What is the initial workup for a patient presenting with leukopenia?

Initial Workup for Leukopenia

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

Step 1: Laboratory Studies

• Complete Blood Count (CBC) with differential 1

  • Evaluate all cell lines to determine if isolated leukopenia or pancytopenia
  • Calculate Absolute Neutrophil Count (ANC)
  • Assess severity: mild (ANC 1000-1500/μL), moderate (ANC 500-1000/μL), severe (ANC <500/μL)

• Peripheral Blood Smear Review 1

  • Manual differential count to evaluate neutrophil morphology and maturation
  • Look for morphological abnormalities, dysplasia, or presence of blast cells
  • Essential for accurate diagnosis and classification

• Additional Laboratory Tests 1

  • Complete metabolic panel
  • Lactate dehydrogenase (LDH)
  • Coagulation studies (PT, PTT, fibrinogen)
  • Infection workup as clinically indicated

Step 2: Bone Marrow Examination

If the cause is not apparent from history or initial testing, bone marrow examination is essential and should include: 2

• Bone marrow aspirate and biopsy with morphologic evaluation
• Flow cytometry analysis for immunophenotyping
• Cytogenetic analysis (conventional karyotyping)
• Molecular genetic testing as indicated

The pathologist should evaluate bone marrow aspirate smears, bone marrow trephine core biopsy, touch preparations, and/or marrow clots to determine the underlying cause 2.

Step 3: Specialized Testing Based on Clinical Suspicion

If Acute Leukemia is Suspected:

• Immunophenotyping panel should be comprehensive enough to distinguish AML, B-ALL, T-ALL, and mixed-phenotype acute leukemia 2
• Cytogenetic studies to identify recurrent chromosomal abnormalities 2
• Molecular genetic testing for specific mutations based on leukemia subtype 2

If Drug-Induced Leukopenia is Suspected:

• Thorough medication history, including review of:
  • Chemotherapeutic agents
  • Antibiotics
  • Antipsychotics
  • Colchicine (known to cause leukopenia) 3

Urgent Management Considerations

• For patients with fever (≥38.3°C) and ANC <500/μL:

  • Immediate broad-spectrum antibiotics
  • Hospital admission
  • Close monitoring for sepsis 1

• For severe leukopenia (<1000/μL):

  • Poses an acute threat to life
  • Requires immediate search for underlying cause 4

Common Pitfalls and Caveats

1. Failing to obtain manual differential count: Automated counts may miss important morphological abnormalities that are crucial for diagnosis 1, 5

2. Not checking previous blood counts: Review of previous CBCs helps establish whether leukopenia is acute or chronic, which narrows differential diagnosis 5

3. Missing pancytopenia: Always assess red blood cell and platelet counts; bi- or pancytopenia usually implies bone marrow production issues 5

4. Delaying workup in severe neutropenia: Any leukopenia <1000/μL requires urgent evaluation 4

5. Redundant testing: If patient requires referral to a specialized center, defer invasive procedures like bone marrow aspiration to avoid duplicate procedures, patient discomfort, and additional costs 2

By following this systematic approach, the underlying cause of leukopenia can be identified efficiently, allowing for appropriate management and treatment to reduce morbidity and mortality.