What is the approach to diagnosing and managing anemia?

Diagnostic and Management Approach to Anemia

Initial Classification by MCV

Begin anemia evaluation by classifying based on mean corpuscular volume (MCV) after confirming hemoglobin < 13 g/dL in men or < 12 g/dL in non-pregnant women, then use reticulocyte count to distinguish production defects from destruction or loss. 1, 2

Microcytic Anemia (MCV < 80 fL)

• Iron deficiency anemia is diagnosed when serum ferritin < 30 μg/L without inflammation, or up to 100 μg/L in the presence of inflammation (measure CRP to assess inflammatory state). 1, 2

• Anemia of chronic disease/inflammation should be suspected when ferritin > 100 μg/L with transferrin saturation (TSAT) < 20% and elevated CRP. 1

• Thalassemia should be evaluated with hemoglobin electrophoresis if iron studies are normal. 1

• Genetic disorders of iron metabolism (sideroblastic anemia, IRIDA, hemochromatosis) should be suspected when ferritin is elevated AND TSAT is elevated, or when TSAT is low with ferritin 20-100 μg/L. 1

Normocytic Anemia (MCV 80-100 fL)

• Consider acute blood loss, hemolysis, anemia of chronic disease, or early iron deficiency as potential causes. 1

• Anemia of chronic disease can be normocytic in 50-70% of cases, associated with malignancy, chronic infection, or autoimmune disease. 2

• Renal anemia is characterized by inappropriately low endogenous erythropoietin levels; assess creatinine and GFR. 2

Macrocytic Anemia (MCV > 100 fL)

• Vitamin B12 deficiency requires measurement of serum B12 and methylmalonic acid for confirmation. 1, 2

• Folate deficiency is diagnosed with serum folate levels, though now rare in developed countries. 2

• Consider medications, alcohol use, or myelodysplastic syndrome as additional causes. 1

Essential Laboratory Workup

• Order CBC with MCV and RDW, reticulocyte count, serum ferritin, transferrin saturation, and CRP as the initial diagnostic panel. 1, 2

• High RDW suggests iron deficiency anemia or combined deficiencies (masked by coexisting microcytosis and macrocytosis producing falsely normal MCV). 2

• Reticulocyte count distinguishes impaired production (low reticulocytes) from increased destruction or blood loss (high reticulocytes). 1, 2

Critical Diagnostic Pitfalls

• Ferritin interpretation in inflammation: In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency; always measure CRP to assess inflammation. 1

• Masked combined deficiencies: When microcytosis and macrocytosis coexist (e.g., combined iron and B12 deficiency), MCV may appear falsely normal; elevated RDW is the key clue. 2

• Elderly patients: Never attribute anemia to normal aging; comprehensive evaluation is necessary to identify treatable causes. 1

Special Population Considerations

Chronic Kidney Disease

• Monitor hemoglobin every 3 months when GFR < 30 mL/min. 1

• Perform complete workup if hemoglobin < 12 g/dL in women or < 13 g/dL in men. 1

• Treat iron deficiency first; consider erythropoietin therapy if anemia persists despite iron repletion. 1

Inflammatory Bowel Disease

• Anemia is typically multifactorial (iron deficiency from blood loss plus anemia of chronic disease). 1

• Use disease-specific ferritin thresholds: < 30 μg/L without inflammation, up to 100 μg/L with inflammation. 1

• If ferritin is 30-100 μg/L, suspect combination of true iron deficiency and anemia of chronic disease. 1

• Screen regularly with CBC, CRP, and serum ferritin based on disease activity. 1

Iron Deficiency Anemia Requiring GI Evaluation

• All adults with confirmed iron deficiency anemia require urinalysis/urine microscopy, celiac disease screening, and in appropriate cases, upper and lower GI endoscopy to identify the source of blood loss. 1

Treatment Approach by Etiology

Iron Deficiency Anemia

• Treat with oral or intravenous iron supplementation and investigate the source of blood loss. 1, 2

Anemia of Chronic Disease/Inflammation

• Primary treatment involves addressing the underlying condition; use intravenous iron and erythropoiesis-stimulating agents as needed. 1, 2

Vitamin B12 Deficiency (Pernicious Anemia)

• Parenteral vitamin B12 is required for life (oral form is not dependable for pernicious anemia). 3

• Administer 100 mcg daily IM or deep subcutaneous for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks. 3

• Maintenance: 100 mcg monthly for life. 3

• Administer folic acid concomitantly if needed. 3

Severe Anemia

• May require red blood cell transfusion followed by intravenous iron supplementation. 2