Approach to Diagnosing and Treating Anemia
The optimal approach to anemia requires a systematic diagnostic classification based on morphology (MCV) and reticulocyte count, followed by targeted testing and treatment of the underlying cause. 1
Diagnostic Approach
Step 1: Initial Evaluation
- Complete Blood Count (CBC) with differential
- Classify anemia based on Mean Corpuscular Volume (MCV):
- Microcytic (MCV <80 fL)
- Normocytic (MCV 80-100 fL)
- Macrocytic (MCV >100 fL) 2
Step 2: Reticulocyte Count Assessment
- Calculate reticulocyte index (RI) to determine if anemia is due to decreased production or increased loss/destruction
- Low RI (<1.0): Indicates decreased RBC production
- High RI (>2.0): Indicates blood loss or hemolysis 2
Step 3: Targeted Testing Based on Classification
For Microcytic Anemia:
- Iron studies: serum ferritin, serum iron, TIBC, transferrin saturation
- Hemoglobin electrophoresis if iron studies normal (to rule out thalassemia)
- Consider lead levels in children 2, 1
For Normocytic Anemia:
- Review medication list for drug-induced anemia
- Evaluate for chronic disease, kidney disease, or endocrine disorders
- Consider bone marrow examination if other tests inconclusive 2
For Macrocytic Anemia:
- Vitamin B12 and folate levels
- Liver function tests
- Thyroid function tests
- Consider alcohol use assessment 2
Differential Diagnosis Framework
| Parameter | Iron Deficiency | Thalassemia Trait | Anemia of Chronic Disease |
|---|---|---|---|
| MCV | Low | Very low (<70 fl) | Low/Normal |
| RDW | High (>14%) | Normal (≤14%) | Normal/Slightly elevated |
| Ferritin | Low (<30 μg/L) | Normal | Normal/High |
| TSAT | Low | Normal | Low |
| RBC count | Normal/Low | Normal/High | Normal/Low |
Treatment Approach
Iron Deficiency Anemia
Oral iron supplementation with 35-65 mg of elemental iron daily is the first-line treatment 1
- Options: ferrous sulfate, ferrous fumarate, or ferrous gluconate
- Continue for 3 months after hemoglobin normalization to replenish stores
- Monitor hemoglobin weekly until stable, then monthly
Intravenous iron for:
- Poor absorption
- Intolerance to oral iron
- Severe deficiency requiring rapid repletion 1
Investigate and treat underlying cause:
- GI bleeding (endoscopy may be indicated)
- Menstrual blood loss
- Malabsorption disorders 2
Anemia of Chronic Disease
- Treat underlying inflammatory condition
- Consider iron supplementation if concurrent iron deficiency exists
- Erythropoiesis-stimulating agents (ESAs) may be considered when:
- Anemia is due to chronic kidney disease
- Anemia is due to chemotherapy in cancer patients
- Anemia is due to zidovudine in HIV patients 3
Vitamin B12/Folate Deficiency
- Correct deficiency:
- B12: 1000 μg IM initially, then monthly or oral supplementation
- Folate: 1-5 mg daily orally 2
- Treat underlying cause (malabsorption, dietary deficiency)
Anemia Due to Chronic Kidney Disease
- ESAs when hemoglobin <10 g/dL
- Target hemoglobin: 10-11 g/dL (avoid exceeding 11 g/dL)
- Monitor iron status and supplement as needed 3
Anemia Due to Chemotherapy
- ESAs only when:
- Hemoglobin <10 g/dL
- Treatment is not curative
- At least 2 months of planned chemotherapy remains 3
- Discontinue ESAs after completion of chemotherapy course
Monitoring and Follow-up
- Hemoglobin: Check weekly until stable, then monthly
- Iron parameters: Monitor regularly during treatment
- Expected improvement: 1-2 g/dL increase in hemoglobin within 2-4 weeks of starting iron therapy 1
Common Pitfalls to Avoid
- Accepting dietary history as sole cause of IDA without GI investigation
- Misinterpreting ferritin levels in the presence of inflammation (may be falsely normal or elevated)
- Inadequate duration of iron therapy
- Deferring iron replacement while awaiting investigations 1
- Assuming constipation is caused by anemia without investigating other causes 1
- Failing to evaluate for occult malignancy in men and postmenopausal women with iron deficiency anemia 1
Special Considerations
- Pregnant women, infants, elderly, and athletes have higher iron requirements
- Heart failure patients may have iron deficiency without anemia
- Consider hereditary hemorrhagic telangiectasia in recurrent iron deficiency 1