How should I manage a patient with mild‑to‑moderate normocytic anemia (hemoglobin 9.8 g/dL, MCV 82 fL), low reticulocyte count, low serum iron, high ferritin, elevated vitamin B12, normal folate, and no current supplementation?

Management of Normocytic Anemia with Low Reticulocyte Count and Elevated Ferritin

This patient has anemia of chronic disease (ACD) with functional iron deficiency, requiring investigation of the underlying inflammatory or malignant condition before initiating any iron or erythropoiesis-stimulating therapy. 1, 2

Diagnostic Interpretation

Your patient's laboratory pattern is pathognomonic for anemia of chronic disease:

• Elevated ferritin (720 ng/mL) with low iron saturation (23.25%) and low serum iron (31 mcg/dL) indicates functional iron deficiency where iron is sequestered in storage but unavailable for erythropoiesis 1, 2
• Low reticulocyte count (1.3%) with hemoglobin 9.8 g/dL confirms hypoproliferative anemia—the bone marrow is not responding appropriately to the anemia 3, 4
• Normocytic MCV (82.2 fL) rules out nutritional deficiencies as the primary cause 4, 5
• Markedly elevated B12 (1277 pg/mL) and normal folate (20 ng/mL) exclude megaloblastic anemia 1

The combination of increased ferritin with low iron saturation and low reticulocyte count is characteristic of inflammatory cytokine-mediated suppression of erythropoiesis and iron utilization 2, 5.

Immediate Diagnostic Workup Required

Before any treatment, you must identify the underlying chronic disease causing this anemia:

• Inflammatory markers: Check CRP and ESR to confirm active inflammation 4
• Renal function: Measure creatinine and calculate GFR, as chronic kidney disease commonly presents with normocytic anemia and low reticulocytes when GFR falls below 20-30 mL/min 4, 6
• Malignancy screening: The elevated ferritin with normocytic anemia raises concern for hematologic malignancy (myeloma, lymphoma, MDS) or solid tumors 1
• Peripheral blood smear: Essential to evaluate for dysplastic features, blasts, or abnormal cell morphology that would indicate myelodysplastic syndrome or other bone marrow disorders 1, 5
• Hemolysis markers: Check LDH, indirect bilirubin, and haptoglobin to exclude occult hemolysis, though the low reticulocyte count makes this less likely 3, 5

Critical Pitfall to Avoid

Do not supplement with oral or IV iron despite the low iron saturation. 1, 2 In anemia of chronic disease, iron is trapped in macrophages by hepcidin and cannot be mobilized for erythropoiesis. Adding more iron will only increase ferritin further without improving hemoglobin and may cause iron overload 2. Iron supplementation is only indicated when ferritin is <100 mcg/L in the setting of inflammation 4, 6.

When to Consider Bone Marrow Examination

Bone marrow aspiration and biopsy are indicated if: 1, 4

• Peripheral smear shows dysplastic features, blasts, or unexplained abnormalities
• Progressive anemia despite treatment of identified underlying conditions
• Concern for myelodysplastic syndrome (especially given the low reticulocyte response)
• Unexplained pancytopenia or abnormalities in multiple cell lines
• No identifiable cause after comprehensive noninvasive workup

The low reticulocyte count with normocytic anemia and high ferritin in a patient not on supplementation raises particular concern for MDS, which commonly presents with this pattern 1, 7.

Treatment Strategy

Treatment must target the underlying disease, not the anemia itself: 1, 2, 5

If Chronic Kidney Disease is Identified:

• Do not initiate erythropoiesis-stimulating agents (ESAs) until hemoglobin is <10 g/dL in asymptomatic patients 6, 5
• When ESAs are used, target the lowest dose sufficient to reduce transfusion need, not a specific hemoglobin target 6
• Supplemental iron therapy should be given when ferritin <100 mcg/L or transferrin saturation <20% during ESA therapy 6

If Inflammatory Condition is Identified:

• Treat the underlying inflammatory disease (autoimmune disorder, chronic infection, inflammatory bowel disease) 2, 5
• Monitor hemoglobin every 6 months for mild disease, more frequently for active disease 4
• Consider ESAs only if treating the underlying condition fails to improve anemia and hemoglobin remains <10 g/dL with symptoms 6, 2

If Myelodysplastic Syndrome is Diagnosed:

• Patients with low-risk MDS and severe anemia (Hb ≤10 g/dL) with serum erythropoietin ≤500 mU/dL should be treated with erythropoiesis-stimulating agents 1
• Hypomethylating agents (azacitidine or decitabine) are reserved for high-risk MDS with elevated blast counts 1, 7

Monitoring and Follow-up

• Recheck complete blood count in 4-6 weeks after initiating treatment of the underlying condition 4
• Do not transfuse unless hemoglobin drops below 7-8 g/dL or patient develops severe symptoms (chest pain, dyspnea at rest, hemodynamic instability) 5
• Serial reticulocyte counts can track response to therapy—rising counts indicate effective treatment 3

The key principle is that anemia of chronic disease severity correlates with the underlying disease severity, and treating the anemia without addressing the root cause is futile and potentially harmful 2, 5.