Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-25T07:00:29.152Z Has data issue: false hasContentIssue false

14 - Eosinophilia, Leukocytosis, Thrombocytopenia, Thrombocytosis, Anemia, Hepatic Function Abnormalities

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer  and
Stephen M. Stahl
Jonathan M. Meyer
Affiliation:
University of California, San Diego
Stephen M. Stahl
Affiliation:
University of California, San Diego
Get access

Summary

One need not specialize in hematology to prescribe clozapine, but the concern about neutropenia compels all clinicians to develop expertise with concepts such as benign ethnic neutropenia (BEN), and the dose-dependent impact of divalproex/valproate on neutrophil counts and neutropenia risk. The mandatory monitoring has also revealed a propensity for clozapine to induce other hematological abnormalities including eosinophilia, neutrophilia, abnormal platelet counts, and anemia. This spectrum of hematologic abnormalities is not unique to clozapine, but an analysis of 285 antipsychotic-treated patients found that persistent anemia, neutrophilia and eosinophilia occurred at significantly higher rates compared to other antipsychotics during the first 18 weeks of therapy. A retrospective Canadian study of 1-year hematologic outcomes among 101 new clozapine starts found a cumulative incidence of 48.9% for neutrophilia (> 7500/mm3), 5.9% for eosinophilia (> 1500/mm3), and 3% each for thrombocytosis (> 500,000/mm3) and thrombocytopenia (< 100,000/mm3). An Italian study of 2404 patients reported a leukocytosis rate of 7.7% using the total WBC threshold of 15,000/mm3. Most of the aberrations were self-limited and did not necessitate treatment interruption. Anemia may have multiple causes, and one study of 96 new clozapine starts found that 24.5% developed anemia during the first 2 years of treatment, but it was not a cause of treatment discontinuation.

Type
Chapter
Information
The Clozapine Handbook
Stahl's Handbooks
 , pp. 258 - 275
Publisher: Cambridge University Press
Print publication year: 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Fabrazzo, M., Prisco, V., Sampogna, G., et al. (2017). Clozapine versus other antipsychotics during the first 18 weeks of treatment: A retrospective study on risk factor increase of blood dyscrasias. Psychiatry Research, 256, 275–282.Google Scholar
Lee, J., Takeuchi, H., Fervaha, G., et al. (2015). The effect of clozapine on hematological indices: A 1-year follow-up study. Journal of Clinical Psychopharmacology, 35, 510–516.Google Scholar
Lambertenghi Deliliers, G. (2000). Blood dyscrasias in clozapine-treated patients in Italy. Haematologica, 85, 233–237.Google ScholarPubMed
Lee, J., Bies, R., Bhaloo, A., et al. (2015). Clozapine and anemia: A 2-year follow-up study. Journal of Clinical Psychiatry, 76, 1642–1647.CrossRefGoogle ScholarPubMed
Nasreddine, W. and Beydoun, A. (2008). Valproate-induced thrombocytopenia: A prospective monotherapy study. Epilepsia, 49, 438–445.CrossRefGoogle ScholarPubMed
Acharya, S. and Bussel, J. B. (2000). Hematologic toxicity of sodium valproate. Journal of Pediatric Hematology and Oncology, 22, 62–65.CrossRefGoogle ScholarPubMed
Chateauvieux, S., Eifes, S., Morceau, F., et al. (2011). Valproic acid perturbs hematopoietic homeostasis by inhibition of erythroid differentiation and activation of the myelo-monocytic pathway. Biochemical Pharmacology, 81, 498–509.CrossRefGoogle ScholarPubMed
Nielsen, J., Correll, C. U., Manu, P., et al. (2013). Termination of clozapine treatment due to medical reasons: When is it warranted and how can it be avoided? Journal of Clinical Psychiatry, 74, 603–613.CrossRefGoogle ScholarPubMed
Hummer, M., Kurz, M., Kurzthaler, I., et al. (1997). Hepatotoxicity of clozapine. Journal of Clinical Psychopharmacology, 17, 314–317.Google Scholar
Erdogan, A., Kocabasoglu, N., Yalug, I., et al. (2004). Management of marked liver enzyme increase during clozapine treatment: A case report and review of the literature. International Journal of Psychiatry in Medicine, 34, 83–89.Google Scholar
Akuthota, P. and Weller, P. F. (2012). Eosinophils and disease pathogenesis. Seminars in Hematology, 49, 113–119.Google Scholar
McArdle, P. A., Siskind, D. J., Kolur, U., et al. (2016). Successful rechallenge with clozapine after treatment associated eosinophilia. Australasian Psychiatry, 24, 365–367.Google Scholar
Manu, P., Lapitskaya, Y., Shaikh, A., et al. (2018). Clozapine rechallenge after major adverse effects: Clinical guidelines based on 259 cases. American Journal of Therapeutics, 25, e218–e223.Google Scholar
Ho, Y. C. and Lin, H. L. (2017). Continuation with clozapine after eosinophilia: A case report. Annals of General Psychiatry, 16, 46.Google Scholar
Pollmacher, T., Fenzel, T., Mullington, J., et al. (1997). The influence of clozapine treatment on plasma granulocyte colony-stimulating (G-CSF) levels. Pharmacopsychiatry, 30, 118–121.Google Scholar
Hummer, M., Kurz, M., Barnas, C., et al. (1994). Clozapine-induced transient white blood count disorders. Journal of Clinical Psychiatry, 55, 429–432.Google ScholarPubMed
Madhusoodanan, S., Cuni, L., Brenner, R., et al. (2007). Chronic leukocytosis associated with clozapine: A case series. Journal of Clinical Psychiatry, 68, 484–488.Google Scholar
Sopko, M. A. and Caley, C. F. (2010). Chronic leukocytosis associated with clozapine treatment. Clinical Schizophrenia & Related Psychoses, 4, 141–144.Google Scholar
Focosi, D., Azzara, A., Kast, R. E., et al. (2009). Lithium and hematology: Established and proposed uses. Journal of Leukocyte Biology, 85, 20–28.CrossRefGoogle ScholarPubMed
Trinidad, E. D., Potti, A. and Mehdi, S. A. (2000). Clozapine-induced blood dyscrasias. Haematologica, 85, E02.Google ScholarPubMed
Rodeghiero, F., Stasi, R., Gernsheimer, T., et al. (2009). Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: Report from an international working group. Blood, 113, 2386–2393.Google Scholar
Kadir, R. A. and McLintock, C. (2011). Thrombocytopenia and disorders of platelet function in pregnancy. Seminars in Thrombosis and Hemostasis, 37, 640–652.CrossRefGoogle ScholarPubMed
Kate, N., Grover, S., Aggarwal, M., et al. (2013). Clozapine associated thrombocytopenia. Journal of Pharmacology and Pharmacotherapy, 4, 149–151.Google Scholar
Atmaca, M., Kilic, F., Temizkan, A., et al. (2013). What about platelet counts in clozapine users? Reviews of Recent Clinical Trials, 8, 74–77.Google Scholar
Lee, J., Powell, V. and Remington, G. (2014). Mean platelet volume in schizophrenia unaltered after 1 year of clozapine exposure. Schizophrenia Research, 157, 134–136.Google Scholar
Conley, E. L., Coley, K. C., Pollock, B. G., et al. (2001). Prevalence and risk of thrombocytopenia with valproic acid: Experience at a psychiatric teaching hospital. Pharmacotherapy, 21, 1325–1330.CrossRefGoogle Scholar
Vasudev, K., Keown, P., Gibb, I., et al. (2010). Hematological effects of valproate in psychiatric patients: What are the risk factors? Journal of Clinical Psychopharmacology, 30, 282–285.Google Scholar
Gonzales, M. F., Elmore, J. and Luebbert, C. (2000). Evidence for immune etiology in clozapine-induced thrombocytopenia of 40 months’ duration: A case report. CNS Spectrums, 5, 17–18.CrossRefGoogle ScholarPubMed
Malenica, M., Prnjavorac, B., Bego, T., et al. (2017). Effect of cigarette smoking on haematological parameters in a healthy population. Medical Archives, 71, 132–136.Google Scholar
Morlan-Coarasa, M. J., Arias-Loste, M. T., Ortiz-Garcia de la Foz, V., et al. (2016). Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: A 3-year prospective randomized interventional study. Psychopharmacology (Berlin), 233, 3947–3952.CrossRefGoogle ScholarPubMed
Gaertner, H. J., Fischer, E. and Hoss, J. (1989). Side effects of clozapine. Psychopharmacology (Berlin), 99(Suppl), S97–100.Google Scholar
Douros, A., Bronder, E., Andersohn, F., et al. (2015). Drug-induced liver injury: Results from the hospital-based Berlin Case-Control Surveillance Study. British Journal of Clinical Pharmacology, 79, 988–999.CrossRefGoogle ScholarPubMed
Wu Chou, A. I., Lu, M. L. and Shen, W. W. (2014). Hepatotoxicity induced by clozapine: A case report and review of literature. Neuropsychiatric Disease and Treatment, 10, 1585–1587.Google ScholarPubMed
Eggert, A. E., Crismon, M. L., Dorson, P. G., et al. (1994). Clozapine rechallenge after marked liver enzyme elevation. Journal of Clinical Psychopharmacology, 14, 425–426.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×