Febrile Neutropenia in the Context of Clozapine-Induced Agranulocytosis (CIA) and Myelodysplastic Syndrome - Importance of a Multidisciplinary Approach

Q: What defines febrile neutropenia in the article?

Febrile neutropenia is defined using oral temperature thresholds and an absolute neutrophil count cutoff, with criteria including expected decline over the next 48 hours.

Q: Why did the clinicians continue evaluation after stopping clozapine and starting antibiotics?

Neutropenia continued to worsen despite discontinuation of clozapine and targeted antibiotic therapy, prompting further diagnostic workup including a myelogram and bone biopsy.

Q: What underlying hematologic condition was ultimately identified?

The diagnostic findings were consistent with myelodysplastic syndrome with excess type 2 blasts (MDS-EB2), superimposed on the clozapine-associated agranulocytosis setting.

Sep 30, 2026

Uploaded by Blue Pony

Febrile neutropenia (FN) constitutes a medical emergency with substantial mortality and morbidity and requires management by a multidisciplinary team. 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.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Abstract

Introduction

Case Presentation

Treatment and clinical course

Review began 11/05/2025 Review ended 11/29/2025 Published 12/09/2025 © Copyright 2025 Conchinha 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. DOI: 10.7759/cureus.98805 Open Access Case Report Febrile Neutropenia in the Context of ClozapineInduced Agranulocytosis (CIA) and Myelodysplastic Syndrome: Importance of a Multidisciplinary Approach André Filipe Conchinha 1 , Tiago Pack 2, Afonso Rodrigues 3 , Adriana Lopes 3, António Santos 3 1. 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 Corresponding author: André Filipe Conchinha, [andre.f.conchinha@gmail.com](andre.f.conchinha@gmail.com) Abstract Febrile 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) . Categories: Hematology, Psychiatry, Internal Medicine Keywords: clozapine-induced agranulocytosis, febrile neutropenia, leukopenia, myelodysplastic syndrome (mds), myelogram Introduction Neutrophils 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 (<1500/μL), and the risk of infection directly depends on its severity and duration [1-3]. Neutrophil depletion can occur through three pathophysiological mechanisms: decreased bone marrow production (congenital abnormalities; hematologic or infiltrative infectious disease; myelotoxic drugs; or nutritional deficiencies) ; the transfer of circulating neutrophils to secondary lymphoid tissues or the endothelium, a phenomenon called marginalization (as can occur in hypersplenism or splenomegaly) ; and immune destruction of circulating neutrophils (pharmacological effect or autoimmune mechanism) . Treatment 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 < 500/μL, or < 1000/μL with a predicted decline to < 500/μL within the next 48 hours [5] . FN constitutes a medical emergency, as it is associated with high mortality 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 excess type 2 blasts (MDS-EB2) . Case Presentation A 71-year-old female patient lived alone and was independent in activities of daily living. She had a known medical history of hypertension, dyslipidemia, hypothyroidism, and bipolar disorder. Her medications included enalapril 5

FAQs

What defines febrile neutropenia in the article?

Febrile neutropenia is defined using oral temperature thresholds and an absolute neutrophil count cutoff, with criteria including expected decline over the next 48 hours.

Why did the clinicians continue evaluation after stopping clozapine and starting antibiotics?

Neutropenia continued to worsen despite discontinuation of clozapine and targeted antibiotic therapy, prompting further diagnostic workup including a myelogram and bone biopsy.

What underlying hematologic condition was ultimately identified?

The diagnostic findings were consistent with myelodysplastic syndrome with excess type 2 blasts (MDS-EB2), superimposed on the clozapine-associated agranulocytosis setting.

Sep 30, 2026

Uploaded by Blue Pony