What is the best course of action for a patient with persistent anemia, as indicated by low red blood cell count, hemoglobin, and hematocrit levels?

Management of Persistent Normocytic Anemia

This patient requires a comprehensive diagnostic workup to identify the underlying cause of persistent normocytic anemia before initiating any treatment, with particular attention to iron studies (including ferritin and transferrin saturation), reticulocyte count, vitamin B12, folate levels, and assessment for occult blood loss or chronic disease. 1

Immediate Diagnostic Priorities

Essential Laboratory Testing

• Iron studies are mandatory despite normal-appearing MCV, as serum ferritin and transferrin saturation must be checked to assess both absolute and functional iron deficiency, with ferritin <30 μg/L indicating iron deficiency in the absence of inflammation 1
• Reticulocyte count is crucial to distinguish between production defects (low/normal reticulocytes suggesting inadequate bone marrow response) versus hemolysis or acute blood loss (elevated reticulocytes) 1
• Vitamin B12 and folate levels are necessary because nutritional deficiencies can present with normocytic anemia early in their course before progressing to macrocytic anemia 1
• Renal function assessment (creatinine, urea) is essential as chronic kidney disease commonly causes normocytic anemia 2

Critical Diagnostic Considerations

• The slightly low MCHC values (30.6-31.2 g/dL, below normal range of 31.6-35.4 g/dL) suggest possible functional iron deficiency or hemoglobinization defect that warrants iron studies even if ferritin appears normal 3
• Normal hemoglobin and hematocrit ranges do not exclude iron depletion, as these parameters decrease only when severe iron depletion is present and individuals can be iron-depleted despite normal CBC indices 3
• Medication history review for NSAIDs, immunosuppressants, and other drugs affecting blood counts is essential 2

Differential Diagnosis Based on Pattern

Anemia of Chronic Disease

• Consider inflammatory conditions if ferritin is elevated with low transferrin saturation, indicating functional iron deficiency where iron is sequestered despite adequate stores 1, 4
• Hepcidin-mediated iron restriction in chronic inflammation can present with normocytic anemia and requires addressing the underlying inflammatory condition 4

Occult Blood Loss

• Gastrointestinal investigation should be considered even with normal iron studies if true anemia is confirmed, as occult GI blood loss from malignancy can present before iron stores are depleted 2
• Screening for coeliac disease with tissue transglutaminase antibody testing is recommended, as malabsorption can cause anemia before overt iron deficiency develops 2

Hemolysis Evaluation

• If reticulocyte count is elevated, check haptoglobin, lactate dehydrogenase, and bilirubin to exclude hemolysis 2

Treatment Algorithm

Iron Deficiency Management

• Treat iron deficiency regardless of underlying cause once identified, with oral iron supplementation as first-line for most patients 1
• Address functional iron deficiency by treating the underlying inflammatory condition and considering iron supplementation even with elevated ferritin if transferrin saturation is low 1

Monitoring Strategy

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually if stable 2
• Further investigation is warranted if hemoglobin cannot be maintained or continues to decline despite addressing identified causes 2

Referral Indications

Hematology Consultation Required

• Abnormalities in multiple cell lines (cytopenias affecting WBC, RBC, or platelets) warrant hematology referral 1
• Unexplained normocytic anemia after complete workup requires further evaluation and potential referral 1
• Lack of response to appropriate therapy after addressing identified deficiencies necessitates specialist evaluation 1

Critical Pitfalls to Avoid

• Do not rely solely on CBC parameters without measuring iron status indicators, as many cases of iron depletion are missed and misdiagnosed as normal when only hemoglobin and hematocrit are checked 3
• Do not assume normal MCV excludes iron deficiency, as early iron deficiency and functional iron deficiency can present with normocytic indices 1, 3
• Do not initiate erythropoiesis-stimulating agents without first ensuring adequate iron repletion, as this increases risk of thromboembolism, hypertension, and seizures 1