What is the initial workup and treatment for a patient presenting with anemia?

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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

  1. Microcytic anemia (MCV < 80 fL):

    • Iron studies (serum iron, TIBC, ferritin)
    • Consider hemoglobin electrophoresis if thalassemia suspected
    • RDW can help distinguish iron deficiency from thalassemia 2, 3
  2. 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
  3. 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

  1. Oral iron therapy:

    • First-line treatment: 100-200 mg elemental iron daily
    • Monitor response with hemoglobin check at 4 weeks
    • Continue for 3-6 months after normalization to replenish stores 1, 3
  2. IV iron:

    • Consider if oral iron not tolerated or ineffective
    • Indicated in patients with inflammatory bowel disease with active inflammation
    • More rapid correction of anemia than oral iron 1, 5

Vitamin B12 Deficiency

  1. 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
  2. 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.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Laboratory evaluation of anemia.

The Western journal of medicine, 1987

Research

Iron deficiency anemia.

American family physician, 2007

Guideline

Diagnosis and Management of Macrocytosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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