What is the initial workup and management for a 59-year-old male with chronic normocytic anemia?

Workup of Chronic Normocytic Anemia in a 59-Year-Old Male

Begin with a complete blood count including reticulocyte count, comprehensive metabolic panel with renal function, iron studies (serum ferritin, transferrin saturation, serum iron, TIBC), inflammatory markers (CRP, ESR), vitamin B12, folate, and peripheral blood smear. 1

Initial Laboratory Assessment

The reticulocyte count is your critical first branch point—it distinguishes between decreased red blood cell production versus appropriate marrow response to blood loss or hemolysis 1, 2:

• Low reticulocyte count (<2% corrected): Indicates decreased erythrocyte production, pointing toward bone marrow failure, nutritional deficiencies in early stages, chronic kidney disease, or anemia of chronic inflammation 1, 3

• High reticulocyte count (>2% corrected): Suggests active blood loss or hemolysis, requiring immediate investigation for these causes 1, 2

Essential Baseline Studies

Obtain these tests simultaneously with the reticulocyte count 1:

• Iron studies: Serum ferritin, transferrin saturation (TSAT), serum iron, and total iron-binding capacity (TIBC) 4, 1

  • In the absence of inflammation, ferritin <30 μg/L indicates iron deficiency 4
  • With inflammation present, ferritin up to 100 μg/L may still represent iron deficiency 4
  • TSAT <16% suggests absolute iron deficiency in the general population 4

• Renal function: Serum creatinine and estimated GFR 1

  • Normocytic anemia typically develops when GFR falls below 20-30 mL/min due to erythropoietin deficiency 1

• Inflammatory markers: CRP and ESR to identify chronic inflammation 1

• Vitamin levels: B12 and folate, as combined deficiency states can present with normal MCV 1

• Peripheral blood smear: Evaluate for schistocytes (hemolysis), hypochromic cells (iron deficiency), or abnormal white blood cells/platelets (bone marrow disorder) 4

Directed Investigation Based on Initial Findings

If Iron Deficiency is Identified

Perform stool guaiac testing for occult gastrointestinal bleeding immediately 4, 1. This is the most common cause of iron deficiency requiring identification. Consider upper and lower endoscopy if occult blood is positive or clinical suspicion is high 4.

If Reticulocytes are Elevated (>2%)

Investigate for hemolysis with 1, 2:

• Physical examination for jaundice and hepatosplenomegaly
• Indirect and direct bilirubin (unconjugated hyperbilirubinemia suggests hemolysis)
• Haptoglobin (decreased in hemolysis)
• LDH (elevated in hemolysis)
• Direct antiglobulin test (Coombs test)
• Peripheral smear for schistocytes

If Renal Insufficiency is Present (Creatinine ≥2 mg/dL)

The anemia is likely due to erythropoietin deficiency if no other cause is identified 1. Serum erythropoietin levels are generally not indicated but can be measured if the diagnosis is uncertain 1.

If Chronic Inflammation is Present

Anemia of chronic disease is characterized by ferritin >100 μg/L and TSAT <20% 4. If ferritin is between 30-100 μg/L, suspect combined iron deficiency and anemia of chronic disease 4. This is a normocytic, normochromic anemia caused by inflammatory cytokines suppressing erythropoietin production 1, 5.

Red Cell Distribution Width (RDW) Interpretation

A high RDW in normocytic anemia suggests underlying iron deficiency or a mixed deficiency state 1. This finding warrants more aggressive investigation for iron deficiency even if initial iron studies appear borderline.

When to Consider Bone Marrow Biopsy

Perform bone marrow aspiration and biopsy when unexplained pancytopenia or other cytopenias are present, or when initial workup fails to identify a cause 1. Look specifically for:

• Myelodysplastic syndrome
• Aplastic anemia
• Bone marrow infiltration (malignancy)
• Megaloblastic changes despite normal B12/folate levels

Additional Considerations for This Patient Population

In a 59-year-old male, prioritize evaluation for 1, 2:

• Occult malignancy: Age-appropriate cancer screening if not up to date
• Chronic kidney disease: Common in this age group and frequently overlooked
• Medication review: NSAIDs, antibiotics, and other drugs can cause bone marrow suppression or hemolysis 4
• Alcohol use: Can cause normocytic anemia through multiple mechanisms

Common Pitfalls to Avoid

• Do not assume anemia of chronic disease without measuring iron studies—up to 25-37.5% of patients with chronic kidney disease have concurrent iron deficiency 4
• Do not overlook combined deficiency states (iron + B12/folate) which present with normal MCV but require treatment of both deficiencies 1
• Do not delay gastrointestinal evaluation in iron deficiency—occult GI bleeding is the most common cause and may represent serious pathology 4, 1
• Do not measure erythropoietin levels routinely—they add little diagnostic value except when renal insufficiency is present without other explanation 1