Appropriate Workup for Leukopenia
The appropriate workup for leukopenia should begin with a complete blood count (CBC) with differential, peripheral blood smear review, and comprehensive metabolic panel, followed by targeted testing based on clinical presentation to identify the underlying cause. 1, 2
Initial Evaluation
Complete Blood Count (CBC) with differential: Essential first step to confirm leukopenia and identify which white blood cell populations are affected (neutrophils, lymphocytes, etc.) 2
Peripheral blood smear review: Critical for morphological assessment of white blood cells and to identify abnormalities in other cell lines 2
Review of previous blood counts: Important to determine if leukopenia is acute or chronic, and to establish the pattern and progression 1
Assessment of other cell lines: Determine if isolated leukopenia or if accompanied by anemia and/or thrombocytopenia (suggesting bone marrow involvement) 2
Comprehensive metabolic panel: To evaluate for underlying systemic conditions and to monitor for tumor lysis syndrome 3
Secondary Evaluation Based on Initial Findings
If isolated neutropenia is identified:
Medication review: Assess for drug-induced neutropenia, which is a common cause 4
Infectious disease workup: Consider viral studies (HIV, hepatitis, EBV, CMV) as infections can cause leukopenia 4
Autoimmune screening: ANA, rheumatoid factor, and other autoimmune markers if clinically indicated 5
Vitamin B12 and folate levels: To rule out megaloblastic anemia as a cause 4
If pancytopenia or bicytopenia is present:
Bone marrow aspiration and biopsy: Essential for evaluating bone marrow production and identifying underlying hematologic malignancies 3
Flow cytometry: For immunophenotyping to diagnose potential hematologic malignancies 3
Cytogenetic studies: Conventional karyotyping to identify chromosomal abnormalities 3
Molecular studies: PCR or next-generation sequencing for specific genetic mutations 3
Special Considerations
Febrile neutropenia: If patient presents with fever and severe neutropenia (ANC <500/μL), immediate hospitalization and broad-spectrum antibiotics are required 1
Severe chronic neutropenia: Consider testing for congenital neutropenia syndromes, especially in pediatric patients 4
Splenomegaly: Abdominal imaging to evaluate for hypersplenism if clinically suspected 4
Management Considerations
For drug-induced leukopenia: Consider discontinuation of suspected medication and monitoring for recovery 4
For severe neutropenia: Consider granulocyte colony-stimulating factors (G-CSF) such as filgrastim at 5 mcg/kg/day subcutaneously for idiopathic neutropenia 6
For infectious causes: Targeted antimicrobial therapy based on identified pathogen 4
Common Pitfalls to Avoid
Overlooking medication causes: Many medications can cause leukopenia; always perform a thorough medication review 4
Focusing only on white blood cells: Always evaluate all cell lines (red blood cells, platelets) as pancytopenia suggests different etiologies than isolated leukopenia 2
Delaying workup in severe neutropenia: Patients with ANC <500/μL are at high risk for life-threatening infections and require urgent evaluation 1
Missing bone marrow evaluation: When leukopenia is persistent or associated with other cytopenias, bone marrow examination is crucial 3