What is the workup for a patient presenting with leukopenia?

Diagnostic Workup for Leukopenia

The diagnostic workup for leukopenia should include a complete blood count with differential, peripheral blood smear review, and bone marrow examination with flow cytometry, cytogenetic analysis, and molecular testing if the cause is not immediately apparent from history or initial testing. 1

Initial Assessment

• Complete Blood Count with Differential

  • Confirm leukopenia (WBC < 4,000/μL)
  • Determine which cell lines are affected (neutropenia, lymphopenia, or both)
  • Check for concurrent anemia or thrombocytopenia (suggesting bone marrow involvement)

• Peripheral Blood Smear Review

  • Essential for accurate diagnosis 1
  • Evaluate neutrophil morphology and maturation
  • Look for morphological abnormalities, dysplasia, or blast cells
  • Check for presence of toxic granulations, Döhle bodies (suggesting infection)

• Review Previous CBC Results

  • Determine if leukopenia is acute or chronic
  • Assess pattern and progression of cell count changes 2

Laboratory Studies

• Blood Chemistry Profile

  • Comprehensive metabolic panel
  • Lactate dehydrogenase (LDH)
  • Coagulation studies (PT, PTT, fibrinogen) 1

• Infectious Disease Workup

  • Viral studies: HIV, hepatitis, EBV, CMV
  • Blood cultures if febrile
  • Specific testing based on clinical presentation (TB, malaria) 1, 3

• Autoimmune Evaluation

  • ANA and other autoimmune markers if clinically indicated
  • Rheumatoid factor, anti-CCP antibodies 1

Advanced Diagnostic Testing

• Bone Marrow Examination

  • Indicated when:

    • Cause is not apparent from initial testing
    • Multiple cell lines are affected
    • Abnormal cells are seen on peripheral smear
    • Persistent unexplained leukopenia 4, 1

  • Components:

    • Bone marrow aspirate and biopsy
    • Flow cytometry for immunophenotyping
    • Cytogenetic analysis (karyotype)
    • FISH testing for specific abnormalities
    • Molecular genetic testing for mutations 4, 1

• Imaging Studies

  • Chest X-ray to rule out infection or malignancy
  • CT scan if lymphadenopathy or organomegaly is present
  • Consider PET/CT if lymphoma is suspected 4

Special Considerations

• Medication Review

  • Comprehensive medication history
  • Focus on chemotherapeutic agents, antibiotics, antipsychotics, anticonvulsants
  • Consider drug-induced neutropenia 1, 5

• Urgent Management for Severe Neutropenia

  • Immediate action required for ANC < 500/μL with fever (≥38.3°C)
  • Broad-spectrum antibiotics
  • Hospital admission
  • Close monitoring for sepsis 1, 6

• Referral Considerations

  • Hematology consultation for persistent unexplained leukopenia
  • Defer invasive procedures if referral to specialized center is planned 1

Common Etiologies to Consider

• Reduced Production

  • Bone marrow failure syndromes
  • Leukemia/lymphoma
  • Myelodysplastic syndromes
  • Megaloblastic anemia (B12, folate deficiency)
  • Viral suppression

• Increased Destruction/Utilization

  • Autoimmune disorders
  • Hypersplenism
  • Severe infection/sepsis 5, 7

• Other Causes

  • Congenital neutropenias (rare)
  • Nutritional deficiencies
  • Alcoholism
  • Radiation exposure 3

By following this systematic approach to the workup of leukopenia, clinicians can efficiently identify the underlying cause and implement appropriate management strategies to prevent complications and improve outcomes.