytes to exclude disseminated intravascular coagulation. 1

Indications for Bone Marrow Examination

Bone marrow aspiration and biopsy are indicated if: 1

• Peripheral smear shows dysplastic features, blasts, or unexplained abnormalities
• Progressive anemia despite optimal treatment of the underlying inflammatory condition
• Clinical suspicion for myelodysplastic syndrome, especially with the blunted reticulocyte response
• Unexplained pancytopenia or abnormalities affecting multiple cell lines (note: platelets are preserved at 341 × 10³/µL, but severe lymphopenia is present)
• Failure to identify a cause after comprehensive non-invasive workup

Acute Management Priorities

Transfusion Threshold

• Transfuse packed red blood cells immediately if hemoglobin is <7–8 g/dL or the patient exhibits severe symptoms (chest pain, resting dyspnea, hemodynamic instability), regardless of the numeric hemoglobin value. 1
• At hemoglobin 6.6 g/dL, most patients will be symptomatic and require transfusion; use leukoreduced products to minimize febrile reactions. 1, 2

Treatment of Underlying Condition

• Primary management focuses on identifying and treating the underlying inflammatory, infectious, or malignant process—direct anemia therapy is secondary. 1
• If bacterial infection is confirmed, initiate appropriate antibiotics; if malignancy is identified, follow tumor-specific treatment guidelines. 1

Iron Supplementation Contraindication

• Do NOT administer oral or intravenous iron when ferritin is markedly elevated (970 µg/L); hepcidin-mediated sequestration prevents utilization and may cause iron overload. 1
• Iron therapy is appropriate only when ferritin falls below 100 µg/L after the inflammatory condition is controlled. 1

Erythropoiesis-Stimulating Agents

• Reserve erythropoiesis-stimulating agents (ESAs) for patients who remain symptomatic with hemoglobin <10 g/dL despite optimal control of the underlying condition. 1
• In chronic kidney disease, do not start ESAs until hemoglobin falls below 10 g/dL in asymptomatic patients; use the minimal dose to lessen transfusion needs rather than targeting a specific hemoglobin level. 1

Monitoring and Follow-Up

• Repeat complete blood count 4–6 weeks after initiating treatment of the underlying condition; serial reticulocyte measurements serve as a rapid indicator of therapeutic response. 1
• Monitor hemoglobin every 6 months for stable inflammatory disease and more frequently during active inflammation. 1
• Recheck iron studies only after the inflammatory markers normalize; ferritin will remain elevated until the underlying process is controlled. 1

Critical Pitfalls to Avoid

• Do not treat with iron supplementation based on low serum iron alone; the elevated ferritin and low TIBC confirm functional iron deficiency, not absolute deficiency. 1
• Do not delay investigation for infection or malignancy; the severity of leukocytosis and anemia demands urgent evaluation. 1
• Do not assume anemia of chronic disease without measuring inflammatory markers and excluding malignancy, especially with ferritin >900 µg/L. 1
• Do not target hemoglobin normalization with ESAs; this increases thrombotic risk and mortality without improving quality of life. 1