Agranulocytosis

INTRODUCTION: Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of propylthiouracil (PTU) is also contraindicated. Few reports exist about the optimal alternative treatment regimens for the management of thyrotoxicosis in these medically complex patients in the pediatric population. CASE REPORT: We report prolonged saturated solution of potassium Iodide (SSKI) use (29 days) in a 17-year-old female with GD and MMI-induced agranulocytosis, who presented with septic shock...

KEY CLINICAL MESSAGE: Most drugs that cause adverse events are difficult to identify in critically ill patients undergoing polypharmacy. We share our experience in identifying the causative drug among four suspect drugs administered during emergency treatment. ABSTRACT: We present the case of a 93-year-old man who was admitted for the treatment of cerebrovascular events. The patient was initially prescribed dual antiplatelet therapy with aspirin and clopidogrel along with lansoprazole, Hange-koboku-toh, and elobixibat...

INTRODUCTION: With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice. CASE REPORT: We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy. MANAGEMENT AND OUTCOME: Pembrolizumab was discontinued immediately...

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Idiosyncratic adverse events to phenytoin therapy, such as agranulocytosis and acute liver failure, though rare, may be life-threatening. Simultaneous occurrence of both adverse events is exceedingly rare; only two cases have been reported in the literature to date. We describe such a case in a 15-year-old girl. Prompt haematological and hepatic recovery occurred after discontinuation of the drug. Given the widespread use of phenytoin in seizure disorders, clinicians prescribing this drug should be aware of its potential complications...

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice...

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient...

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8...

Most idiosyncratic drug reactions (IDRs) appear to be immune-mediated, but mechanistic events preceding severe reaction onset remain poorly defined. Damage-associated molecular patterns (DAMPs) may contribute to both innate and adaptive immune phases of IDRs, and changes in extracellular vesicle (EV) cargo have been detected post-exposure to several IDR-associated drugs. To explore the hypothesis that EVs are also a source of DAMPs in the induction of the immune response preceding drug-induced agranulocytosis, the proteome and immunogenicity of clozapine- (agranulocytosis-associated drug) and olanzapine- (non-agranulocytosis-associated drug) exposed EVs were compared in two preclinical models: THP-1 macrophages and Sprague Dawley rats...

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage. PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0...

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases...

Anecdotal evidence of superior efficacy and lack of extrapyramidal symptoms in treating schizophrenia made clozapine a promising therapy in the United States during the early 1970s. In 1975, however, numerous fatal cases of clozapine-related agranulocytosis in Finland nearly ended the drug's development. Convinced of the significant benefits to patients, some clinicians in the United States advocated having clozapine available on a case-by-case humanitarian basis, which eventually helped resurrect the drug for Food and Drug Administration approval in 1989...

Pure white cell aplasia (PWCA) is a very rare hematological disorder with a nearly total absence of granulocytes and their precursor cells. While the disease is rarely diagnosed incidentally in otherwise asymptomatic individuals, most patients suffer from sometimes life-threatening infections. Due to its very low incidence, the precise pathomechanism of PWCA still needs to be elucidated. While most cases reported in the literature have been associated with an underlying thymic or autoimmune disease, some other factors including the intake of certain drugs such as antimicrobial agents or immune checkpoint inhibitors have been identified as potential triggers...

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes...

BACKGROUND: Most patients with lower risk myelodysplastic neoplasms (MDS) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron overloaded RBC transfusion-dependent patients with lower risk MDS...

Granulocytes and macrophages are the frontline defenders of the innate immune system. These myeloid cells play a crucial role in not only eliminating pathogens and tumor cells, but also regulating adaptive immune responses. In neonatal sepsis and post-chemotherapy agranulocytosis, the absence of these cells leaves the host highly vulnerable to infections. Beyond replacement to prevent or control neutropenic sepsis, engineered myeloid cells may offer distinct opportunities for cell therapies. For example, the mobility and specific homing capacities of neutrophils to sites of inflammation could be exploited to deliver biocidal agents, or anti-inflammatory healing signals during sepsis, autoimmunity, and organ transplantation...

Agranulocytosis is a rare but life-threatening complication of methimazole and propylthiouracil, antithyroid drugs (ATDs) prescribed for the treatment of hyperthyroidism. We report the case of a 41-year-old female who presented to our institution with complaints of fevers, chills, sore throat, myalgias, and generalized weakness one month after treatment initiation with methimazole. A complete blood count at admission revealed agranulocytosis with an absolute neutrophil count of 0/μl...

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia. In Japan, its use requires management by a blood monitoring system called the Clozaril Patient Monitoring Service (CPMS) for the early detection of serious side effects such as agranulocytosis, which is extremely rare. Monitoring services vary among the clozapine suppliers in different countries. Additionally, Japanese patients can be started on clozapine treatment exclusively through an 18-week inpatient admission at a psychiatric hospital capable of coordinating with a hematologist...

There is growing interest in clozapine clinical use, monitoring, and research, particularly adverse drug reactions (ADRs) other than agranulocytosis. In this study we focused on clozapine pharmacovigilance. Hence, we contacted clinicians and researchers in Latin America and requested information about local psychiatric services, clozapine availability, clinical use, and ADR monitoring with the VigiBase system. Only two countries have the minimum recommended number of psychiatric beds (15 per 100,000 residents): Uruguay (N = 34...

Reticular dysgenesis (RD) is a rare genetic disease caused by gene mutations in the ATP:AMP phosphotransferase, adenylate kinase 2 (AK2). Patients with RD suffer from severe combined immunodeficiency with neutrophil maturation arrest. Although hematopoietic stem cell transplantation can be a curative option, it is invasive, and complications of agranulocytosis-induced infection worsen the prognosis. Here, we report that the use of UK-5099, an inhibitor of the mitochondrial pyruvate carrier (MPC), on hemo-angiogenic progenitor cells (HAPCs) derived from AK2-deficient induced pluripotent stem cells improved neutrophil maturation...