What additional labs should be ordered for a patient with leukopenia (low white blood cell count)?

Laboratory Evaluation for Low White Blood Cell Count

When evaluating a patient with leukopenia (low white blood cell count), a comprehensive laboratory workup should include complete blood count with differential, bone marrow examination, cytogenetic analysis, molecular studies, and specific tests to identify the underlying cause.

Initial Laboratory Evaluation

Essential First-line Tests

• Complete blood count (CBC) with platelets and differential 1

  • Assess all cell lines to determine if isolated leukopenia or part of bi/pancytopenia
  • Evaluate white cell differential to identify which specific cell lines are affected
  • Review peripheral blood smear for morphologic abnormalities

• Chemistry profile 1

  • Comprehensive metabolic panel including liver and renal function
  • Lactate dehydrogenase (LDH) - elevated in malignancies and hemolysis
  • Uric acid - may be elevated in high cell turnover states

• Coagulation studies 1

  • Prothrombin time (PT)
  • Partial thromboplastin time (PTT)
  • Fibrinogen

Second-line Tests Based on Clinical Suspicion

• Bone marrow examination 1

  • Bone marrow aspirate and biopsy with immunohistochemistry
  • Essential for evaluating production defects
  • Particularly important if other cytopenias are present or malignancy is suspected

• Cytogenetic and molecular studies 1

  • Conventional cytogenetics (karyotype)
  • Fluorescence in situ hybridization (FISH)
  • Molecular genetic testing for specific mutations (e.g., FLT3-ITD, NPM1, CEBPA)

Specialized Testing Based on Suspected Etiology

For Suspected Hematologic Malignancy

• Immunophenotyping 1

  • Flow cytometry of peripheral blood and/or bone marrow
  • Essential for classifying leukemias and lymphomas

• Molecular panels 1

  • Next-generation sequencing for myeloid or lymphoid mutations
  • PCR for specific gene rearrangements

For Suspected Autoimmune Etiology

• Autoimmune workup 1
  • Antinuclear antibodies (ANA)
  • Rheumatoid factor
  • Coombs test (particularly in patients with CLL, NHL, or history of autoimmune disease)

For Suspected Infectious Causes

• Infectious disease testing 2, 3
  • Blood cultures if febrile
  • Viral studies (HIV, EBV, CMV, parvovirus B19)
  • Tuberculosis testing if clinically indicated

For Suspected Nutritional Deficiencies

• Nutritional assessment 1, 4
  • Vitamin B12 and folate levels
  • Iron studies (serum iron, ferritin, total iron binding capacity)

Additional Considerations

For Suspected Drug-Induced Leukopenia

• Medication review 5, 3
  • Detailed medication history including prescription, OTC, and herbal supplements
  • Consider drug levels for medications known to cause leukopenia

For Suspected Splenic Sequestration

• Imaging studies 4
  • Abdominal ultrasound or CT scan to evaluate spleen size

Follow-up Testing

• Serial CBCs 2, 3

  • Monitor trends in white cell count
  • Particularly important in neutropenic patients to guide management

• Repeat bone marrow examination 1

  • Consider if initial evaluation is inconclusive or if clinical status changes

Common Pitfalls to Avoid

1. Failing to check previous CBCs 3

   • Historical values provide crucial context for interpreting current leukopenia

2. Overlooking pseudoleukopenia 6

   • EDTA-induced leukocyte agglutination can cause falsely low counts
   • Consider repeating CBC with citrate tube if suspected

3. Missing concomitant cytopenias 4, 3

   • Always evaluate all cell lines as pancytopenia suggests different etiologies than isolated leukopenia

4. Delaying evaluation in severe neutropenia with fever 3

   • Immediate broad-spectrum antibiotics are required in febrile neutropenia

5. Incomplete bone marrow evaluation 1

   • Ensure both aspirate and biopsy are obtained with appropriate cytogenetic and molecular studies

By following this comprehensive approach to laboratory evaluation, clinicians can efficiently identify the underlying cause of leukopenia and implement appropriate management strategies to address both the hematologic abnormality and its etiology.