What is the diagnosis and treatment approach for a patient with suspected anemia?

Diagnosis and Treatment of Anemia

Begin with a complete blood count (CBC) with indices and peripheral blood smear to classify anemia by mean corpuscular volume (MCV), then direct treatment toward the specific underlying cause—iron deficiency receives oral or intravenous iron, vitamin B12/folate deficiencies receive replacement therapy, and anemia of chronic disease requires treatment of the underlying inflammatory condition. 1, 2, 3

Diagnostic Algorithm

Initial Laboratory Workup

• Obtain CBC with differential and red cell indices to characterize the anemia and identify other cytopenias 1, 2
• Classify by MCV: Microcytic (MCV <80 fL), normocytic (MCV 80-100 fL), or macrocytic (MCV >100 fL) 2, 3
• Peripheral blood smear confirms RBC morphology, size, shape, and color 1, 2
• Reticulocyte count and index assess bone marrow response: low index indicates decreased production; high index suggests blood loss or hemolysis 3

Iron Studies and Inflammatory Markers

• Comprehensive iron panel: serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), and ferritin 3
• Absolute iron deficiency: TSAT <15% AND ferritin <30 ng/mL 3
• Functional iron deficiency (anemia of chronic disease): ferritin >100 μg/L with TSAT <20% 3
• In the presence of inflammation, ferritin <100 μg/L with TSAT <16% suggests iron deficiency, while ferritin >100 μg/L with TSAT <16% indicates anemia of chronic disease 4
• Measure inflammatory markers (CRP, ESR) since ferritin is an acute-phase reactant and can be falsely elevated during inflammation 4

Additional Testing for Macrocytic Anemia

• Measure vitamin B12 and folate levels when MCV is elevated 4
• In doubtful cases, homocysteine (elevated in B12 or folate deficiency) and methylmalonic acid (specific for B12 deficiency) provide greater sensitivity than serum B12 alone 4

Assess for Blood Loss

• Check stool and urine for occult blood to identify ongoing losses 1

Treatment Algorithm by Etiology

Iron Deficiency Anemia

• First-line: Oral iron supplementation with ferrous sulfate 324 mg (65 mg elemental iron) daily or twice daily between meals 1, 2
• Add ascorbic acid 250-500 mg twice daily to enhance absorption 1
• Continue treatment for 2-3 months after hemoglobin normalization to replenish iron stores 1, 2
• Recheck hemoglobin at 4 weeks: an increase ≥1 g/dL confirms the diagnosis and adequate response 2, 3

Intravenous iron is indicated when:

• Oral iron is not tolerated 1, 2
• Malabsorption is present 1, 2
• Rapid repletion is needed 1, 2
• Active inflammatory bowel disease is present 2

Vitamin B12 and Folate Deficiency

• Treat deficiencies to avoid anemia, particularly in patients with ileal resection or small bowel disease 4
• For pernicious anemia: parenteral vitamin B12 is required for life; oral forms are not dependable 5
• Dosing for pernicious anemia: 100 mcg intramuscular or deep subcutaneous injection daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life 5
• Monitor vitamin B12 and folate levels at least annually, or if macrocytosis is present 4

Anemia of Chronic Disease

• Treat the underlying inflammatory condition first to enhance iron absorption and reduce iron depletion 2, 3
• Optimization of disease-specific therapy (e.g., infliximab for inflammatory bowel disease) can significantly improve hemoglobin levels 4
• Intravenous iron may be needed despite treating inflammation 2
• Erythropoiesis-stimulating agents (ESAs) may be considered only after optimizing disease therapy and with insufficient response to IV iron, targeting hemoglobin ≤12 g/dL 4

Transfusion Therapy

Reserve transfusions for specific situations:

• Hemoglobin <7 g/dL as a general threshold 4, 1
• Above 7 g/dL if symptoms or particular risk factors are present (hemodynamic instability, severe acute anemia, coronary heart disease) 4, 1
• Use restrictive transfusion strategy with trigger threshold of 7-8 g/dL in most hospitalized patients 1, 2
• Follow transfusions with subsequent intravenous iron supplementation since transfusions do not correct the underlying pathology and have no lasting effect 4

Monitoring and Follow-Up

• Repeat hemoglobin after 4 weeks of iron treatment to confirm response 1, 2, 3
• Monitor hemoglobin every 3 months for 1 year, then annually after successful treatment 1
• Anemia recurs in >50% of patients within one year, often indicating ongoing inflammation 4, 3
• For patients in remission, check hemoglobin every 12 months; for mild active disease, every 6 months 4, 3
• Administer additional iron if hemoglobin or MCV fall below normal 1

Common Pitfalls to Avoid

• Do not rely solely on ferritin in the presence of inflammation—it is an acute-phase reactant and can be falsely elevated; use TSAT and inflammatory markers together 4
• Do not use oral iron in patients with active inflammatory bowel disease—intravenous iron is more effective 2
• Do not use ESAs without first optimizing treatment of the underlying inflammatory condition and ensuring adequate iron stores 4
• Avoid overreliance on transfusions—they are a temporary fix that does not address the underlying cause and should be followed by iron supplementation 4, 1
• Do not stop iron therapy when hemoglobin normalizes—continue for 2-3 months to replenish stores 1, 2
• Recognize that multiple causes of anemia can coexist in the same patient, requiring comprehensive evaluation 4