What are the effects of quetiapine (antipsychotic medication) on the total leukocyte count (TLC) in patients, particularly those with a history of blood disorders?

Effects of Quetiapine on Total Leukocyte Count

Quetiapine can cause leukopenia, neutropenia, and thrombocytopenia, though these hematological effects are less common than with clozapine; however, patients with pre-existing low white blood cell counts or history of drug-induced blood disorders require close monitoring with complete blood counts, particularly during the first few months of therapy. 1

Hematological Risk Profile

Documented Blood Count Effects

• Leukopenia and neutropenia have been reported temporally related to quetiapine treatment in both clinical trials and post-marketing surveillance 1
• In adult placebo-controlled monotherapy trials, neutrophil counts <1.0 x 10⁹/L occurred in 0.3% (10/2967) of quetiapine-treated patients versus 0.1% (2/1349) of placebo patients 1
• Agranulocytosis (absolute neutrophil count <500/mm³) has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors 1
• Thrombocytopenia can occur concurrently with leukopenia, as documented in case reports showing reversible but potentially fatal hematological toxicity 2, 3

Pediatric Considerations

• The American Academy of Child and Adolescent Psychiatry reports one unpublished case of a precipitous drop in absolute neutrophil count (ANC) and platelets in a 12-year-old boy receiving quetiapine 4
• Although primarily associated with clozapine, agranulocytosis can occur with any antipsychotic agent, including quetiapine 4

Clinical Monitoring Algorithm

Baseline Assessment

• Obtain complete blood count (CBC) with differential before initiating quetiapine therapy 4, 1
• Document any pre-existing low white blood cell count or history of drug-induced leukopenia/neutropenia, as these are major risk factors 1

High-Risk Patient Identification

Patients requiring intensive monitoring include those with:

• Pre-existing low WBC at baseline 1
• History of drug-induced leukopenia/neutropenia from any medication 1
• Benign ethnic neutropenia or genetic susceptibility to low white blood cell counts 5

Monitoring Schedule

For high-risk patients:

• Monitor CBC frequently during the first few months of therapy 1
• Discontinue quetiapine at the first sign of WBC decline in the absence of other causative factors 1

For all patients:

• Consider neutropenia in any patient presenting with infection, particularly without obvious predisposing factors 1
• Evaluate unexplained fever promptly with CBC 1

Management of Hematological Abnormalities

Neutropenia Response Protocol

Severe neutropenia (ANC <1000/mm³):

• Immediately discontinue quetiapine 1
• Follow WBC until recovery 1
• Do not rechallenge with quetiapine 1

Mild to moderate neutropenia:

• Carefully monitor for fever or signs of infection 1
• Treat infections promptly if they occur 1

Reversibility and Rechallenge Considerations

• Quetiapine-associated leukopenia and thrombocytopenia appears reversible upon discontinuation 2
• However, rechallenge with quetiapine can cause rapid recurrence of hematological abnormalities (within 6 days in documented cases) 2
• The hematological toxicity is possibly fatal despite reversibility, making rechallenge inadvisable 2

Comparative Risk Assessment

• Quetiapine has not been associated with agranulocytosis to the same degree as clozapine in large clinical trials 6
• There have been no reports of agranulocytosis attributed to quetiapine in initial large-scale studies, though post-marketing surveillance has documented cases 6, 1
• The incidence of significant neutropenia remains lower than with clozapine but higher than placebo 1

Critical Clinical Pitfalls

• Do not assume safety based on low-dose therapy: Low-dose quetiapine (used for sleep or mood) can still cause agranulocytosis and leukopenia in susceptible patients 5
• Do not overlook concurrent thrombocytopenia: Quetiapine can cause combined leukopenia and thrombocytopenia, not just isolated neutropenia 2, 3
• Do not rechallenge after documented hematological toxicity: Even if the patient prefers quetiapine, rechallenge risks rapid recurrence of potentially fatal blood dyscrasias 2