What is the initial step in the workup of a patient with leukopenia (low white blood cell count)?

Initial Workup for Leukopenia

The initial step in the workup of a patient with leukopenia should include a complete blood count (CBC) with differential and peripheral blood smear evaluation. 1

Initial Assessment

Laboratory Studies

• Complete blood count (CBC) with differential is essential to confirm leukopenia and assess all cell lines 1
• Peripheral blood smear evaluation is critical to:
  • Confirm the leukopenia 1
  • Assess morphology of remaining white blood cells 1
  • Identify potential dysplastic changes 1, 2
  • Examine for leukemic blasts or other abnormal cells 3

Clinical Assessment

• Thorough medical history focusing on:
  • Duration of leukopenia and previous blood counts 2
  • Medication history (drug-induced leukopenia is common) 4
  • History of hematologic disorders 1
  • Recent infections 4
  • Exposure to toxins or radiation 1
  • Family history of hematologic disorders 1
• Physical examination with attention to:
  • Signs of infection 1
  • Lymphadenopathy 1
  • Hepatosplenomegaly (suggesting hypersplenism) 1, 4

Categorization by Severity and Duration

• Mild leukopenia (WBC 3,000-4,000/mm³): Lower risk, may require monitoring 5
• Moderate leukopenia (WBC 2,000-3,000/mm³): Increased infection risk 5
• Severe leukopenia/agranulocytosis (ANC <500/mm³): Medical emergency requiring immediate intervention 2
• Transient vs. chronic: Check previous blood counts to determine if this is new or longstanding 2

Common Etiologies to Consider

• Decreased production due to:
  • Bone marrow failure (aplastic anemia, leukemia) 1
  • Megaloblastic anemia (B12/folate deficiency) 4
  • Drug-induced suppression 4
• Increased destruction or utilization:
  • Infections (viral, bacterial) 4
  • Hypersplenism 4
  • Autoimmune disorders 1
• Genetic/hereditary causes:
  • Primary neutropenia (rare, especially in children) 4
  • Familial Mediterranean fever (consider if episodic leukopenia) 6

Management Algorithm

1. First step: Obtain CBC with differential and peripheral blood smear 1, 2
2. If severe neutropenia (ANC <500/mm³) with fever:
   • Immediate hospital admission 2
   • Broad-spectrum antibiotics 2
   • Blood cultures 5
3. If abnormal peripheral smear with blasts or dysplastic changes:
   • Bone marrow aspirate and biopsy for morphologic evaluation 3
   • Flow cytometry, cytogenetic analysis, and molecular genetic testing 3
4. If mild to moderate leukopenia without concerning features:
   • Review medication list and discontinue potential offending agents 4
   • Check vitamin B12 and folate levels 1
   • Consider autoimmune markers if clinically indicated 1
   • Spleen imaging if hypersplenism is suspected 1

Special Considerations

• For suspected acute leukemia, comprehensive bone marrow evaluation is essential, including:
  • Bone marrow aspirate and biopsy 3
  • Flow cytometry immunophenotyping 3
  • Cytogenetic analysis 3
  • Molecular genetic testing 3
• For suspected chronic neutropenia, confirm diagnosis by evaluating serial CBCs with differential and platelet counts, and evaluating bone marrow morphology and karyotype 7
• In patients with febrile neutropenia, risk assessment should be performed systematically to determine appropriate management 5

Pitfalls to Avoid

• Failing to review previous CBCs to determine if leukopenia is new or chronic 2
• Overlooking medication-induced causes, which are common and potentially reversible 4
• Delaying treatment in patients with severe neutropenia and fever, which can be life-threatening 2
• Using filgrastim (G-CSF) before confirming diagnosis in suspected chronic neutropenia, which may impair diagnostic efforts 7
• Focusing only on white blood cell count without examining other cell lines that might indicate broader bone marrow dysfunction 2