What is the appropriate management for a patient with normocytic anemia, as indicated by low hemoglobin and hematocrit levels, and a red blood cell count near the lower limit of normal, with no clear evidence of chronic blood loss or malabsorption?

Management of Normocytic Anemia with Borderline Low Hemoglobin

Based on your laboratory values showing mild normocytic anemia (hemoglobin 12.0-12.9 g/dL, hematocrit 38.3-40.7%, normal MCV 88.9-91.6 fL), you require a systematic diagnostic workup to identify the underlying cause before initiating treatment, as normocytic anemia typically indicates chronic disease, early iron deficiency, hemolysis, or bone marrow dysfunction rather than simple nutritional deficiency. 1

Initial Diagnostic Workup

Your immediate evaluation must include:

• Reticulocyte count to distinguish between decreased RBC production (low reticulocyte count) versus blood loss or hemolysis (high reticulocyte count) 2, 1
• Iron studies: serum ferritin, transferrin saturation (TfS), serum iron, and total iron-binding capacity 2, 1
  • Ferritin <30 μg/L indicates iron deficiency even without inflammation 1
  • With inflammation present, ferritin up to 100 μg/L may still represent iron deficiency 1
  • Transferrin saturation <16-20% suggests absolute iron deficiency 1
• Inflammatory markers: CRP and ESR to identify anemia of chronic disease 2, 1
• Vitamin B12 and folate levels, as combined deficiencies can present with normal MCV 2, 1
• Renal function tests (creatinine, BUN), since chronic kidney disease causes normocytic anemia when GFR falls below 20-30 mL/min 1
• Peripheral blood smear to evaluate for schistocytes, hypochromic cells, or abnormal white blood cells/platelets 1

Key Diagnostic Considerations

Red cell distribution width (RDW) is particularly important in your case:

• Your RDW values (11.9-13.1%) are normal, but a high RDW in normocytic anemia suggests underlying iron deficiency or combined deficiency states 2, 1
• Normal RDW with normocytic anemia points toward anemia of chronic disease, early renal insufficiency, or bone marrow dysfunction 1

Reticulocyte count interpretation:

• Low or "normal" reticulocytes indicate inability to respond properly to anemia due to deficiencies or primary bone marrow disease 2
• Elevated reticulocytes indicate increased red cell formation, excluding deficiencies and suggesting hemolysis or acute blood loss 2, 1

Common Causes to Investigate

Anemia of chronic disease is the most common cause of normocytic anemia, found in 6% of hospitalized adult patients 3:

• Characterized by low serum iron, low TIBC, ferritin >100 μg/L, and transferrin saturation <20% 1
• Inflammatory cytokines suppress erythropoietin production and directly inhibit erythropoiesis 1
• Critical pitfall: Do not assume anemia of chronic disease without measuring iron studies, as 25-37.5% of patients with chronic conditions have concurrent iron deficiency 1

Early or functional iron deficiency:

• Early nutritional deficiencies may initially present as normocytic anemia before morphological changes become apparent 1
• Your slightly low MCHC (31.3-31.7 g/dL) may suggest early iron-restricted erythropoiesis 2

Occult gastrointestinal blood loss:

• In men and post-menopausal women, GI blood loss is the most common cause of iron deficiency 2
• Perform stool guaiac testing for occult blood immediately if iron deficiency is identified 1
• If positive or if transfusion-dependent, proceed to upper endoscopy with small bowel biopsy and colonoscopy to exclude malignancy 2

Management Algorithm

Step 1: If reticulocyte count is LOW:

• Proceed with iron studies, B12/folate, renal function, and inflammatory markers 1
• If ferritin <30 μg/L or <100 μg/L with inflammation: treat as iron deficiency and investigate for GI blood loss 2, 1
• If ferritin >100 μg/L with low TSAT and elevated CRP: anemia of chronic disease—treat underlying inflammatory condition 1
• If renal insufficiency with creatinine ≥2 mg/dL and no other cause identified: likely erythropoietin deficiency 1

Step 2: If reticulocyte count is HIGH:

• Investigate for hemolysis: indirect/direct bilirubin, haptoglobin, LDH, direct antiglobulin test (Coombs) 1
• Evaluate for acute or chronic blood loss with stool guaiac and medication review (NSAIDs, anticoagulants) 1

Step 3: If initial workup is unrevealing:

• Consider bone marrow aspiration and biopsy, particularly if pancytopenia or other cytopenias are present 1
• Review medications for bone marrow suppression (antibiotics, chemotherapy, immunosuppressants) 1
• Consider hematology consultation 2

Treatment Principles

Do not initiate empiric treatment without identifying the underlying cause 2:

• Iron supplementation is only appropriate if iron deficiency is confirmed 2
• Treating presumed iron deficiency without confirmation may mask serious underlying conditions like GI malignancy 2
• All correctable causes should be addressed before considering erythropoietin-stimulating agents 2

Monitoring response:

• Lack of response to appropriate nutritional supplementation suggests alternative or additional diagnoses requiring further investigation 1
• Even mild anemia is associated with reduced exercise capacity, impaired quality of life, and increased hospitalization risk 1