From the Guidelines
The workup for leukocytosis without clear evidence of infection should begin with a thorough history and physical examination, followed by targeted laboratory testing, as recommended by the American Society of Clinical Oncology clinical practice guideline 1. The initial step in the workup should include:
- A comprehensive history and physical examination to identify potential causes of leukocytosis, such as lymphocyte-depleting therapy, autoimmune disease, or family history of autoimmune disease 1
- Evaluation of nutritional state as a potential cause of leukocytosis
- Assessment of spleen size
- CBC with differential and reticulocyte counts to characterize the type of elevated cells
- CXR to evaluate for presence of thymoma
- Bacterial cultures and evaluation for infection, including fungal, viral, and bacterial infections, specifically CMV/HIV 1
Additional tests should be considered based on clinical suspicion, including:
- Inflammatory markers like C-reactive protein and erythrocyte sedimentation rate
- Bone marrow examination, flow cytometry, or molecular studies to evaluate for hematologic malignancies like leukemia or lymphoma
- Autoimmune disorders through ANA, RF, and other autoimmune panels
- Medication review to identify potential causes of leukocytosis, such as corticosteroids, lithium, or colony-stimulating factors
- Specialized imaging like CT scans or PET scans to identify occult malignancy or inflammation, as recommended by the American Society of Clinical Oncology clinical practice guideline 1
A systematic approach to the workup of leukocytosis without clear evidence of infection is essential to identify the underlying cause and allow for appropriate management of the primary condition 1.
From the Research
Workup for Leukocytosis
The workup for leukocytosis (elevated White Blood Cell (WBC) count) without clear evidence of infection involves several steps:
- Repeat complete blood count (CBC) with peripheral smear to provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 2
- Leukocyte differential to show eosinophilia in parasitic or allergic conditions, or lymphocytosis in childhood viral illnesses 2
- Evaluation of symptoms suggestive of a hematologic malignancy, such as fever, weight loss, bruising, or fatigue 2
- Consideration of nonmalignant etiologies of leukocytosis, including certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions 2
Laboratory Tests
Laboratory tests that may be used in the workup of leukocytosis include:
- White blood cell count (WBC) to distinguish between bacterial and viral infections 3
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level to predict the likelihood of infection 4
- Flow cytometry, such as Leukoflow, to provide additional information on blasts, myeloid precursors, and lymphocyte subsets 5
Clinical Value of Laboratory Tests
The clinical value of laboratory tests in the workup of leukocytosis is limited:
- An elevated total WBC count has poor sensitivity and specificity for diagnosing appendicitis 6
- A temperature greater than 99.0 degrees F has minimal statistical association with the presence of appendicitis 6
- The areas under the curve for the receiver-operating characteristic (ROC) curve for an elevated total WBC count and an elevated temperature are low, indicating limited clinical utility 6