Case Of Agranulocytosis Research Articles

A rare case of drug-induced agranulocytosis: A challenging diagnosis andmanagement approach

Agranulocytosis is a severe adverse drug reaction characterized by a significant decrease in the number of neutrophils, making patientshighly susceptible to infections. I present a rare case of drug-induced agranulocytosis in a 45-year-old male patient who presented witha sudden onset of fever, sore throat, and severe fatigue. Infectious and autoimmune etiologies were ruled out by thorough examinations.A thorough medication history indicated that a new drug for the treatment of hypertension had just been started (chlorthalidone). Thepatient was immediately placed on broad-spectrum antibiotics and granulocyte colony-stimulating factor after the medication wasrapidly stopped. The patient’s neutrophil count gradually increased with prompt management, and he displayed clinical improvement.This instance emphasizes the value of prompt diagnosis and treatment of drug-induced agranulocytosis to avert potentially fatalconsequences.

Severe neutropenia unrelated to clozapine in patients receiving clozapine.

Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine. In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria. In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified. Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.

Drug-induced agranulocytosis – prevalence, complications, management tactics

Based on the results of a review of clinical cases and research data, the prevalence of drug-induced agranulocytosis, complications and management tactics are considered. A clinical case of agranulocytosis caused by taking nonsteroidal anti-inflammatory drugs (NSAIDs) is presented. The patient was admitted to the purulent surgical department with purulent lymphadenitis and sepsis. During the examination, agranulocytosis was revealed against the background of constant intake of NSAIDs (Aertal, Diclofenac, ibuprofen) for 3 years for joint pain. Surgical treatment was performed and antibiotic therapy was prescribed. Against the background of Filgrastim therapy, a positive dynamics of peripheral blood parameters was noted. The use of granulocyte colony stimulating factors (G-CSF) significantly reduces the severity of the disease, reduces the duration of hospitalization and mortality in patients with drug-associated agranulocytosis.

Paliperidone LAI-Induced Leukocytopenia: A Case Report

IntroductionAntipsychotics effectively manage psychotic symptoms but may have side effects. Patients with schizophrenia often lack insight into their condition, leading to nonadherence. Long-acting injectable (LAI) antipsychotics aim to overcome this, reducing relapse risks. Paliperidone LAI, a second-generation antipsychotic, has a lower side effect profile when compared to first-generation counterparts. Blood dyscrasias, like neutropenia and lymphopenia, increase infection susceptibility. This case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.ObjectivesThis case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.MethodsResultsCASEA 42-year-old female with schizophrenia, nonadherent to previously prescribed medication was admitted to our acute psychiatric department. She experienced positive symptoms (paranoid delusions), as well as disorganized thinking and behavior. Oral risperidone 4 mg two times a day was recommenced and titrated with mild improvement in her psychotic symptoms with the idea of switching to paliperidone LAI and eventually ceasing oral medication. Oral paliperidone was unavailable for prescription due to local restrictions. At admission her routine laboratory tests showed no abnormalities, but 5 days after receiving paliperidone LAI, routine laboratory tests showed a strong decrease in her WBC and absolute neutrophilic and lymphocytic count ( Lkc 2.89x109/L, Neut 1.57x 109/L, Lym 0.88x 109 /L ). Antipsychotic-induced blood dyscrasia was suspected and paliperidone depot was discontinued. The patient had rapid improvement in her WBC reaching the reference range in 10 days ( Lkc 4.23 x 109/L, Neut 2.51x10 9/L, Lym 0.98x 109/L). Sertindole was introduced consdering her history of a good therapeutic response to the drug, with improvement in psychotic symptoms. She is currently stable taking sertindole 16 mg/day, clonazepam 2 mg/day and alprazolam 0.5 mg/day.DISCUSSIONThe onset of neutropenia and lymphopenia post-paliperidone LAI initiation, resolving in 10 days,, indicate a direct association. Few cases report to date describe paliperidone-induced leukocytopenia, with rapid recovery post-discontinuation. Proposed mechanisms include bone marrow suppression and peripheral WBC destruction. It has been proposed that drug-induced neutropenia is often dose-dependent, which could explain why our patient exhibited tolerability to risperidone but developed cytopenia upon transitioning to depot paliperidone.ConclusionsWhile cases of agranulocytosis have been reported in association with the use of other antipsychotics these antipsychotics do not require the same monitoring as clozapine. Our case emphasizes the need for vigilant blood dyscrasia monitoring during antipsychotic therapy.Disclosure of InterestNone Declared

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

The Tarnished Legacy of a Wonder Drug: Revisiting the Complicated History of Clozapine.

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. This article builds on previous literature by utilizing oral histories from clinicians, researchers, and a patient's family member to understand how clozapine was saved. Exploring these stakeholders' perspectives has value to modern clinicians, who underprescribe the drug despite demonstrable benefits for treatment-resistant schizophrenia and suicide prevention.

The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) 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 MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1–2. Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.

The Rare Sore Throat: A Case of Thyroid Storm and Agranulocytosis.

Thyroid storm is a rare but potentially life-threatening metabolic disorder that presents unique management challenges in the emergency department. Thionamides are commonly used as monotherapy for first-line treatment of hyperthyroidism. In this case, a 26-year-old male presented to the emergency department with sore throat, fever, and diarrhea. He was found to have thyrotoxicosis as well as methimazole-induced bone marrow suppression resulting in agranulocytosis. Thyroid storm is a rare condition that carries a high risk of mortality and can further compromise a patient's immune system due to complications of common treatment modalities. It can potentially be misdiagnosed as sepsis due to tachycardia, febrile state, and tachypnea. This case report includes a discussion of diagnostic studies, as well as medical and surgical treatment modalities that led to the patient's recovery.

Nifedipine-induced agranulocytosis: A rare case report and literature review

Rationale: Drug-induced agranulocytosis (DIAG) is a fatal idiosyncratic reaction characterized by a peripheral neutrophil count &lt;0.5 × 109/L. Almost all classes of medications have been implicated with DIAG. However, agranulocytosis induced by antihypertensive drugs is rare worldwide. To the best of our knowledge, this is the first case of nifedipine-associated agranulocytosis with a positive rechallenge. Patient concerns: An 82-year-old man was admitted to our hospital due to uncontrolled fasting blood sugar. He had a history of hypertension and underwent treatment with nifedipine 6 years prior to admission. Blood tests showed white blood cell count of 2.30 × 109/L with a neutrophil count of 0.49 × 109/L. Diagnosis: Other malignancies that contributed to agranulocytosis were excluded, and the patient was diagnosed with DIAG. Interventions and outcomes: At first, gliclazide, rather than nifedipine, was considered as the culprit for DIAG and it was discontinued. Neutrophil count improved upon hematopoietic growth factors and traditional Chinese medicine. During the follow-up, the neutrophil count decreased again, and nifedipine was thought to be the offending agent for agranulocytosis. The neutrophil count increased to 0.91 × 109/L 2 months after nifedipine discontinuation. However, the patient was re-exposed to nifedipine and the neutrophil count decreased to 0.70 × 109/L. Lessons: Nifedipine-induced agranulocytosis is a rare but serious adverse drug reaction. For any patients with clinical suspicion or diagnosis of DIAG, a full drug history should be chronologically and completely taken in order to identify the suspected agents. Sometimes diagnosis of DIAG is challenging since some patients may be entirely asymptomatic. Management of DIAG starts with immediate discontinuation of the implicated drug. Empirical broad-spectrum antibiotics and hematopoietic growth factors may improve patient outcomes and reduce recovery time.

Fosfomycin-induced agranulocytosis: a case report and review of the literature

BackgroundThe intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal.Case presentationA 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count.ConclusionThis is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.

FRI505 A Rare Case Of Methimazole Induced Grave Agranulocytosis

Abstract Disclosure: N. Barua: None. S. Idriss: None. R. Panta: None. I. Jamal: None. J. Hodge: None. Introduction: Agranulocytosis is a rare side effect of methimazole that usually occurs in a dose-dependent fashion within the first 3 to 6 months of initiation. It occurs in 0.2 - 0.5% of patients with Graves' disease who receive treatment with antithyroid drugs (ATD). We describe a rare case of agranulocytosis in a 36-year-old female treated with methimazole for hyperthyroidism. Case: A 36-year-old female, who was diagnosed with Graves' disease 2 months prior, presented to the Emergency Department for evaluation of worsening sore throat, odynophagia, dysphagia, and fever for 12 days after failed outpatient treatment with amoxicillin. Pre-admission labs showed free T4 &amp;gt; 7.77ng/dl, TSH &amp;lt;0.01 mIU/L, thyrotropin receptor antibody elevated at 28.30. She was initially treated with methimazole 10mg TID then reduced to BID few weeks prior to hospitalization. On arrival, her temperature was 102.8 F, heart rate 120 bpm, and blood pressure 116/65 mmHg. On physical exam, she had thyromegaly and discomfort on palpation of the neck. Labs showed WBC of 0.6k/mm3, absolute neutrophil count (ANC) of 0, Hgb 11.1 g/dl, TSH &amp;lt;0.01 mIU/L, Free T4 3.11 ng/dL and free T3 6.7 pg/ml. CT neck with contrast revealed tonsillitis and epiglottitis with associated tonsillar and peritonsillar abscess. She was started on Vancomycin, Cefepime and Acyclovir for 7 days; and Fluconazole 14 days for epiglottitis, tonsillitis, HSV, and oral candidiasis. Methimazole was discontinued, and she was started on cholestyramine 4 gm 6 hourly, dexamethasone 2 mg IV 8 hourly and propranolol 20 mg 8 hourly with improvement of her free T4 from 3.11-2.93. Her free T3 worsened from 8.1 to 11.1, potassium iodide 50 mg 6 hourly was added to the regimen. After 10 days of treatment, her thyroid blood tests and ANC improved, and she was discharged. She underwent total thyroidectomy 2 weeks after discharge and was placed on levothyroxine 75 mcg daily. Conclusion: Agranulocytosis from ATDs has a remarkably high mortality rate of about 21.5%. The mechanism behind is both immune-mediated toxicity and direct toxicity from oxidative process mediated by myeloperoxidase and cytochrome P450 enzymes. Agranulocytosis caused by ATD is usually dose dependent and mostly present with significant hyperthyroid state. Alternative ways of treatment should be promptly initiated as cross-reaction between methimazole and propylthiouracil occurs in about 15.2% of cases. Patient education about this dreadful side effect and awareness about seeking immediate medical attention at symptom onset is key in successful remediation of this condition. Presentation: Friday, June 16, 2023

Successful Steroid Treatment of Pembrolizumab-induced Agranulocytosis That Developed after Splenectomy in a Patient with Non-small-cell Lung Cancer.

Neutropenia, a rare immune-related adverse event, affects patients receiving treatment with immune checkpoint inhibitors (ICIs). We herein report a case of pembrolizumab-induced agranulocytosis. An 83-year-old man was diagnosed with advanced-stage lung carcinoma concomitant with splenomegaly complicated by hypersplenism, causing pancytopenia. To avoid the risk of bone marrow suppression due to cytotoxic chemotherapy, pembrolizumab monotherapy was chosen. However, the patient developed agranulocytosis despite the resolution of pancytopenia through splenectomy performed after the fourth pembrolizumab cycle. Neutrophil counts improved after steroid treatment but not after granulocyte colony-stimulating factor treatment. This case demonstrated that neutropenia can sometimes develop abruptly after several ICI therapy cycles.

Neutropenia secondary to synthetic antithyroid drugs: about 5 cases including one case of agranulocytosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 (COVID-19). Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients. The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics. The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine. This study included 100 patients. White blood cell count changes were limited to a few cases of mild granulocytopenia (8.16% in the clozapine group and 3.92% in the nonclozapine group, P = 0.37) with no cases of severe granulocytopenia or agranulocytosis. As far as leukocyte counts are concerned, mRNA COVID-19 vaccination seems to be safe in patients treated with clozapine who previously had SARS-CoV-2 infection. Leukocyte changes had no clinical implications.

PSAT344 Zeroing In: Methimazole Induced Agranulocytosis in Amiodarone Induced Thyrotoxicosis

Abstract Background Agranulocytosis, defined as absolute neutrophil count (ANC) &amp;lt; 500/µL due to antithyroid drugs (ATDs), methimazole, carbimazole, and propylthiouracil (PTU), is a rare but serious complication with an occurrence of 0.1- 0.5%. ATDs induced agranulocytosis occurs abruptly, usually in the first three months of treatment but can occur any time after initiation of treatment, and although it is more common with a higher dose of methimazole &amp;gt; 30 mg/day, it can also occur with lower dosages. We present a rare case of agranulocytosis in a patient with Amiodarone-induced Thyrotoxicosis (AIT) with an ANC of 0/µL. Clinical Case A 68-year-old male with atrial fibrillation and heart failure was diagnosed with AIT when he presented to ED with thyrotoxicosis. Amiodarone was discontinued. Methimazole 40 mg daily with prednisone 20 mg daily was initiated. The ANC was 4360/µL. After nine weeks on methimazole, he presented with fever and tremors. The laboratory tests during this admission revealed WBC 1310/µL (4000-11000/µL) with granulocytes 0% (35%-80%), ANC 0/µL (1820-7420/µL), TSH &amp;lt; 0.01 (0.45-5.3mIU/mL), free T4 5.5 (0.58-1.64 ng/dL), free T3 4.4 (2.8-4.4 pg/dL). Methimazole was discontinued and antibiotics started. He received six doses of Granulocyte colony-stimulating factor (G-CSF) Filgrastim 480 mcg with an improvement of WBC to 6370/µL with a granulocyte count of 60% on the 6th day of admission. He eventually underwent thyroidectomy for treatment of the thyrotoxicosis. Discussion The proposed mechanism of agranulocytosis with ATDs is twofold. First, there is a direct toxic effect on mature circulating neutrophils and stem cells. The second is complement-mediated antibodies against granulocytes. Furthermore, AIT is associated with a higher risk for ATD induced agranulocytosis, although the mechanism remains elusive. The most common manifestations are fever and sore throat. The management includes discontinuation of ATD and starting antibiotics. G-CSF is used to treat agranulocytosis as it decreases the recovery time, the rate of infectious complications, and the mortality rate. Patients with ANC &amp;lt; 100/µL have a greater risk of infectious and fatal complications than patients with ANC &amp;gt; 100/µL. After resolution of agranulocytosis, methimazole or any other thionamides are generally not recommended due to concern for recurrence due to cross-reactivity among thionamides. Thyroidectomy or radioiodine therapy should be considered for definitive treatment of the hyperthyroidism in this circumstance. Conclusion Due to the low incidence and abruptness of agranulocytosis from ATDs, controversy exists over the value of routine monitoring of WBC count. This case emphasizes routine WBC monitoring could be considered in patients on higher doses of methimazole, especially in the first three months, due to the increased risk of agranulocytosis. Patient education on the life-threatening complication of ATD induced agranulocytosis is vital. It helps patients recognize early symptoms and seek medical care promptly, which aids in early intervention and reduces morbidity and mortality. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Characteristics of Graves' disease in children and adolescents in Nanjing: A retrospective investigation study.

ObjectiveThis cross-sectional study analyzed the clinical characteristics of newly diagnosed Graves' disease (GD) in children and adolescents to provide clinical evidence for the early diagnosis of GD.MethodFrom 2013 to 2019, information on children and adolescents with newly diagnosed GD admitted to the Department of Endocrinology, Children's Hospital of Nanjing Medical University, was collected, including clinical features and laboratory tests. The data were summarized and statistically analyzed.ResultThis study included 204 cases of newly diagnosed GD, with 158 females and 46 males. The average age at initial diagnosis was 8.9 ± 2.9 years. A total of 132 cases (64.7%) had symptoms before puberty, and 72 cases (35.3%) had symptoms during puberty. Goiter was detected in 193 cases (94.6%). There were 140 cases (68.6%) of exophthalmos, and 21.4% (30/140) were infiltrative. At initial diagnosis, 10 cases (4.9%) reported leukopenia, 18 cases (8.8%) reported neutropenia, and 15 cases (7.4%) reported mild anemia. There was 1 (0.5%) case of thrombocytopenia and 1 (0.5%) case of agranulocytosis. Fifty-four cases (26.5%) had impaired liver function.ConclusionGD is more common in female children and adolescents. Parents may ignore their children's hypermetabolic symptoms in the early stages of GD. Routine blood and liver function tests are recommended at initial diagnosis to exclude abnormal hemogram and liver function.

Agranulocytosis following intravenous immunoglobulin administration in a patient with Guillain-Barré Syndrome triggered by COVID-19: A case report

Neutropenia during recovery after coronavirus disease 2019 (COVID-19), as well as neutropenia after intravenous immunoglobulin (IVIG) administration are very rare hematological abnormalities. We report the first case of agranulocytosis following IVIG administration in patients with Guillain-Barre syndrome (GBS) triggered by COVID-19. A 62-year-old female patient was admitted to the Emergency Department due to progressive limb weakness and sensory disturbances that began two weeks before admission. Five weeks before admission she was treated for COVID-19 and has fully recovered. She was diagnosed with Guillain-Barre syndrome (GBS), and treatment with IVIG was started. Twenty hours after the first dose of IVIG, blood analysis showed neutropenia and thrombocytopenia, and after the fifth dose she developed agranulocytosis followed by mild increase in body temperature. Granulocyte colony-stimulating factor (G-CSF) was administered and after 12 hours the leukocyte lineage recovered. According to the previous findings, neutropenia after IVIG administration might be related to CD11b, and COVID-19 is associated with an increase in immature neutrophil populations in the later stages of the disease defined by their expression of CD11b. Meanwhile, some finding suggests that corticosteroid pretreatment prevent neutropenia after IVIG administration, which might be important because many patients with post-COVID GBS have been treated with corticosteroids for COVID-19.

Clozapine cessation

IntroductionApproximately 30% of individuals diagnosed with schizophrenia suffer from treatment-resistant or refractory schizophrenia. The gold standard for treatment is clozapine. However, a significant number of patients discontinue clozapine treatment and this carries a poor prognosis.ObjectivesThis study explores patients’ motives for cessation of clozapine therapy and its prevalence.MethodsA longitudinal, retrospective and descriptive study on a period of 20 years, at the psychiatry department A of the Razi hospital in Tunisia. Data was collected from the medical files of patients trated by clozapine using a pre-established sheet.ResultsThe studied sample included 64 patient records. Treatment with clozapine was stopped spontaneously or following a medical decision in 37 patients (57.8%). The total number of clozapine stops in these 37 patients was 70. Indeed, each one of these patients had stopped treatment at least once. Clozapine was discontinued by some patients in the study sample for poor compliance(45.9%), for adverse side effects of treatment (16.2%) and by treating physicians for poor response treatment (8.1%). Clozapine was discontinued by 11 patients for hematological adverse reactions, representing 27.9% of the total number of clozapine discontinuations. Withdrawal of clozapine was indicated in 2 cases of agranulocytosis(18.2%), in 2 cases of moderate neutropenia(18.2%), in 3 cases of eosinophilia (27.2%), in 3 cases of thrombocytopenia (27.2%) and in 1 case of severe anemia (9.2%).ConclusionsClozapine discontinuation was essentially caused by poor patients’ observation and hematological adverse reactions appearance.Future research should seek to further investigate clozapine cessation factors in order to better benefit from the medical virtues of this molecule.DisclosureNo significant relationships.

Time of onset of hematological side effects with Clozapine

IntroductionClozapine use is not deprived of serious complications that can condition treatment strategies, particularly hematological. Recognizing the time it takes for these effects to set, can therefore help to better screen their appearance, improving healthcare.ObjectivesTo study the time of onset of hematological adverse reactions in patients treated with Clozapine.MethodsA longitudinal, retrospective and descriptive study on a period of 20 years starting from the first of January 2000, at the psychiatry department A of the Razi hospital in Tunisia. This study was conducted on patients treated by Clozapine. The data was collected from patients’ medical files using a pre-established sheet.ResultsThe studied sample included 64 patient. Hematological disorders were found in 21 patients (32.8%). The mean time of onset of hematological adverse reactions was 119.71±126.56 days. Indeed, some patients had presented more than one hematological disorder and this at different times. Mild to moderate neutropenia had a mean time of onset of 502.57±908.32 days. The time of onset of eosinophilia was 937.75±1725.87 days, 297.67 ± 444.93 days for thrombocytopenia, 741±1268.85 days for leukopenia, 69.25 ± 48.19 days for hyperleukocytosis and 183. 33±231.80 days for anemia. Two cases of agranulocytosis were noted: one case occurred 10 years and three months from treatment beginning and the second case occurred after 7 months of treatment onset.ConclusionsThe time of onset of hematological side effects with clozapine varies widely and cannot be predicted with precision. Early, more frequent and regular surveillance is therefore necessary in this population.DisclosureNo significant relationships.