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The article reports a case of FN arising in the setting of clozapine-induced agranulocytosis (CIA) superimposed on myelodysplastic syndrome with excess type 2 blasts (MDS-EB2). Clozapine-related agranulocytosis remains incompletely understood as an idiosyncratic reaction. In the described case, neutropenia persisted with a continued decline even after stopping clozapine and starting targeted antibiotics, leading to myelogram and bone biopsy findings consistent with MDS-EB2. The overlapping conditions increased severity and worsened prognosis, necessitating frequent hematology and psychiatry collaboration.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/febrile-neutropenia-in-the-context-of-clozapine-induced-agranulocytosis-cia-and-myelodysplastic-syndrome-importance-of-a-multidisciplinary-approach/458863/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/febrile-neutropenia-in-the-context-of-clozapine-induced-agranulocytosis-cia-and-myelodysplastic-syndrome-importance-of-a-multidisciplinary-approach/458863.png","ImageObject",300,407,{"name":92,"@type":93},"Blue Pony","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What defines febrile neutropenia in the article?","Question",{"text":112,"@type":113},"Febrile neutropenia is defined using oral temperature thresholds and an absolute neutrophil count cutoff, with criteria including expected decline over the next 48 hours.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why did the clinicians continue evaluation after stopping clozapine and starting antibiotics?",{"text":117,"@type":113},"Neutropenia continued to worsen despite discontinuation of clozapine and targeted antibiotic therapy, prompting further diagnostic workup including a myelogram and bone biopsy.",{"name":119,"@type":110,"acceptedAnswer":120},"What underlying hematologic condition was ultimately identified?",{"text":121,"@type":113},"The diagnostic findings were consistent with myelodysplastic syndrome with excess type 2 blasts (MDS-EB2), superimposed on the clozapine-associated agranulocytosis setting.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},458863,1791476269,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962090760266,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Review began 11/05/2025  \nReview ended 11/29/2025  \nPublished 12/09/2025  \n© Copyright 2025  \nConchinha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CCBY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited.  \nDOI: 10.7759/cureus.98805  \nOpen Access Case Report  \nFebrile Neutropenia in the Context of ClozapineInduced Agranulocytosis (CIA) and Myelodysplastic Syndrome: Importance of a Multidisciplinary Approach  \nAndré Filipe Conchinha 1 , Tiago Pack 2, Afonso Rodrigues 3 , Adriana Lopes 3, António Santos 3  \n1. Internal Medicine, Centro Hospital Universitário de Lisboa Central, Lisbon, PRT 2. Internal Medicine, Hospital dos Lusíadas, Lisbon, PRT 3. Internal Medicine, Hospital de Santa Marta, Unidade Local de Saúde de São José, Lisbon, PRT  \nCorresponding author: André Filipe Conchinha, [andre.f.conchinha@gmail.com](andre.f.conchinha@gmail.com)  \nAbstract  \nFebrile neutropenia (FN) constitutes a medical emergency, with significant associated mortality, and should be addressed by a multidisciplinary team. We present a case of FN in the context of clozapine-induced agranulocytosis (CIA) superimposed on myelodysplastic syndrome with excess type 2 blasts (MDS-EB2) . The mechanism by which clozapine induces agranulocytosis remains unclear, but it represents an idiosyncratic reaction affecting few patients. In the case described, neutropenia maintained a downward kinetics (nadir 0 neutrophils) even after discontinuation of the antipsychotic and the institution of targeted antibiotic therapy, which prompted a myelogram and bone biopsy, consistent with myelodysplastic syndrome. This overlapping of pathologies has contributed to the severity of the neutropenia and leads to a worse prognosis. The complexity of the case required frequent collaboration with other specialties (hematology and psychiatry) .  \nCategories: Hematology, Psychiatry, Internal Medicine  \nKeywords: clozapine-induced agranulocytosis, febrile neutropenia, leukopenia, myelodysplastic syndrome (mds),  \nmyelogram  \nIntroduction  \nNeutrophils play a key role in the body 's defense against infections, particularly in bacterial and fungal infections. Neutropenia is a decrease in the absolute neutrophil count (\u003C1500/μL), and the risk of infection  \ndirectly depends on its severity and duration [1-3].  \nNeutrophil depletion can occur through three pathophysiological mechanisms: decreased bone marrow production (congenital abnormalities; hematologic or infiltrative infectious disease; myelotoxic drugs; or  \nnutritional deficiencies) ; the transfer of circulating neutrophils to secondary lymphoid tissues or the  \nendothelium, a phenomenon called marginalization (as can occur in hypersplenism or splenomegaly) ; and  \nimmune destruction of circulating neutrophils (pharmacological effect or autoimmune mechanism) .  \nTreatment should be directed at the underlying cause, and granulocyte colony-stimulating agents may be necessary [3,4] . Febrile neutropenia (FN) is defined as an oral temperature ≥ 38 .3°C, or > 38°C maintained for more than one hour, and an absolute neutrophil count \u003C 500/μL, or \u003C 1000/μL with a predicted decline to \u003C  \n500/μL within the next 48 hours [5] . FN constitutes a medical emergency, as it is associated with high  \nmortality and morbidity, and should be addressed by a multidisciplinary team. Treatment requires early initiation of antibiotic therapy, ideally after appropriate cultures [3-5]. In this case, we describe iatrogenic drug-induced neutropenia in a patient who concomitantly presented a myelodysplastic syndrome with  \nexcess type 2 blasts (MDS-EB2) .  \nCase Presentation  \nA 71-year-old female patient lived alone and was independent in activities of daily living. She had a known  \nmedical history of hypertension, dyslipidemia, hypothyroidism, and bipolar disorder. Her medications  \nincluded enalapril 5 ","cbCaibZUPb7OhUse","https://ap.wps.com/l/cbCaibZUPb7OhUse","pdf",267546,"English","# Abstract\n# Introduction\n# Case Presentation\n## Treatment and clinical course","[{\"question\":\"What defines febrile neutropenia in the article?\",\"answer\":\"Febrile neutropenia is defined using oral temperature thresholds and an absolute neutrophil count cutoff, with criteria including expected decline over the next 48 hours.\"},{\"question\":\"Why did the clinicians continue evaluation after stopping clozapine and starting antibiotics?\",\"answer\":\"Neutropenia continued to worsen despite discontinuation of clozapine and targeted antibiotic therapy, prompting further diagnostic workup including a myelogram and bone biopsy.\"},{\"question\":\"What underlying hematologic condition was ultimately identified?\",\"answer\":\"The diagnostic findings were consistent with myelodysplastic syndrome with excess type 2 blasts (MDS-EB2), superimposed on the clozapine-associated agranulocytosis setting.\"}]","Febrile Neutropenia in the Context of Clozapine-Induced Agranulocytosis (CIA) and Myelodysplastic Syndrome - Importance of a Multidisciplinary Approach | PDF",1790754637,13]