Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis
Abstract 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 ep...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | npj Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-022-00232-0 |
| _version_ | 1797642827715313664 |
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| author | David Taylor Kalliopi Vallianatou Eromona Whiskey Olubanke Dzahini James MacCabe |
| author_facet | David Taylor Kalliopi Vallianatou Eromona Whiskey Olubanke Dzahini James MacCabe |
| author_sort | David Taylor |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T14:05:55Z |
| format | Article |
| id | doaj.art-2010d91e70e34923aba72fc54f5700d0 |
| institution | Directory Open Access Journal |
| issn | 2334-265X |
| language | English |
| last_indexed | 2024-03-11T14:05:55Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Schizophrenia |
| spelling | doaj.art-2010d91e70e34923aba72fc54f5700d02023-11-02T02:01:02ZengNature Portfolionpj Schizophrenia2334-265X2022-03-01811910.1038/s41537-022-00232-0Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosisDavid Taylor0Kalliopi Vallianatou1Eromona Whiskey2Olubanke Dzahini3James MacCabe4Institute of Pharmaceutical Science, King’s College LondonPharmacy Department, Maudsley HospitalInstitute of Pharmaceutical Science, King’s College LondonInstitute of Pharmaceutical Science, King’s College LondonNational Psychosis Unit, Bethlem Royal HospitalAbstract 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.https://doi.org/10.1038/s41537-022-00232-0 |
| spellingShingle | David Taylor Kalliopi Vallianatou Eromona Whiskey Olubanke Dzahini James MacCabe Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis npj Schizophrenia |
| title | Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis |
| title_full | Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis |
| title_fullStr | Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis |
| title_full_unstemmed | Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis |
| title_short | Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis |
| title_sort | distinctive pattern of neutrophil count change in clozapine associated life threatening agranulocytosis |
| url | https://doi.org/10.1038/s41537-022-00232-0 |
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