What is the workup for elevated White Blood Cells (WBCs), specifically neutrophilia and lymphocytosis?

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From the Guidelines

A high white blood cell count with elevated neutrophils and lymphocytes should be initially evaluated with a complete blood count (CBC) with differential, peripheral blood smear, and reticulocyte count, as recommended by the American Society of Clinical Oncology (ASCO) guideline 1. The workup for high white blood cells, neutrophils, and lymphocytes involves a step-by-step approach to determine the underlying cause.

  • Initial evaluation:
    • CBC with differential to assess the degree of elevation and identify any abnormalities in other blood cell lines
    • Peripheral blood smear to evaluate the morphology of the white blood cells and detect any abnormal cells
    • Reticulocyte count to assess bone marrow function and response to anemia
  • Further investigation:
    • If abnormalities are detected and further investigation is necessary for a diagnosis, proceed with bone marrow evaluation, as recommended by the ASCO guideline 1
    • For neutrophilia, assess for infection (blood cultures, urinalysis, chest X-ray), inflammation, or stress response
    • For lymphocytosis, consider viral infections (EBV, CMV, HIV testing), chronic bacterial infections, or lymphoproliferative disorders
  • Additional testing:
    • Flow cytometry, cytogenetics, or molecular studies if a hematologic malignancy is suspected
    • Imaging studies (e.g., chest X-ray, abdominal CT) if infection or inflammation is suspected The timing and urgency of the workup depend on the degree of elevation and associated symptoms.
  • Mild elevations with minimal symptoms may be monitored, while marked elevations or concerning symptoms warrant urgent evaluation, as suggested by the Infectious Diseases Society of America (IDSA) guideline 1 This approach helps distinguish between reactive causes (infections, inflammation) and primary hematologic disorders that require specialized treatment.
  • It is essential to consider the clinical presentation and medical history of the patient when interpreting the results of the workup and guiding further management.

From the Research

High White Blood Cell Count

A high white blood cell count can be an indication of an underlying infection or inflammatory condition. The two main types of white blood cells that are often elevated in such cases are:

  • Neutrophils: These cells are a type of granulocyte that plays a key role in fighting bacterial infections and inflammation.
  • Lymphocytes: These cells are a type of agranulocyte that helps to fight viral infections and plays a key role in the immune system.

Workup and Diagnosis

The workup for a high white blood cell count typically involves a complete blood count (CBC) and a blood smear examination 2. The blood smear examination serves to:

  • Verify the flagged automated hematology results
  • Determine if a manual differential leukocyte count needs to be performed
  • Provide a complete hematologic picture of the case from the morphologic standpoint
  • Ensure that no clinically significant finding is missed, besides providing diagnosis or diagnostic clue(s)

Blood Smear Examination

A blood smear examination is a crucial step in the diagnosis of a high white blood cell count. It involves a microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional 2. This examination can help to:

  • Identify any abnormalities in the white blood cells, such as an increase in neutrophils or lymphocytes
  • Provide a diagnosis or diagnostic clue(s) for underlying conditions, particularly if interpreted by a physician.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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