Clozapine and agranulocytosis in Spain: Do we have a safer population? A 5-year haematologic follow-up

Pons, Amadeu; Undurraga, Juan; Batalla, Albert; Bernardo, Miquel

doi:10.1016/j.rpsmen.2012.04.007

Cited by 6 publications

(6 citation statements)

References 30 publications

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“…The finding of spikes in WBC and neutrophils is congruent with the existing literature 12,18 ; in addition, we found clear elevations in monocytes, eosinophils, platelets and, to a lesser extent, basophils but no changes in RBCs and lymphocytes. These elevations can be observed from the first week of clozapine treatment, are transient, and seem to resolve by week 10, as in the case for eosinophils.…”

Section: Discussionsupporting

confidence: 93%

“…9 Because the introduction of mandatory monitoring, there have, although, been numerous reports of other hematological abnormalities. 10 Neutrophilia, [11][12][13] neutropenia, 11 eosinophilia, 11,14 thrombocytosis, 15 and thrombocytopenia 16,17 are examples of commonly reported aberrations in conjunction with clozapine use. Some of these anomalies (eg, leukocytosis 18 and eosinophilia 19 ) have been reported as harbingers of neutropenia or agranulocytosis, resulting in the premature discontinuation of clozapine in some instances.…”

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confidence: 99%

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The Effect of Clozapine on Hematological Indices

Lee

Takeuchi

Fervaha

et al. 2015

Journal of Clinical Psychopharmacology

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Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

The Effect of Clozapine on Hematological Indices

Lee

Takeuchi

Fervaha

et al. 2015

Journal of Clinical Psychopharmacology

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“…Se incluyeron cuatro estudios que reportaron la evaluación de la agranulocitosis en pacientes que usaban clozapina 3,[21][22][23] ; también se consideró la evidencia presentada en los resultados de las comparaciones cabeza a cabeza entre antipsicóticos para el desenlace de agranulocitosis 20,22,24 . En la tabla 1 se presentan los resultados de los estudios incluidos de la búsqueda de esta pregunta.…”

Section: Descripción De Los Hallazgos Y Calidad De La Evidenciaunclassified

“…A diferencia de los estudios anteriores, Pons 2012 23 , en un seguimiento a cinco a ños, no halló ningún caso incidente en 271 sujetos y, a diferencia de los otros estudios, se encontró un aumento del conteo de leucocitos al inicio del tratamiento.…”

Section: Descripción De Los Hallazgos Y Calidad De La Evidenciaunclassified

Evaluación y seguimiento hematológico del paciente con diagnóstico de esquizofrenia

Martínez

Peñaranda

Valencia

et al. 2015

Revista Colombiana de Psiquiatría

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“…However, the introduction of mandatory haematological monitoring for clozapine suggested that clozapine was associated with both agranulocytosis (defined, in respect to clozapine use, as neutrophils <0.5 × 10 9 /L) and neutropenia (usually defined as a neutrophil count of <1.5 × 10 9 /L; sometimes <2 × 10 9 /L). In patients registered on formal clozapine monitoring schemes, the incidence of neutropenia has been reported to range from 2.5 5 to 5.5% 6 and the incidence of agranulocytosis from 0% 7 , 8 to as much as 1% 6 , 9 . Clozapine remains underutilised because of the fear of both neutropenia and agranulocytosis and because of the burden imposed by regular blood testing 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis

et al. 2022

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The wider use of clozapine is limited by the risk of agranulocytosis and the associated requirement for monitoring of neutrophil counts. We searched local electronic patient records for cases of agranulocytosis occurring during clozapine treatment during the period 2007–2020. We found 23 episodes recorded as agranulocytosis in clozapine patients. Of these, nine met pre-defined criteria and were considered episodes of life-threatening agranulocytosis (LTA). These episodes of clozapine-induced LTA exhibited a distinct pattern of continuous and rapid neutrophil count decline to zero or near zero. Mean time for neutrophils to fall from ANC > 2 to ANC <0.5 × 109/L was 8.4 days (range 2–15 days). Each event was also characterised by a prolonged nadir and delayed recovery (range 4–16 days). Non-LTA episodes were, in contrast, brief and benign. We conclude that an important proportion of cases of agranulocytosis identified in people prescribed clozapine are not life-threatening and may not even be clozapine-related. Monitoring schemes should aim to identify true clozapine-induced LTA as opposed to threshold-defined nominal agranulocytosis. Genetics studies might benefit from examining associations with clozapine-induced LTA rather than with recorded cases of agranulocytosis or neutropenia.

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Clozapine and agranulocytosis in Spain: Do we have a safer population? A 5-year haematologic follow-up

Cited by 6 publications

References 30 publications

The Effect of Clozapine on Hematological Indices

The Effect of Clozapine on Hematological Indices

Evaluación y seguimiento hematológico del paciente con diagnóstico de esquizofrenia

Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis

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