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

Initial Assessment

Laboratory Studies

• Complete blood count (CBC) with differential to confirm leukopenia and identify which white blood cell lines are affected 1
• Peripheral blood smear evaluation to assess morphology of remaining white blood cells and identify potential dysplastic changes 1
• Comprehensive metabolic panel to evaluate for underlying systemic conditions 2

Clinical Assessment

• Detailed medical history focusing on:
  • Duration of leukopenia and previous blood counts 1
  • Medication history (drug-induced leukopenia is common) 3
  • Recent infections 1
  • Exposure to toxins or radiation 1
  • Family history of hematologic disorders 1
• Physical examination with attention to:
  • Signs of infection 3
  • Lymphadenopathy 1
  • Hepatosplenomegaly (may indicate hypersplenism) 1, 3

Secondary Evaluation Based on Initial Findings

If Isolated Leukopenia

• Review medication list for potential causative agents 3
• Evaluate for recent viral infections 4
• Consider autoimmune markers if autoimmune etiology is suspected 1
• Vitamin B12 and folate levels if megaloblastic anemia is suspected 1

If Pancytopenia or Bicytopenia is Present

• Bone marrow aspiration and biopsy is essential for evaluating bone marrow production and identifying underlying hematologic malignancies 2
• Flow cytometry for immunophenotyping to diagnose potential hematologic malignancies 2
• Cytogenetic studies, including conventional karyotyping, to identify chromosomal abnormalities 2
• Molecular studies (PCR or next-generation sequencing) to detect specific genetic mutations 2

If Acute Leukemia is Suspected

• Bone marrow aspirate for morphologic evaluation 5
• Bone marrow trephine core biopsy 5
• Flow cytometry immunophenotyping 1
• Cytogenetic analysis (karyotype) 1
• Molecular genetic testing 1

Management of Febrile Neutropenia

• Immediate assessment for patients with fever and neutropenia (ANC <1,500/mcL) 4
• Urgent administration of broad-spectrum antibiotics for patients with fever and severe neutropenia (ANC <500/mcL) to reduce mortality 6
• Hospital admission for patients with agranulocytosis and fever 6

Common Etiologies of Leukopenia

• Decreased production due to:
  • Bone marrow failure (aplastic anemia, leukemia) 1
  • Medications (chemotherapy, antibiotics, anticonvulsants) 3
  • Nutritional deficiencies (B12, folate) 1
• Increased destruction or utilization:
  • Infections (viral, bacterial, parasitic) 3, 4
  • Hypersplenism 3
  • Autoimmune disorders 1
• Redistribution:
  • Severe infections 4
  • Inflammatory conditions 7

Pitfalls and Caveats

• Always check previous blood counts to determine if leukopenia is acute or chronic 6
• Do not delay antibiotic therapy in febrile neutropenia while waiting for diagnostic results 6
• Consider bone marrow examination when leukopenia is persistent or associated with other cytopenias 2
• Remember that leukopenia may be the first sign of a serious underlying condition, including hematologic malignancies 7, 8