What is the diagnosis and management for a patient with anemia, characterized by low hemoglobin (Hb), low hematocrit (Hct), low red blood cells (RBC), normal white blood cell count (WBC), elevated segmented neutrophils (seg), low lymphocytes, high monocytes, low mean corpuscular hemoglobin concentration (MCHC), high red cell distribution width (RDW), low mean platelet volume (MPV), normal reticulocyte count, and high ferritin levels?

Anemia of Chronic Disease/Inflammation

This patient has anemia of chronic disease (ACD), evidenced by the combination of normocytic anemia (normal MCHC suggests normocytic despite low MCHC value), elevated ferritin, normal reticulocyte count, and inflammatory markers (elevated segmented neutrophils, high monocytes). The high RDW suggests possible coexisting iron deficiency that is masked by inflammation. 1, 2

Diagnostic Interpretation

Key Laboratory Findings Point to ACD:

• Elevated ferritin with anemia is the hallmark finding—ferritin >100 μg/dL essentially excludes pure iron deficiency anemia, though concurrent functional iron deficiency remains possible in inflammatory states 1, 2
• Normal reticulocyte count indicates inadequate bone marrow response to anemia, characteristic of impaired erythropoiesis seen in chronic disease rather than hemolysis or acute blood loss 1, 3
• Elevated inflammatory markers (high segmented neutrophils and monocytes) directly support an underlying inflammatory or chronic disease process 3
• High RDW with low MCHC suggests a mixed picture where iron-restricted erythropoiesis coexists with inflammation—the elevated RDW indicates a heterogeneous red cell population that can occur when microcytosis and normocytosis overlap 1, 2

Critical Distinction from Iron Deficiency:

The elevated ferritin is decisive here. While ferritin can be falsely elevated in inflammation even with concurrent iron deficiency, levels >100 μg/dL make pure iron deficiency highly unlikely. 1 However, functional iron deficiency (inability to mobilize iron stores for erythropoiesis despite adequate stores) remains possible. 1

Immediate Next Steps

Essential Additional Testing:

• Transferrin saturation (TSAT): Calculate from serum iron and total iron-binding capacity (TIBC). TSAT <16-20% indicates functional iron deficiency despite elevated ferritin 1, 3
• C-reactive protein (CRP): Quantify the degree of inflammation to better interpret ferritin levels 3
• Comprehensive metabolic panel with creatinine: Rule out chronic kidney disease, a common cause of normocytic anemia with impaired erythropoietin production 1
• TSH: Exclude hypothyroidism as a contributing factor 2

Search for Underlying Chronic Disease:

• Gastrointestinal evaluation: Even with elevated ferritin, occult GI bleeding can coexist. Stool guaiac testing is indicated, and if positive, endoscopy should be pursued as 60-70% of patients with anemia referred for endoscopy have identifiable GI pathology 1, 4
• Medication review: NSAIDs are a common cause of occult GI blood loss and should be discontinued if possible 1
• Malignancy screening: Age-appropriate cancer screening is warranted given that malignancy commonly presents with ACD 1
• Rheumatologic evaluation: If no obvious source is found, consider autoimmune conditions that cause chronic inflammation 3

Management Algorithm

If TSAT <20% (Functional Iron Deficiency):

• Oral iron trial: 100-200 mg elemental iron daily for 3 weeks can be both diagnostic and therapeutic. Response (hemoglobin increase ≥2 g/dL within 4 weeks) confirms iron-restricted erythropoiesis 1, 2
• Parenteral iron: Consider if oral iron is not tolerated, not absorbed, or ineffective, particularly in inflammatory bowel disease or chronic kidney disease 1, 5

If TSAT ≥20% (Pure ACD):

• Treat underlying condition: The primary intervention is addressing the inflammatory or chronic disease process causing the anemia 1, 3
• Erythropoiesis-stimulating agents (ESAs): In chronic kidney disease with hemoglobin <10 g/dL, ESAs may be indicated per kidney disease guidelines 1
• Avoid unnecessary iron supplementation: Iron therapy without documented deficiency can lead to iron overload in ACD 1

Critical Pitfalls to Avoid

• Do not assume elevated ferritin excludes all iron deficiency: In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency. Always check TSAT to identify functional iron deficiency 1, 2
• Do not overlook mixed deficiency states: The high RDW is a red flag for coexisting iron deficiency masked by inflammation. Combined deficiencies require addressing both issues 1, 2
• Do not delay investigation for occult bleeding: Despite elevated ferritin, GI blood loss can coexist and requires evaluation, especially with NSAID use 1
• Do not treat empirically without identifying the underlying cause: ACD is a diagnosis of exclusion after ruling out treatable causes like iron deficiency, B12/folate deficiency, hypothyroidism, and chronic kidney disease 1, 3

When to Refer to Hematology:

If anemia persists despite treating identified deficiencies and underlying conditions, or if leucopenia/thrombocytopenia develops suggesting bone marrow pathology (myelodysplastic syndrome, malignancy), hematology referral with possible bone marrow biopsy is warranted. 2