From the Guidelines
The initial workup for an elevated white blood cell count should begin with a complete blood count with differential to characterize the specific cell types involved, as recommended by the Infectious Diseases Society of America in 2009 1. This approach is crucial for identifying the underlying cause of the elevated WBC count, which could range from bacterial infections to hematologic malignancies. A thorough history and physical examination are also essential to identify potential causes such as infection, inflammation, stress, medication effects, or hematologic disorders. Additional first-line tests may include:
- Basic metabolic panel
- Liver function tests
- Urinalysis
- Blood cultures if infection is suspected Specific testing should be guided by clinical presentation, such as:
- Chest X-ray for respiratory symptoms
- Inflammatory markers (ESR, CRP) for suspected inflammatory conditions
- Peripheral blood smear if leukemia is a concern The differential diagnosis for leukocytosis is broad, including bacterial infections, tissue damage, inflammatory conditions, medications, hematologic malignancies, and physiologic stress, as noted in a study published in 2000 1. The pattern of elevation provides important diagnostic clues, with neutrophilia typically suggesting bacterial infection or inflammation, lymphocytosis indicating viral infection or lymphoproliferative disorders, monocytosis occurring with chronic infections or malignancies, and eosinophilia pointing to allergic reactions or parasitic infections. For very high WBC counts (>30,000/μL) without obvious cause, hematology consultation should be considered to evaluate for potential hematologic malignancies, as suggested by the clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America 1.
From the Research
Initial Workup for Elevated White Blood Cell Count
The initial workup for an elevated white blood cell (WBC) count involves a thorough history, physical examination, and peripheral blood smear 2, 3.
- A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 2.
- The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses 2.
- Infections and chronic inflammatory conditions are common causes of secondary leukocytosis, and a high WBC and granulocyte count can be clear evidence of the bacterial aetiology of respiratory infection 2, 4.
- However, low or normal WBC values do not rule out bacterial infection, and C-reactive protein (CRP) levels can be a better indicator of infection in some cases 5.
Differential Diagnosis
The differential diagnosis of leukocytosis can be broadly divided into primary malignant diseases and secondary causes that are expected physiologic responses of the bone marrow 3.
- Primary malignant diseases include acute and chronic leukemias, which can present with symptoms such as fever, weight loss, bruising, or fatigue 2, 3.
- Secondary causes of leukocytosis include infections, chronic inflammatory conditions, certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions 2.
- Stressors capable of causing an acute leukocytosis include surgery, exercise, trauma, and emotional stress 2.
Referral to a Hematologist/Oncologist
Referral to a hematologist/oncologist is indicated in cases of suspected acute leukemia or if malignancy cannot be excluded 2, 3.