Initial Workup and Treatment for Anemia
The initial workup for anemia should include a complete blood count with red cell indices, reticulocyte count, peripheral blood smear, serum ferritin, transferrin saturation, and CRP, followed by targeted treatment based on the identified cause. 1
Diagnostic Approach
Step 1: Initial Laboratory Assessment
- Complete blood count (CBC) with:
- Hemoglobin level
- Red cell indices (MCV, MCH, RDW)
- White blood cell count and differential
- Platelet count
- Reticulocyte count
- Peripheral blood smear examination
- Serum ferritin level
- Transferrin saturation (TSAT)
- C-reactive protein (CRP) or other inflammatory markers 1
Step 2: Classification Based on MCV
Microcytic anemia (MCV < 80 fL):
Normocytic anemia (MCV 80-100 fL):
- If reticulocyte count is high: evaluate for hemolysis or blood loss
- LDH, haptoglobin, bilirubin, direct antiglobulin test
- If reticulocyte count is low/normal: consider anemia of chronic disease, renal disease, or early deficiency 2
- If reticulocyte count is high: evaluate for hemolysis or blood loss
Macrocytic anemia (MCV > 100 fL):
- Vitamin B12 and folate levels
- Liver function tests
- Thyroid function tests
- Review medication history (azathioprine, methotrexate)
- Consider alcohol use assessment 4
Step 3: Additional Testing Based on Initial Results
- If iron deficiency suspected: serum ferritin < 30 ng/mL is diagnostic
- If ferritin 30-100 ng/mL with elevated CRP: consider combined iron deficiency and anemia of chronic disease 1
- If B12 deficiency suspected: methylmalonic acid and homocysteine levels may be helpful
- If hemolysis suspected: LDH, haptoglobin, reticulocyte count, bilirubin 1
Treatment Algorithm
Iron Deficiency Anemia
Oral iron therapy:
IV iron:
Vitamin B12 Deficiency
Parenteral B12 therapy:
- Initial: 100 mcg daily intramuscularly for 6-7 days
- Followed by 100 mcg every 3-4 days until normalization
- Maintenance: 100 mcg monthly for life in pernicious anemia 6
Oral B12 supplementation:
- Option for patients with normal intestinal absorption
- Not reliable for pernicious anemia 6
Folate Deficiency
- Oral folate supplementation: 1-5 mg daily for 3-6 months 4
Anemia of Chronic Disease
- Treat underlying condition
- Consider erythropoiesis-stimulating agents if appropriate
- IV iron may be beneficial even with normal or elevated ferritin 5
Special Considerations
When to Consider Bone Marrow Examination
- Unexplained cytopenias
- Suspected myelodysplastic syndrome
- No response to appropriate therapy
- Abnormal cells on peripheral smear 4
When to Consider GI Evaluation
- Iron deficiency anemia in men or postmenopausal women
- No obvious source of blood loss
- Persistent anemia despite appropriate therapy 3
Follow-up Monitoring
- Repeat CBC in 4-8 weeks to assess response to treatment
- Expect hemoglobin increase of at least 2 g/dL with appropriate therapy
- For unexplained anemia, close follow-up with CBC every 6 months 4
Common Pitfalls to Avoid
- Treating anemia without identifying the underlying cause
- Missing concurrent iron deficiency in macrocytic anemia
- Relying solely on MCV to rule out vitamin deficiencies
- Overlooking medication effects on blood counts
- Failing to investigate alcohol use in macrocytic anemia 4
- Neglecting to consider anemia of chronic disease when ferritin is normal or elevated 1
By following this systematic approach to the workup and treatment of anemia, clinicians can efficiently identify the underlying cause and implement appropriate therapy to improve patient outcomes.