What is the initial approach to treating anemia?

Initial Approach to Treating Anemia

The initial approach to treating anemia must begin with identifying and correcting reversible causes before considering any pharmacologic therapy—this means conducting a thorough diagnostic workup to determine whether the anemia stems from production defects, destruction, or blood loss, and addressing nutritional deficiencies, bleeding sources, or underlying diseases first. 1

Step 1: Identify Correctable Causes Before Treatment

The foundation of anemia management is determining etiology, not simply treating the hemoglobin number. 1

Essential Initial Workup

Conduct these investigations systematically: 1

• Complete drug exposure history to identify myelosuppressive agents or medications causing hemolysis 1
• Peripheral blood smear review (and bone marrow examination when indicated) to assess RBC morphology and production 1
• Iron studies: serum iron, total iron-binding capacity (TIBC), transferrin saturation, and ferritin 1
  • Transferrin saturation <15% and ferritin <30 ng/mL confirms absolute iron deficiency 1
  • Critical caveat: In the presence of inflammation (elevated CRP/ESR), ferritin <100 μg/L suggests iron deficiency, as inflammation falsely elevates ferritin 1
• Vitamin B12 and folate levels when macrocytosis is present or neurologic symptoms exist 1
  • Note: Folate deficiency is rare (<1%) in the US due to grain fortification; B12 deficiency occurs in only 3.9% of cancer patients 1
• Reticulocyte count and index to distinguish production defects (low RI <1.0) from blood loss/hemolysis (high RI >2.0) 1, 2
• Assess for occult blood loss: stool guaiac testing, endoscopy if indicated 1
• Renal function assessment to identify chronic kidney disease as a contributor 1
• Coombs testing for patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or autoimmune disease history 1

Physical Examination Clues

Look for specific findings that suggest underlying causes: 3

• Iron deficiency: angular stomatitis, glossitis, koilonychia (spoon nails), pagophagia (ice craving), blue sclerae 3
• Hemolysis: jaundice, splenomegaly 3
• Bleeding: petechiae, telangiectasias (suggesting hereditary hemorrhagic telangiectasia) 3
• Cardiovascular compensation: tachycardia, systolic flow murmurs, signs of heart failure 3

Step 2: Treat the Underlying Cause First

Address the root cause before symptomatic treatment: 1

For Iron Deficiency Anemia

• Oral iron supplementation: 100-200 mg elemental iron daily (e.g., ferrous sulfate 324 mg contains 65 mg elemental iron) 4, 5
  • Expect 3-6 months of therapy to normalize hemoglobin and replenish stores 5
  • Lower doses if gastrointestinal side effects occur 5
• Intravenous iron is preferred when: 1, 6, 5
  • Oral iron is not tolerated or causes significant GI side effects
  • Intestinal malabsorption is present (celiac disease, inflammatory bowel disease, post-bariatric surgery)
  • Rapid response is needed
  • Active inflammation is present (oral iron may exacerbate IBD through reactive oxygen species) 1

For Inflammatory/Chronic Disease Anemia

• Treat the underlying inflammatory condition (e.g., active ulcerative colitis, cancer) as the primary intervention 1
• Treating inflammation alone rarely normalizes hemoglobin; concurrent iron supplementation is usually necessary 1

For Nutritional Deficiencies

• Vitamin B12 deficiency: replacement therapy when confirmed 1
• Folate deficiency: supplementation (though rarely needed in the US) 1

For Blood Loss

• Identify and control bleeding sources: endoscopy for GI bleeding, gynecologic evaluation for menorrhagia 1, 5
• Consider bidirectional endoscopy (gastroscopy and colonoscopy) for unexplained iron deficiency anemia, especially in men and postmenopausal women 5

Step 3: Determine Need for Immediate Intervention

Do not use hemoglobin thresholds alone to trigger transfusion—assess symptoms, comorbidities, and clinical context: 1

Three Clinical Categories for Decision-Making

1. Asymptomatic without significant comorbidities: Observation and periodic reevaluation while treating underlying cause 1

2. Asymptomatic with comorbidities or high risk (cardiovascular disease, pulmonary disease, cerebrovascular disease): Consider RBC transfusion 1

3. Symptomatic anemia (fatigue limiting function, dyspnea, tachycardia, hemodynamic instability): Transfuse packed RBCs 1, 6

Transfusion Considerations

• Packed RBCs are preferred over whole blood 1
• Transfusion should be judicious and reserved for severe, symptomatic anemia with hemodynamic instability 6
• Acute onset anemia produces more pronounced symptoms than gradual onset due to lack of physiologic compensation 1

Step 4: Long-Term Monitoring

Monitor for recurrence, which occurs in >50% of patients within one year: 1

• Patients in remission: check hemoglobin every 12 months 1
• Patients with mild active disease: check every 6 months 1
• Vitamin B12 and folate: check annually or when macrocytosis develops 1

Critical Pitfalls to Avoid

• Never assume a single cause without comprehensive evaluation—anemia is often multifactorial 1
• Do not rely on ferritin alone in the presence of inflammation; use CRP/ESR to interpret iron studies correctly 1
• Avoid intramuscular iron—no evidence it is safer or more effective than oral or IV routes 1
• Do not initiate erythropoiesis-stimulating agents (ESAs) without first excluding and treating reversible causes 1
• Do not overlook renal insufficiency as a contributor, especially in elderly or cancer patients 1