What is the approach to diagnosing and treating anemia?

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Last updated: September 21, 2025View editorial policy

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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

  1. 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
  2. Intravenous iron for:

    • Poor absorption
    • Intolerance to oral iron
    • Severe deficiency requiring rapid repletion 1
  3. Investigate and treat underlying cause:

    • GI bleeding (endoscopy may be indicated)
    • Menstrual blood loss
    • Malabsorption disorders 2

Anemia of Chronic Disease

  1. Treat underlying inflammatory condition
  2. Consider iron supplementation if concurrent iron deficiency exists
  3. 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

  1. Correct deficiency:
    • B12: 1000 μg IM initially, then monthly or oral supplementation
    • Folate: 1-5 mg daily orally 2
  2. Treat underlying cause (malabsorption, dietary deficiency)

Anemia Due to Chronic Kidney Disease

  1. ESAs when hemoglobin <10 g/dL
  2. Target hemoglobin: 10-11 g/dL (avoid exceeding 11 g/dL)
  3. Monitor iron status and supplement as needed 3

Anemia Due to Chemotherapy

  1. ESAs only when:
    • Hemoglobin <10 g/dL
    • Treatment is not curative
    • At least 2 months of planned chemotherapy remains 3
  2. 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

  1. Accepting dietary history as sole cause of IDA without GI investigation
  2. Misinterpreting ferritin levels in the presence of inflammation (may be falsely normal or elevated)
  3. Inadequate duration of iron therapy
  4. Deferring iron replacement while awaiting investigations 1
  5. Assuming constipation is caused by anemia without investigating other causes 1
  6. 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

References

Guideline

Iron Deficiency Anemia Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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