What is the most likely diagnosis and appropriate work‑up for a patient with hemoglobin 8.6 g/dL, mean corpuscular volume 95 fL, serum iron 44 µg/dL, transferrin saturation 19 %, and ferritin 240 ng/mL?

Anemia of Chronic Disease/Inflammation with Possible Functional Iron Deficiency

This patient most likely has anemia of chronic disease (ACD) with functional iron deficiency, characterized by normocytic anemia (MCV 95 fL), low iron (44 µg/dL), low transferrin saturation (19%), but elevated ferritin (240 ng/mL) indicating inflammation or chronic disease rather than true iron depletion. 1

Diagnostic Interpretation

Iron Studies Analysis

• Ferritin 240 ng/mL is elevated and serves as an acute-phase reactant, suggesting underlying inflammation, chronic disease, or malignancy rather than iron deficiency (which would show ferritin <100 ng/mL) 1
• Transferrin saturation of 19% is low (<20%), indicating insufficient iron available for erythropoiesis despite adequate tissue stores 1, 2
• This discordant pattern (elevated ferritin with low transferrin saturation) is the hallmark of functional iron deficiency in chronic disease states, where iron is sequestered in reticuloendothelial stores and cannot be mobilized for red cell production 1, 2

Hemoglobin and MCV Pattern

• Hemoglobin 8.6 g/dL represents moderate anemia (WHO classification: moderate anemia is 8.0-10.9 g/dL in women) 1
• Normal MCV of 95 fL excludes classic iron deficiency anemia, which typically presents with microcytosis (MCV <80 fL), and also excludes megaloblastic anemia (MCV >100 fL) 1, 3
• The normocytic pattern with these iron parameters strongly suggests ACD 1

Essential Next Steps in Work-Up

Immediate Laboratory Testing

• Obtain reticulocyte count or reticulocyte index to assess bone marrow response and distinguish between hypoproliferative anemia (low reticulocyte count) versus hemolytic process (elevated reticulocyte count) 1, 3
• Order peripheral blood smear to evaluate for schistocytes (suggesting microangiopathic hemolysis), hypochromic cells, or other morphologic abnormalities 1, 3
• Measure inflammatory markers including C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) to confirm inflammation as the cause of elevated ferritin 1
• Check lactate dehydrogenase (LDH) and haptoglobin to exclude hemolysis as a contributing factor 3

Additional Diagnostic Considerations

• Evaluate for underlying chronic disease including chronic kidney disease (check creatinine and estimated GFR), malignancy, autoimmune conditions, or chronic infections that commonly cause ACD 1
• Consider gastrointestinal evaluation if there is any suspicion of occult blood loss, particularly in patients with risk factors for GI malignancy, despite the elevated ferritin 1
• Assess for combined deficiencies: Check vitamin B12 and folate levels, as combined deficiencies can mask microcytosis and present with normal MCV 1, 4

Management Algorithm

If Reticulocyte Count is Low (Hypoproliferative)

• Confirms anemia of chronic disease as the primary diagnosis 1
• Address underlying inflammatory condition as the primary therapeutic target rather than empiric iron supplementation 1, 2
• Iron supplementation is NOT indicated when ferritin >100 ng/mL unless there is documented ongoing blood loss 1
• Consider erythropoiesis-stimulating agents only if treating underlying chronic kidney disease or other specific conditions with established guidelines 1

If Reticulocyte Count is Elevated

• Investigate for hemolysis or acute blood loss with complete hemolysis panel (LDH, haptoglobin, indirect bilirubin, direct antiglobulin test) 3
• Examine peripheral smear carefully for schistocytes (>1% suggests thrombotic microangiopathy requiring urgent evaluation) 3
• If schistocytes present, immediately order ADAMTS13 activity level, complement levels (C3, C4, CH50), and consider hematology consultation for possible TTP/HUS 3

Critical Pitfalls to Avoid

• Do not interpret ferritin in isolation: Ferritin >100 ng/mL does NOT exclude functional iron deficiency in the setting of inflammation, but ferritin 240 ng/mL makes true iron depletion very unlikely 1, 2
• Do not empirically supplement iron based solely on low transferrin saturation when ferritin is elevated, as this can lead to iron overload without improving anemia 1, 2
• Do not miss combined pathology: The normal MCV could represent a mixed picture of iron deficiency plus B12/folate deficiency, or thalassemia trait with concurrent inflammation 1, 5
• Do not delay evaluation for malignancy or chronic disease: ACD pattern warrants investigation for underlying serious conditions including occult malignancy, particularly in older patients 1

Special Consideration for Chronic Kidney Disease

• If creatinine is elevated, this patient may have CKD-related anemia where ferritin targets are higher (goal ferritin >100 ng/mL, transferrin saturation >20% before considering iron therapy) 1
• In CKD patients, transferrin saturation <20% with ferritin 100-500 ng/mL may warrant iron supplementation to optimize erythropoiesis-stimulating agent response 1