Does Clozaril (clozapine) cause leukocytosis (elevated white blood cell count)?

Effect of Clozaril (Clozapine) on White Blood Cell Count

Yes, Clozaril (clozapine) can cause leukocytosis (elevated white blood cell count), though it is more commonly associated with potentially fatal agranulocytosis. 1

Primary Hematological Effects of Clozapine

• Clozapine is primarily known for causing agranulocytosis, a severe form of neutropenia with absolute neutrophil count (ANC) less than 500/μL, which occurs in approximately 1% of patients and can be fatal 2
• However, some patients receiving clozapine treatment may experience elevations in their total white blood cell count (leukocytosis), which can sometimes be persistent 1
• Interestingly, researchers have observed that white blood cell counts sometimes spike upward before agranulocytosis occurs, with one study finding that WBC spikes at least 15% above previous measurements significantly predicted development of agranulocytosis (risk ratio 3.02) 3

Monitoring Requirements for Clozapine

• Due to the risk of agranulocytosis, clozapine requires mandatory and rigorous WBC monitoring throughout treatment 2
• Before starting therapy, baseline WBC must be at least 3,500/mm³, with no evidence of myeloproliferative disorder or history of agranulocytosis 2
• The monitoring schedule includes:
  • Weekly blood cell counts for the first 6 months
  • Every 2 weeks for the next 6 months
  • Monthly after 12 months of continuous therapy
  • Continued monitoring for 4 weeks after medication is stopped 2

Management Guidelines for WBC Changes

• If WBC drops below 2,000/mm³ or ANC below 1,000/mm³, stop medication immediately, monitor for infection with daily blood counts, and consider hematological consultation 2
• If WBC is 2,000-3,000/mm³ or ANC is 1,000-1,500/mm³, stop medication immediately, monitor for infection with daily blood counts, and may resume when WBC >3,000/mm³ and ANC >1,500/mm³ with no signs of infection 2
• For leukocytosis (elevated WBC), monitoring should continue as scheduled, but the condition should be documented and potentially investigated for other causes if persistent or extreme 1

Risk Factors for Hematological Effects

• The risk of agranulocytosis increases with age and is higher among women 4
• Youth may have higher rates of agranulocytosis compared to adults 2
• Most cases of agranulocytosis (84%) occur within the first 3 months of treatment 4
• The cumulative incidence of agranulocytosis is approximately 0.80% at 1 year and 0.91% at 1.5 years 4

Clinical Considerations

• The Clozaril National Registry (CNR) has helped reduce clozapine-related morbidity and mortality by enforcing a "no blood, no drug" policy 5
• Late-onset agranulocytosis is rare but can occur even after many years of treatment, with cases reported after 19 years of continuous clozapine monotherapy 6
• The agranulocytosis is usually reversible if the drug is stopped immediately 2

Common Pitfalls to Avoid

• Failing to obtain baseline WBC counts before initiating treatment 2
• Not adhering to the required monitoring schedule 2
• Ignoring small drops in WBC or ANC 2
• Continuing clozapine when WBC/ANC values fall below critical thresholds 2
• Overlooking WBC elevations (leukocytosis) which may sometimes precede agranulocytosis 3, 1