What is the workup for leukopenia?

Comprehensive Workup for Leukopenia

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

Initial Laboratory Evaluation

Essential First-Line Tests

• Complete blood count (CBC) with differential
• Manual differential count to evaluate neutrophil morphology and maturation
• Peripheral blood smear review
• Comprehensive metabolic panel
• Lactate dehydrogenase (LDH)
• Coagulation studies (PT, PTT, fibrinogen)

Clinical Assessment

• Medication history (focus on chemotherapeutic agents, antibiotics, antipsychotics)
• Recent infections or viral illnesses
• Underlying autoimmune conditions
• Exposure history (radiation, chemicals, toxins)
• Physical examination for splenomegaly, lymphadenopathy, or signs of infection

Secondary Evaluation Based on Initial Findings

For Isolated Leukopenia

• Review previous CBCs to determine if acute or chronic
• Evaluate other cell lines (if normal, suggests peripheral destruction or redistribution)
• Consider viral studies (HIV, hepatitis, EBV, CMV)
• ANA and other autoimmune markers if clinically indicated

For Pancytopenia or Bicytopenia

• Bone marrow aspiration and biopsy with:
  • Morphologic examination
  • Flow cytometry for immunophenotyping
  • Cytogenetic analysis
  • Molecular genetic testing as indicated 2

Specialized Testing Based on Clinical Suspicion

For Suspected Autoimmune Causes

• Antineutrophil antibodies
• Rheumatologic panel (ANA, RF, anti-dsDNA)
• Complement levels

For Suspected Hematologic Malignancy

• Bone marrow examination with flow cytometry
• Cytogenetic studies
• Molecular testing for specific mutations 2

For Suspected Drug-Induced Leukopenia

• Discontinuation of suspected medication
• Monitoring of CBC for recovery after medication discontinuation 1

Management Approach

Severe Neutropenia (ANC <500/mcL)

• Immediate broad-spectrum antibiotics if febrile
• Hospital admission for close monitoring
• Consider granulocyte colony-stimulating factor (G-CSF) for specific indications 3

Moderate Neutropenia (ANC 500-1000/mcL)

• Close monitoring
• Low threshold for antibiotic therapy if signs of infection
• Identification and treatment of underlying cause

Mild Neutropenia (ANC 1000-1500/mcL)

• Regular CBC monitoring until resolution
• Treatment of underlying condition

Special Considerations

Drug-Induced Leukopenia

• Most common medications: chemotherapeutic agents, antibiotics, antipsychotics, anticonvulsants
• Management: discontinuation of suspected medication and consideration of alternatives 1

Infection-Related Leukopenia

• Treatment of underlying infection
• Regular CBC monitoring until resolution 1

Autoimmune Leukopenia

• Treatment of underlying autoimmune condition
• Consider immunosuppressive therapy in severe cases 2

Avoiding Common Pitfalls

• Verify leukopenia with repeat testing to rule out laboratory error or EDTA-induced pseudoleukopenia 4
• Avoid redundant testing if referral to specialized center is planned 1
• Consider severe leukopenia (<1000/μL) a potential medical emergency requiring immediate evaluation 5
• Don't attribute leukopenia solely to medication without excluding other causes
• Remember that leukopenia may be the first manifestation of serious underlying conditions including hematologic malignancies

Follow-up and Monitoring

• Frequency of CBC monitoring depends on severity and underlying cause
• Consider hematology consultation for persistent unexplained leukopenia 1
• For patients with chronic benign leukopenia, establish a baseline and monitor periodically

Remember that any leukopenia below 1000/μL poses a potential threat to life and mandates an immediate search for the underlying cause, with bone marrow examination often being necessary for definitive diagnosis 5.