What is the workup for neutrophilia (elevated neutrophil count)?

Workup for Neutrophilia

The diagnostic workup for neutrophilia should include a thorough history focusing on medications, exposures, infections, and symptoms of underlying disorders, followed by laboratory evaluation with CBC with differential, blood smear, inflammatory markers, and bone marrow examination if necessary. 1

Initial Assessment

History and Physical Examination

• Medication history (particularly corticosteroids, lithium, colony-stimulating factors)
• Recent infections or inflammatory conditions
• Smoking status
• Symptoms of underlying malignancy
• Family history of hematologic disorders
• Physical examination focusing on:
  • Signs of infection
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Skin lesions

First-line Laboratory Tests

• Complete blood count (CBC) with differential
• Peripheral blood smear examination 2
• Inflammatory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) 2
• Serum creatinine
• Liver function tests

Secondary Evaluation

Infectious Workup

• Bacterial cultures if infection suspected
• Viral studies (particularly CMV, EBV, HIV) 2
• Evaluation for fungal infections if clinically indicated

Inflammatory/Autoimmune Workup

• Serum amyloid A (SAA) and S100 proteins (if available) 2
• Autoimmune markers if clinically indicated

Bone Marrow Evaluation

• Bone marrow aspiration and biopsy when myeloid neoplasm suspected 2, 3
• Cytogenetic analysis to exclude clonal disorders 2
• Molecular testing for specific mutations (e.g., JAK2, CALR, MPL, BCR-ABL) 3

Specialized Testing Based on Clinical Suspicion

For Suspected Myeloproliferative Neoplasms

• BCR-ABL testing to exclude chronic myeloid leukemia 3
• JAK2, CALR, and MPL mutation analysis 3
• CSF3R mutation analysis (for chronic neutrophilic leukemia) 3

For Suspected Chronic Myelomonocytic Leukemia

• Molecular assays to exclude bcr/abl fusion gene
• Rearrangement of PDGFRA and PDGFRB 2

Interpretation and Next Steps

Reactive Causes of Neutrophilia

• Infection (bacterial, viral, fungal)
• Inflammation (autoimmune disorders, tissue damage)
• Medications (corticosteroids, lithium)
• Physiologic stress (surgery, exercise, pregnancy)
• Smoking

Clonal/Neoplastic Causes

• Chronic myeloid leukemia (BCR-ABL positive)
• Chronic neutrophilic leukemia
• Polycythemia vera
• Essential thrombocythemia
• Primary myelofibrosis
• Atypical chronic myeloid leukemia
• Chronic myelomonocytic leukemia

Common Pitfalls to Avoid

1. Failure to exclude reactive causes before pursuing extensive workup for primary hematologic disorders
2. Overlooking medication-induced neutrophilia (particularly corticosteroids)
3. Missing subtle signs of infection in patients with neutrophilia
4. Not considering smoking as a common cause of mild neutrophilia
5. Inadequate follow-up of persistent unexplained neutrophilia

Clinical Decision Algorithm

1. Confirm neutrophilia (absolute neutrophil count >7500/μL)
2. Evaluate for obvious reactive causes (infection, inflammation, medications)
3. If reactive cause identified, treat underlying condition and monitor neutrophil count
4. If no reactive cause identified or neutrophilia persists despite treatment:
   • Perform peripheral blood smear examination
   • Consider bone marrow examination with cytogenetics
   • Perform molecular testing based on clinical suspicion
5. Refer to hematology if primary hematologic disorder suspected or neutrophilia remains unexplained

Remember that persistent unexplained neutrophilia, especially when severe or accompanied by other hematologic abnormalities, warrants thorough investigation to exclude myeloproliferative neoplasms and other clonal disorders 3.