What is the management approach for a patient with leukocytosis?

Management of Leukocytosis (WBC 23,000)

For a patient with leukocytosis (WBC 23,000), immediate evaluation of the underlying cause should be performed, followed by targeted therapy based on the etiology, with rapid cytoreduction through hydroxyurea or leukapheresis for severe cases with symptoms of leukostasis. 1

Diagnostic Evaluation

Initial Assessment

• Complete blood count with differential to characterize the type of leukocytosis
• Peripheral blood smear to assess cell morphology and maturity
• Flow cytometry for immunophenotyping if hematologic malignancy is suspected
• Bone marrow aspiration if leukemia is suspected

Common Causes to Consider

1. Infection (most common cause of leukocytosis)

   • Bacterial infections typically cause neutrophilia with left shift
   • Viral infections often cause lymphocytosis
   • Consider C. difficile infection (present in 16% of patients with leukocytosis) 2

2. Hematologic malignancies

   • Acute leukemias (AML, ALL)
   • Chronic leukemias (CML, CLL)
   • Myeloproliferative disorders

3. Non-malignant causes

   • Stress response (surgery, trauma, seizures)
   • Medications (corticosteroids, lithium, beta-agonists)
   • Inflammatory conditions
   • Smoking, obesity
   • Asplenia

Management Algorithm

For WBC 23,000 without symptoms of leukostasis:

1. Identify and treat underlying cause:

   • For infections: Appropriate antimicrobial therapy
   • For medication-induced: Consider dose adjustment or alternative medication
   • For inflammatory conditions: Treat underlying condition

2. Monitoring:

   • Serial CBC to track WBC trends
   • Monitor for development of symptoms

For WBC >100,000 or symptoms of leukostasis (medical emergency):

1. Immediate cytoreduction 1:

   • Hydroxyurea (initial dose 50-100 mg/kg/day)
   • Consider leukapheresis for rapid reduction (can achieve 30-80% reduction within hours)

2. Specific management based on underlying cause:

   • For AML: Initiate induction chemotherapy with cytarabine plus anthracycline 3
   • For APL: Start ATRA immediately when suspected; add chemotherapy if WBC >10 × 10⁹/L 3
   • For CML: Consider tyrosine kinase inhibitors 3

Special Considerations

For Acute Promyelocytic Leukemia (APL)

• Start ATRA immediately if APL is suspected 3
• If WBC >10 × 10⁹/L, add chemotherapy without delay even if molecular results are pending 3
• Options for cytoreduction include:
  • Idarubicin (12 mg/m²)
  • Gemtuzumab ozogamicin (6-9 mg/m²)
  • Hydroxyurea (2-4 g per day) 3
• Avoid leukapheresis due to risk of fatal hemorrhage 3
• Consider prophylactic steroids (dexamethasone) to prevent differentiation syndrome 3

For Hyperleukocytosis (WBC >100,000)

• Medical emergency requiring immediate intervention due to risk of brain infarction and hemorrhage 4
• Aggressive hydration and allopurinol/rasburicase to prevent tumor lysis syndrome
• Monitor for signs of end-organ damage (CNS, pulmonary, renal)

For Unexplained Leukocytosis

• Consider persistent inflammation-immunosuppression and catabolism syndrome (PICS) 5
• Avoid prolonged empiric broad-spectrum antibiotics without clear evidence of infection
• Monitor for colonization with resistant organisms, especially C. difficile 5

Pitfalls and Caveats

1. Don't assume all leukocytosis is infection

   • Up to 47% of cases may be due to non-infectious causes 2

2. Avoid delay in treatment for suspected APL

   • Start ATRA immediately; discontinue only if diagnosis is not confirmed 3

3. Be cautious with leukapheresis

   • Contraindicated in APL due to risk of fatal hemorrhage 3
   • May cause hemodynamic instability and electrolyte abnormalities

4. Don't miss C. difficile infection

   • Present in 25% of patients with WBC >30,000 without hematologic malignancy 2
   • May occur without diarrheal symptoms

5. Recognize leukostasis as a medical emergency

   • WBC >100,000 requires immediate intervention 4
   • Symptoms include neurological deficits, respiratory distress, and priapism

By following this structured approach to leukocytosis, clinicians can efficiently identify the underlying cause and implement appropriate management strategies to improve patient outcomes.