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 red cell indices to classify anemia by mean corpuscular volume (MCV) as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL), then obtain a reticulocyte count to distinguish decreased production from blood loss or hemolysis, and proceed with targeted iron studies and peripheral blood smear to identify the specific etiology. 1, 2, 3

Diagnostic Algorithm

Initial Laboratory Assessment

• Obtain CBC with differential and red cell indices to characterize the anemia and identify other cytopenias 1, 2
• Check reticulocyte count and index: Low reticulocyte index indicates decreased bone marrow production; high index suggests blood loss or hemolysis 2, 3
• Review peripheral blood smear to confirm RBC size, shape, and color abnormalities 1, 2
• Assess for occult blood loss in stool and urine 1

Iron Studies Interpretation

• Order comprehensive iron panel: serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), and ferritin 2, 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% 2, 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

Additional Testing for Macrocytic Anemia

• Measure vitamin B12 and folate levels when MCV is elevated 4
• In doubtful cases, measure homocysteine (elevated in B12 or folate deficiency) or methylmalonate (specific for B12 deficiency with better sensitivity than serum B12) 4

Treatment Approach 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 iron absorption 1
• Continue treatment for 2-3 months after hemoglobin normalization to replenish iron stores 1, 2
• Recheck hemoglobin after 4 weeks: An increase ≥1 g/dL or hematocrit ≥3% confirms the diagnosis 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

Anemia of Chronic Disease

• Treat the underlying inflammatory condition first to enhance iron absorption and reduce iron depletion 2, 3
• Optimize disease-specific therapy before considering erythropoiesis-stimulating agents (ESAs), as anemia of chronic disease indicates active inflammation 4
• Consider ESAs only after insufficient response to intravenous iron and optimized disease therapy, with target hemoglobin not above 12 g/dL 4

Vitamin B12 and Folate Deficiency

• Treat deficiencies to avoid anemia, particularly in patients with small bowel disease or ileal resection 4
• For pernicious anemia: Administer 100 mcg vitamin B12 intramuscularly or deep subcutaneously 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
• Avoid intravenous route as almost all vitamin will be lost in urine 5
• Administer folic acid concomitantly if needed 5

Transfusion Therapy

Reserve red blood cell transfusion for specific situations:

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

Monitoring and Follow-Up

• Repeat hemoglobin after 4 weeks of iron treatment to assess response 1, 2, 3
• Monitor hemoglobin every 12 months in patients in remission 4, 3
• Monitor every 6 months in patients with mild active disease 4, 3
• Check vitamin B12 and folate levels at least annually or if macrocytosis is present 4
• Recurrence occurs in >50% of patients within one year, warranting long-term surveillance 4, 3

Critical Pitfalls to Avoid

• Do not rely solely on hemoglobin level for transfusion decisions; consider comorbidity and symptoms 4
• Do not use ESAs without considering risks including hypertension, thromboembolism, and potential tumor progression in cancer patients 1
• Do not overlook inflammatory status when interpreting ferritin levels, as ferritin is an acute-phase reactant and can be falsely elevated in inflammation 4
• Do not fail to identify and treat the underlying cause, as this leads to recurrence 1, 3
• Do not use oral vitamin B12 for pernicious anemia, as it is not dependable and parenteral administration is required for life 5