What is the appropriate work-up for Leukocytosis (elevated White Blood Cell count)?

From the Guidelines

The initial workup for leukocytosis should include a complete blood count with differential, peripheral blood smear, and basic metabolic panel, as recommended by the most recent guidelines 1. First, determine if the elevated white blood cell count represents a reactive process or a primary hematologic disorder. For reactive leukocytosis, identify and treat the underlying cause such as infection, inflammation, stress, or medication effect. Common medications that cause leukocytosis include corticosteroids, lithium, and colony-stimulating factors. If infection is suspected, obtain appropriate cultures and consider empiric antibiotics based on the likely source. For significant unexplained leukocytosis (WBC >30,000/μL) or abnormal cell morphology on peripheral smear, consult hematology as this may indicate a hematologic malignancy. Additional testing may include flow cytometry, bone marrow biopsy, and cytogenetic studies if a hematologic disorder is suspected. The pattern of cell elevation provides important diagnostic clues - neutrophilia typically suggests bacterial infection or inflammation, lymphocytosis may indicate viral infection or lymphoproliferative disorders, eosinophilia suggests allergic or parasitic conditions, and monocytosis can occur with chronic infections or certain malignancies. Serial CBC monitoring is important to track response to treatment and disease progression.

Some key points to consider in the workup of leukocytosis include:

• History and physical examination to identify underlying causes such as infection, inflammation, or medication effect 1
• CBC with differential and reticulocyte count to evaluate the type and severity of leukocytosis 1
• Peripheral blood smear to evaluate cell morphology and identify any abnormal cells 1
• Basic metabolic panel to evaluate for any underlying metabolic disorders that may be contributing to the leukocytosis 1
• Consideration of bone marrow biopsy and cytogenetic studies if a hematologic disorder is suspected 1
• Evaluation for infectious causes, such as bacterial, viral, or fungal infections 1
• Consideration of tumor lysis syndrome and other complications of hyperleukocytosis 1

It is essential to prioritize the most recent and highest quality study, which in this case is the 2021 guideline update from the Journal of Clinical Oncology 1. This guideline provides recommendations for the diagnostic workup and management of immune-related adverse events, including leukocytosis. By following these recommendations, clinicians can ensure that patients with leukocytosis receive prompt and effective treatment, which can improve outcomes and reduce morbidity and mortality.

From the Research

Leukocytosis Work-up

• Leukocytosis is a common laboratory finding that can be caused by various conditions, including infections, inflammatory processes, and primary bone marrow disorders 2.
• The differential diagnosis of leukocytosis includes physiologic responses to infectious and inflammatory processes, as well as primary hematologic disorders such as leukemias, lymphomas, and myeloproliferative neoplasms 3.
• Effective evaluation of leukocytosis requires a thorough history, physical examination, and review of laboratory tests, including complete blood count and peripheral blood smear 3.

Clinical Features and Outcome

• Patients with unexplained or persistent leukocytosis may appear to be in a state of continued inflammation, described as the persistent inflammation-immunosuppression and catabolism syndrome (PICS) 4.
• These patients often have a prolonged hospital course, extensive use of empiric broad-spectrum antibiotics, and may become colonized with resistant opportunistic organisms 4.
• The most common causes of admission in patients with leukocytosis include sepsis, major trauma, cerebrovascular accident, and major elective surgery 4.

Diagnostic Approach

• The diagnostic approach to leukocytosis should include a repeat complete blood count with peripheral smear, which may provide helpful information on the types and maturity of white blood cells 5.
• The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or lymphocytosis in childhood viral illnesses 5.
• Symptoms suggestive of a hematologic malignancy, such as fever, weight loss, bruising, or fatigue, should prompt referral to a hematologist/oncologist 5.

Interpretation of Blood Cell Count

• Physiologic leucocyte count is in the range of 4-10 × 10^9 per liter of blood, and abnormal values may be caused by various benign or malignant conditions 6.
• Changes in leukocytes counts can be caused by primary hematologic disorders or secondary/reactive states, and it is essential to interpret changes in blood cell count correctly and choose an adequate approach in the investigation process 6.