What is the initial workup for a patient presenting with leukopenia (low white blood cell count)?

Initial Workup for Leukopenia

The initial workup for a patient presenting with leukopenia should include a complete blood count with differential, peripheral blood smear evaluation, and a thorough clinical assessment to determine the underlying cause. 1

Definition and Clinical Significance

• Leukopenia is defined as an abnormal reduction in circulating white blood cells, with neutropenia (absolute neutrophil count <1,500/mcL) being the most common cause 2, 3
• The major danger of leukopenia, particularly neutropenia, is the increased risk of infection, which can be life-threatening 2

Initial Assessment

Laboratory Studies

• Complete blood count (CBC) with differential and platelet count to determine:
  • Severity of leukopenia
  • Whether other cell lines are affected (bicytopenia or pancytopenia suggests bone marrow dysfunction) 4
  • Absolute neutrophil count (ANC) to assess neutropenia severity 3
• Peripheral blood smear evaluation is essential to:
  • Confirm the leukopenia
  • Assess morphology of remaining white blood cells
  • Identify potential dysplastic changes 4, 1

Clinical Assessment

• Thorough medical history focusing on:
  • Duration of leukopenia (acute vs. chronic)
  • Previous blood counts to establish pattern (new onset vs. longstanding) 4
  • Medication history, particularly drugs associated with leukopenia 5
  • History of hematologic disorders or predisposing conditions 1
  • Recent infections, exposure to toxins, or radiation 1
  • Family history of hematologic disorders 1
• Physical examination with attention to:
  • Signs of infection
  • Lymphadenopathy
  • Hepatosplenomegaly 1

Further Diagnostic Workup

For Suspected Acute Leukemia

If acute leukemia is suspected based on clinical presentation and initial blood work:

• Bone marrow aspirate and biopsy for:
  • Morphologic evaluation
  • Flow cytometry
  • Cytogenetic analysis
  • Molecular genetic testing 1
• Additional studies may include:
  • Conventional cytogenetic analysis (karyotype)
  • Fluorescence in situ hybridization (FISH)
  • Molecular genetic testing 1

For Other Etiologies

• Targeted testing based on suspected etiology:
  • Infectious disease workup (viral studies, blood cultures)
  • Autoimmune markers
  • Vitamin B12 and folate levels (for megaloblastic anemia)
  • Spleen imaging if hypersplenism is suspected 2, 6

Management Considerations

• For febrile neutropenia (fever with ANC <500/mcL or <1,000/mcL with predicted decline to <500/mcL):
  • Immediate hospital admission
  • Prompt initiation of broad-spectrum antibiotics 4, 3
• For non-febrile patients:
  • Management directed at underlying cause
  • Close monitoring of blood counts
  • Infection prevention strategies 3

Common Etiologies of Leukopenia

• Decreased production:
  • Bone marrow failure (aplastic anemia, leukemia)
  • Nutritional deficiencies (B12, folate)
  • Medications (chemotherapy, certain antibiotics, anticonvulsants)
  • Viral infections (HIV, hepatitis) 2, 6
• Increased destruction:
  • Hypersplenism
  • Autoimmune disorders
  • Overwhelming infection 2
• Redistribution:
  • Severe infection
  • Stress response 6

Pitfalls and Caveats

• Don't assume all leukopenia is pathological; some ethnic groups have lower normal ranges 6
• Always review previous CBCs to determine if the leukopenia is new or chronic 4
• Consider medication-induced leukopenia, which may resolve with discontinuation of the offending agent 5
• Don't delay antibiotic therapy in febrile neutropenia while waiting for diagnostic results 4