Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature

Abstract

Background and Objectives: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. Materials and Methods: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. Results: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. Conclusions: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics

“…However, there are more cases where the hematological effect of clozapine manifests as leukocytosis and neutrophilia (Lee et al ., 2015; Fabrazzo et al ., 2017). According to one theory, the release of cytokines, including G-CSF, promotes the expression of anti-apoptotic proteins, tipping the scale toward blood cell survival (Fehsel et al ., 2005; Liu et al ., 2011; Paribello et al ., 2021). In a case series reported by Butler et al .…”

Decoding Clozapine-Induced Agranulocytosis: Unraveling Interactions and Mitigation Strategies

“…These conditions weaken the immune system and increase the susceptibility to infections when combined with clozapine. In contrast, some evidence suggests that leukocytosis from clozapine treatment may be harmless, questioning whether preexisting leukopenia exacerbates the risk of agranulocytosis [ 47 ]. Chen et al [ 48 ] emphasized the role of genetic factors in managing clozapine treatment in individuals with preexisting disorders.…”

Application and investigation of thrombopoiesis-stimulating agents in the treatment of thrombocytopenia

“…88 However, its stimulating effects on the hematopoietic system, such as agranulocytosis, leukocytosis, and thrombocytosis, are recognized as significant side effects. 89,90 A follow-up study about clozapine’s stimulating effect on patients’ thrombopoiesis of a 1-year period demonstrated that since the beginning of clozapine treatment in the first week, platelet counts increased synchronically but transiently, and the early spike in platelet counts reflected raised IL-6 levels, which induced thrombopoiesis through the gp130 signaling and interaction with IL-3 and THPO. 91,92 This result suggests that IL-6 might be the crucial factor in clozapine-induced thrombocytosis.…”