What are the next steps for a patient with leukocytosis?

Evaluation and Management of Leukocytosis (WBC 16)

A white blood cell count of 16,000/μL requires a systematic diagnostic approach to identify the underlying cause, with priority given to ruling out serious infections, hematologic malignancies, and other conditions that may impact mortality and morbidity.

Initial Assessment

• Leukocytosis (WBC >11,000/μL) has many potential etiologies, including both benign and malignant causes 1
• The first step is to review the complete blood count with differential to identify which cell lines are elevated and assess for abnormalities in other cell lines 2
• The presence of immature forms ("left shift") suggests an inflammatory or infectious process 2

Common Non-Malignant Causes

Infections

• Bacterial infections are the most common cause of neutrophilic leukocytosis and should be the first consideration 1
• Viral infections, particularly in children, often present with lymphocytosis rather than neutrophilia 1
• Parasitic infections may present with eosinophilia 1

Physiologic and Medication-Related Causes

• Physical stress (surgery, trauma, seizures), emotional stress, and exercise can cause transient leukocytosis 2
• Medications commonly associated with leukocytosis include corticosteroids, lithium, and beta-agonists 2
• Smoking, obesity, and chronic inflammatory conditions can cause persistent mild leukocytosis 1

Other Non-Malignant Causes

• Tissue damage without active infection can drive persistent leukocytosis, as seen in the persistent inflammation-immunosuppression and catabolism syndrome (PICS) 3
• Asplenia can result in persistent leukocytosis due to decreased clearance of white blood cells 1

Concerning Features Suggesting Malignancy

• Extremely elevated white blood cell counts (particularly >100,000/μL, which represents a medical emergency) 2
• Concurrent abnormalities in red blood cell or platelet counts 2
• Constitutional symptoms: fever, weight loss, night sweats, fatigue 1
• Physical findings: hepatomegaly, splenomegaly, lymphadenopathy 2
• Unexplained bruising or bleeding 2

Diagnostic Approach

• Repeat complete blood count with peripheral smear examination to assess cell morphology and maturity 1
• Review medication list and recent stressors that could explain leukocytosis 2
• Conduct focused physical examination looking for sources of infection or signs of hematologic malignancy 1
• Consider bone marrow examination if hematologic malignancy is suspected, especially with abnormalities in other cell lines 4

Specific Conditions to Consider

Acute Myeloid Leukemia (AML)

• Patients with excessive leukocytosis at presentation may require emergency leukapheresis prior to induction chemotherapy 4
• Cytogenetic analysis is crucial for risk stratification, with t(15;17), t(8;21), and t(16;16) considered favorable 4
• Induction chemotherapy should include an anthracycline and cytosine arabinoside 4

Acute Promyelocytic Leukemia (APL)

• Represents a medical emergency due to risk of fatal hemorrhage 4
• Treatment with all-trans retinoic acid (ATRA) should be started immediately if APL is suspected 4
• Coagulopathy management is critical, maintaining fibrinogen above 100-150 mg/dL and platelets above 30-50 × 10^9/L 4

Chronic Myelogenous Leukemia (CML)

• Symptomatic leukocytosis in CML may be treated with hydroxyurea, apheresis, or tyrosine kinase inhibitors 4
• Risk stratification using Sokal or Hasford scoring systems guides treatment approach 4

When to Refer to Hematology/Oncology

• WBC count >30,000/μL without obvious explanation 1
• Abnormalities in multiple cell lines 2
• Persistent unexplained leukocytosis despite treatment of apparent cause 3
• Presence of immature or abnormal cells on peripheral smear 2
• Constitutional symptoms suggesting underlying malignancy 1

Important Caveats

• An isolated elevated WBC is not sufficient to diagnose specific conditions like Clostridium difficile infection 5
• Persistent unexplained leukocytosis in hospitalized patients is often associated with prolonged hospital stays and may represent PICS rather than occult infection 3
• WBC counts above 100,000/μL represent a medical emergency due to risk of brain infarction and hemorrhage 2
• Avoid unnecessary prolonged courses of broad-spectrum antibiotics in patients with persistent leukocytosis without clear evidence of infection 3