Levamisole Induced Agranulocytosis in a Child with Steroid Dependent Nephrotic Syndrome: A Case Report.

ABSTRACT: Levamisole has been used as an effective immunomodulator. Levamisole has been used for nephrotic syndrome due to its immunostimulant, immunomodulating, and steroid-sparing effects. Common adverse effects of levamisole are gastrointestinal symptoms (nausea, abdominal cramps), and pyrexia. However, agranulocytosis or pancytopenia is also a rare but life-threatening complication of levamisole. This is a case report of a 5-year-old girl who had steroid-dependent nephrotic syndrome for which she was started on levamisole as per her weight, following which she had falling total leukocyte count levels on every visit. Thus, this case report emphasizes identifying this rare side effect and its management.

Clozapine monitoring requirements: is it time for an update?

Oloyede and colleagues advocate for updating haematological monitoring requirements for clozapine, arguing that current protocols overestimate the risk of clozapine-induced agranulocytosis. Their research suggests that stringent monitoring may unnecessarily limit access to clozapine, a crucial treatment for resistant schizophrenia. The editorial supports calls for international consensus to carefully weigh the pros and cons of relaxing monitoring guidelines while ensuring comprehensive care for patients.

Assessing potential risk factors for metamizole-induced leukopenia.

Background: Metamizole is a non-opioid analgesic agent that can rarely cause agranulocytosis, a severe form of leukopenia. Objectives: The aim of this study was to assess previously identified potential risk factors for the development of metamizole-induced leukopenia. Design: A retrospective, observational, matched case-control study was performed in a single-center setting. Methods: Patients who developed leukopenia in the setting of metamizole therapy were included as cases and matched 1:3 on the basis of age and sex to control patients who did not develop leukopenia when treated with metamizole. The data were obtained from the medical records of patients hospitalized at Cantonal Hospital Baselland between 2015 and 2020. Univariate and multivariate analyses were performed. Results: Eighty-six cases and 258 matched controls aged between 18 and 102 years were included. Fifty-seven percent were female. Previous leukopenic episodes (odds ratio (OR): 4.02, 95% CI: 1.95-8.28, p < 0.001) and a history of penicillin allergy (OR: 2.49, 95% CI: 1.03-6.03, p = 0.044) were found to be independent risk factors for metamizole-induced leukopenia. Conclusion: A history of previous leukopenic episodes and a history of penicillin allergy were confirmed as risk factors for metamizole-induced leukopenia. In our opinion, metamizole should be avoided in patients with these risk factors.

METHOD: We compared hospitalized patients treated with metamizole who developed leukopenia, with similar hospitalized patients who did not develop this side effect. RESULTS: It was observed that patients were more likely to develop leukopenia under metamizole therapy if they: - had previous episodes of leukopenia - were under cytostatic/immunosuppressive therapy (for example drugs used to treat cancer or autoimmune conditions) - had a history of penicillin allergy. CONCLUSION: These findings will help in identifying people who are at risk of developing this serious side effect, so that they can be given a medication for pain or fever that suits them better.

Assessing potential risk factors for metamizole-induced leukopenia Background: Metamizole is a medication used to treat pain and fever. It carries a risk of developing the side effect of a low white blood cell count (leukopenia). Researchers have identified certain risk factors which predispose some, but not all, people to develop this side effect. We undertook this study to examine these risk factors in more detail.

Deferasirox, an iron chelator, impacts myeloid differentiation by modulating NF-kB activity via mitochondrial ROS.

The iron chelator deferasirox (DFX) is effective in the treatment of iron overload. In certain patients with myelodysplastic syndrome, DFX can also provide a dramatic therapeutic benefit, improving red blood cell production and decreasing transfusion requirements. Nuclear Factor-kappa B (NF-kB) signalling has been implicated as a potential mechanism behind this phenomenon, with studies focusing on the effect of DFX on haematopoietic progenitors. Here, we examine the phenotypic and transcriptional effects of DFX throughout myeloid cell maturation in both murine and human model systems. The effect of DFX depends on the stage of differentiation, with effects on mitochondrial reactive oxygen species (ROS) production and NF-kB pathway regulation that vary between progenitors and neutrophils. DFX triggers a greater increase in mitochondrial ROS production in neutrophils and this phenomenon is mitigated when cells are cultured in hypoxic conditions. Single-cell transcriptomic profiling revealed that DFX decreases the expression of NF-kB and MYC (c-Myc) targets in progenitors and decreases the expression of PU.1 (SPI1) gene targets in neutrophils. Together, these data suggest a role of DFX in impairing terminal maturation of band neutrophils.

A Case of Amiodarone-Induced Thyrotoxicosis Presenting With Methimazole-Induced Agranulocytosis.

Amiodarone is a class III anti-arrhythmic drug found to be effective in treating multiple life-threatening arrhythmias, including paroxysmal atrial fibrillation. Despite its effectiveness, amiodarone has been found to result in thyroid dysfunction. Amiodarone-induced thyrotoxicosis (AIT) is classified as type 1, which often develops in those with autoimmune hyperthyroid conditions, or type 2, which occurs because of destructive thyroiditis in an apparently normal thyroid. Differentiating between both types often poses a clinical and therapeutic dilemma, as AIT 1 is treated with thionamides, whereas AIT 2 requires steroids for treatment. We present a case of a patient with AIT who was treated empirically for both subtypes with methimazole and prednisone without clinical improvement. Methimazole was later stopped due to concern for agranulocytosis, and the patient was then treated with cholestyramine, metoprolol, and prednisone. Given persistent thyrotoxicosis, the decision was made to proceed with surgical intervention. The patient underwent a successful total thyroidectomy without complications. The patient's condition clinically improved post-surgery and was discharged home on post-operative day 2 in stable condition. Prednisone was tapered over two weeks, and he was started on a weight-based dose of levothyroxine. He continues to follow up in our clinic for postoperative hypothyroidism and is clinically and biochemically euthyroid.

Methimazole-Induced Pancytopenia in a Patient with Graves' Disease: A Case Report and Literature Review.

INTRODUCTION: Methimazole is an antithyroid drug known to cause hematological toxicity, including agranulocytosis and, very rarely, pancytopenia. We herein present a case of a patient with Graves' Disease (GD) who developed methimazole-induced pancytopenia. CASE REPORT: A 53-year-old Peruvian woman with GD, initially treated with methimazole 20 mg BID, experienced odynophagia, fever, and malaise after 37 days of treatment. The initial diagnosis was agranulocytosis, leading to the discontinuation of methimazole and initiation of antibiotics. Due to persistent neutropenia, a Granulocyte Colony-stimulating Factor (G-CSF) was administered. Eight days later, she developed pancytopenia and was managed with hematopoietic agents and platelet transfusions. The patient recovered with normalization of the blood count, eliminating the need for Bone Marrow (BM) examination. Radioiodine therapy was chosen as the definitive treatment, resulting in hypothyroidism. Currently, the patient is thyroidal and hematologically stable. CONCLUSION: Methimazole-induced pancytopenia is a rare and serious complication; however, with appropriate treatment, complete recovery can be achieved.

Predicting non-chemotherapy drug-induced agranulocytosis toxicity through ensemble machine learning approaches.

Agranulocytosis, induced by non-chemotherapy drugs, is a serious medical condition that presents a formidable challenge in predictive toxicology due to its idiosyncratic nature and complex mechanisms. In this study, we assembled a dataset of 759 compounds and applied a rigorous feature selection process prior to employing ensemble machine learning classifiers to forecast non-chemotherapy drug-induced agranulocytosis (NCDIA) toxicity. The balanced bagging classifier combined with a gradient boosting decision tree (BBC + GBDT), utilizing the combined descriptor set of DS and RDKit comprising 237 features, emerged as the top-performing model, with an external validation AUC of 0.9164, ACC of 83.55%, and MCC of 0.6095. The model's predictive reliability was further substantiated by an applicability domain analysis. Feature importance, assessed through permutation importance within the BBC + GBDT model, highlighted key molecular properties that significantly influence NCDIA toxicity. Additionally, 16 structural alerts identified by SARpy software further revealed potential molecular signatures associated with toxicity, enriching our understanding of the underlying mechanisms. We also applied the constructed models to assess the NCDIA toxicity of novel drugs approved by FDA. This study advances predictive toxicology by providing a framework to assess and mitigate agranulocytosis risks, ensuring the safety of pharmaceutical development and facilitating post-market surveillance of new drugs.

Severe neutropenia unrelated to clozapine in patients receiving clozapine.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Case report: A rare case of anti-PD-1 sintilimab-induced agranulocytosis/severe neutropenia in non-small cell lung cancer and literature review.

Immune checkpoint inhibitors (ICIs) demonstrate unique advantages in the treatment of lung cancer and are widely used in the era of immunotherapy. However, ICIs can cause adverse reactions. Hematological toxicities induced by immunotherapy are relatively rare. Agranulocytosis, a rare hematologic adverse event associated with immune checkpoint inhibitors, has received limited attention in terms of treatment and patient demographics. Herein, we report the case of a 68-year-old male with non-small cell lung cancer(NSCLC) who received two cycles of programmed cell death-1 (PD-1) antibody sintilimab immunotherapy combined with albumin-bound paclitaxel and carboplatin chemotherapy and one cycle of sintilimab monotherapy. He was diagnosed with grade 4 neutropenia and sepsis (with symptoms of fever and chills) after the first two cycles of treatment. Teicoplanin was promptly initiated as antimicrobial therapy. The patient presented with sudden high fever and developed agranulocytosis on the day of the third cycle of treatment initiation, characterized by an absolute neutrophil count of 0.0×109/L. The patient was treated with granulocyte colony-stimulating factor but did not show improvement. He was then treated with corticosteroids, and absolute neutrophil counts gradually returned to normal levels. To the best of our knowledge, this is the first reported case of sintilimab-induced agranulocytosis in a patient with NSCLC. Sintilimab-induced severe neutropenia or agranulocytosis is a rare side effect that should be distinguished from chemotherapy-induced neutropenia and treated promptly with appropriate therapies; otherwise, the condition may worsen.

Genetic susceptibility to breast cancer increases the risk of neutropenia and agranulocytosis: insights from Mendelian randomization.

PURPOSE: The causal relationship between breast cancer and its estrogen receptor (ER) subtypes and neutropenia and agranulocytosis is unclear. METHODS: In two-sample Mendelian randomization (MR), we used inverse variance weighting (IVW), Bayesian weighted MR (BWMR), MR-Egger, weighted median, simple mode, and weighted mode methods to analyze causality for ER-positive breast cancer, ER-negative breast cancer, overall breast cancer, and drug-induced neutropenia and agranulocytosis. To validate the results, we performed the analysis again using GWAS data on neutropenia from different databases. In multivariable MR (MVMR), we assessed the independent effects of ER-positive and ER-negative breast cancer on causality. RESULTS: Two-sample MR analysis showed a causal relationship between ER-positive breast cancer (IVW odds ratio (OR) = 1.319, P = 7.580 × 10-10), ER-negative breast cancer (OR = 1.285, P = 1.263 × 10-4), overall breast cancer (OR = 1.418, P = 2.123 × 10-13), and drug-induced neutropenia and a causal relationship between ER-positive breast cancer (OR = 1.349, P = 1.402 × 10-7), ER-negative breast cancer (OR = 1.235, P = 7.615 × 10-3), overall breast cancer (OR = 1.429, P = 9.111 × 10-10), and neutropenia. Similarly, ER-positive breast cancer (OR = 1.213, P = 5.350 × 10-8), ER-negative breast cancer (OR = 1.179, P = 1.300 × 10-3), and overall breast cancer (OR = 1.275, P = 8.642 × 10-11) also had a causal relationship with agranulocytosis. MVMR analysis showed that ER-positive breast cancer remained causally associated with drug-induced neutropenia (OR = 1.233, P = 4.188 × 10-4), neutropenia (OR = 1.283, P = 6.363 × 10-4), and agranulocytosis (OR = 1.142, P = 4.549 × 10-3). Heterogeneity analysis and pleiotropy test showed that our results were reliable. CONCLUSION: Our study provides genetic evidence for a causal association between breast cancer and its estrogen receptor subtypes and neutropenia. In clinical practice, in addition to focusing on therapeutic factors, additional attention should be given to breast cancer patients to avoid severe neutropenia.

Evaluating Reduced Blood Monitoring Frequency and the Detection of Hematological Abnormalities in Clozapine-Treated Patients With Schizophrenia: A Chart Review Study From the COVID-19 Pandemic.

BACKGROUND AND HYPOTHESIS: In response to Health Canada's March 2020 directive, patients on clozapine for over 12 months were allowed to extend hematological testing intervals from 4 to 8 weeks during the COVID-19 pandemic. We hypothesized that this change would not affect the timely detection of hematological abnormalities in patients with severe mental illness. STUDY DESIGN: A chart review was conducted of patients at the Royal Ottawa who were prescribed clozapine from March 2019 to March 2021. We analyzed clinical and hematological data from electronic health records and Clozaril Support and Assistance Network database to compare occurrences of hematological abnormalities [leukopenia (white blood cell count <3.5 × 109/L) and agranulocytosis (absolute neutrophil count <0.5 × 109/L)] from March 17, 2020 to March 16, 2021, between standard and extended monitoring protocols using binomial logistic and zero-inflated negative binomial regressions. STUDY RESULTS: Of 621 patients, 196 were on extended blood monitoring, and 425 followed standard blood monitoring. Clozapine dose did not differ between groups (standard: 370 ±â€…201 mg; extended: 352 ±â€…172 mg; P = .14, ds = 0.10). Clozapine treatment duration up to March 2021 was 12.6 ±â€…8.3 years, with the extended group (10 ±â€…7.9 years) having a significantly (P < .01, ds = 0.50) shorter duration than the standard (14 ±â€…8.2 years). Extended monitoring did not significantly impact likelihood of detecting hematological abnormalities (OR = 0.83, 95% CI [0.58,1.41], P = .55) after controlling for age, sex, total bloodwork, and other psychotropics associated with neutrophil counts (ie, valproate, olanzapine). No patient on the extended regimen developed agranulocytosis. CONCLUSIONS: Reducing blood monitoring frequency in patients on clozapine for more than 12 months did not compromise detection of hematological abnormalities.

Treatment of Tislelizumab-Induced Toxic Epidermal Necrolysis and Agranulocytosis: A Case Report and Literature Review.

BACKGROUND: Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become crucial in NSCLC treatment, significantly enhancing survival for some. However, side effects, like skin reactions and hematotoxicity, limit their use, with drug-induced TEN and immunotherapy-induced agranulocytosis as severe adverse effects. CASE PRESENTATION: Herein, we have reported the case of a 75-year-old male diagnosed with metastatic Lung Squamous cell Carcinoma (LUSC) in the left lung. He received first-line treatment with one cycle of tislelizumab in combination with nab-paclitaxel and carboplatin, after which he developed Toxic Epidermal Necrolysis (TEN) and granulocytopenia. To address these two serious immune-related Adverse Events (irAEs), the patient was administered methylprednisolone in combination with gamma globulin for TEN and dexamethasone in combination with G-CSF for agranulocytosis. Antibiotics were also administered according to the patient's medication regimen. After treatment, the patient recovered and was discharged from the hospital. It was also noted that the lung tumor condition improved. CONCLUSION: Effective management of severe immune-related side effects from tislelizumab, including TEN and agranulocytosis, can be partly achieved through steroids, gamma globulin, GCSF, and antibiotics. This strategy not only alleviates these adverse effects, but also potentially improves tumor conditions, highlighting the crucial role of vigilant monitoring and management in immunotherapy.

Decoding Clozapine-Induced Agranulocytosis: Unraveling Interactions and Mitigation Strategies.

Agranulocytosis represents a severe complication associated with the administration of clozapine. Clozapine is an antipsychotic medication that has demonstrated substantial efficacy in remediating refractory schizophrenia and various other psychiatric disorders. Nonetheless, it is crucial to monitor patients for neutropenia regularly during clozapine therapy. Therefore, this article aimed to delve into the prevalence of agranulocytosis during clozapine treatment by scrutinizing the extant literature to discern trends and correlations. This review endeavored to explore factors such as drug interactions, dose-related factors, duration of treatment, and genetic predispositions that could potentially influence the likelihood of patients developing agranulocytosis while undergoing clozapine therapy. Moreover, this review enunciates the ramifications of agranulocytosis on both patients and healthcare providers and meticulously evaluates the strategies to mitigate this risk and ensure optimal patient outcomes.

Risk of agranulocytosis with metamizole in comparison with alternative medications based on health records in Spain.

PURPOSE: We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005-2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before). RESULTS: The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37-40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/107 person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92-26.99] and 4.40 [0.90-21.57] versus NSAID, and 3.31 [1.17-9.34] and 2.45 [0.68-8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57-5.65] versus NSAID. CONCLUSIONS: Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded.

Understanding clozapine-related blood dyscrasias. Developments, genetics, ethnicity and disparity: it's a CIN.

Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.

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.

Time for a change to clozapine haematological monitoring.

OBJECTIVES: This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA). The paper appraises the extant literature on mandatory clozapine haematological monitoring. CONCLUSION: Contemporary Australian protocols for clozapine haematological monitoring are not consistent with the current evidence base. CIN and CIA are rare occurrences, and the associated risk of death is low. Potential modifications to existing guidelines include changing neutrophil thresholds for patients with benign ethnic neutropenia and reducing the frequency or removing haematological monitoring after two years of clozapine treatment.

Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10.

Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated the preventive and reversal effects of taurine and coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, against CPZ-induced hematological impairments in male rats. In the preventive study, rats received oral saline (10 ml/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or in combination for 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. In the reversal protocol, rats had CPZ repeatedly for 56 days before taurine and COQ-10 treatments or their combination from days 29-56. Rats were also given taurine (150 mg/kg/day), and COQ-10 (10 mg/kg/day) alone for 56 days. Serums were extracted and assayed for hematological, with oxidative and inflammatory markers. CPZ induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume and hemoglobin, neutrophil, and lymphocyte, which were prevented and reversed by taurine and COQ-10, or their combination. Taurine and COQ-10 improved mean corpuscular volume, hemoglobin concentration, with increased erythropoietin levels relative to CPZ groups. CPZ-induced increased malondialdehyde, tumor necrosis factor-alpha and interleukin-6 levels with decreased interleukin-10, glutathione, and superoxide-dismutase were prevented and reversed by taurine and COQ-10 in comparison with CPZ groups. Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

Agranulocytosis Associated With Psychiatric Polypharmacy: Lessons Learned From a Clinical Case.

Psychiatric polypharmacy involves the use of two or more psychotropic medications to manage a mental and emotional condition. The prevalence of psychotropic polypharmacy has been increasing since the 1990s and has been attributed to the rise in multiple psychiatric conditions presenting in one patient. However, as the prevalence of polypharmacy increases to maximize therapeutic advantages, so does the adverse effect profile of those drugs used in combination, leading to very life-threatening effects such as agranulocytosis. Thus, we report a case of agranulocytosis secondary to polypharmacy in a patient with a history of multiple complex psychiatric conditions.  The patient is a 20-year-old female with a past medical history of major depressive disorder, borderline personality disorder, post-traumatic stress disorder, anxiety disorder, hypothyroidism, and ulcerative colitis. Her psychiatric conditions were managed with multiple medications including chlorpromazine, and clozapine was recently added a month prior to admission. Upon admission, the patient was hemodynamically stable and febrile, with complaints of generalized body aches and myalgia. Laboratory results showed profound leukopenia with a white blood cell count of 1.0x103/uL and a neutrophil number of 0.02x103/uL. The patient was admitted to the hospital for neutropenic sepsis and was aggressively treated with intravenous antibiotics. Her clozapine and chlorpromazine were discontinued. In this report, we discuss the association between chlorpromazine and clozapine use and agranulocytosis, emphasizing the importance of regular monitoring and heightened awareness for patients on these medications. This case also underscores the necessity for cautious polypharmacy medication management in individuals with complex psychiatric conditions, highlighting the potential life-threatening consequences of polypharmacy in this population.

Gingival Necrosis Related to Sepsis-Induced Agranulocytosis Due to Pseudomonas aeruginosa Bacteraemia: A Case Report.

Background: There have been no reports of sepsis-induced agranulocytosis causing gingival necrosis in otherwise medically healthy patients to the authors' best knowledge. Even though there are several case reports of gingival necrosis secondary to medication-induced agranulocytosis, they have not systematically described the natural progression of agranulocytosis-related gingival necrosis. Methods: This paper presents a case report of a 29-year-old female Indian patient with generalised gingival necrosis and constitutive signs of intermittent fever, nausea, and vomiting. She also complained of abdominal pains. Blood counts showed agranulocytosis, and the patient was admitted for a workup of the underlying cause. Parenteral broad-spectrum antibiotics were administered, which brought about clinical resolution. Results: Her gingival necrosis was attributed to sepsis-induced agranulocytosis triggered by Pseudomonas aeruginosa bacteraemia, and upon clinical recovery, spontaneous exfoliation left behind exposed bone. Secondary healing over the exposed alveolar bone was noted after a year-long follow-up, albeit with some residual gingival recession. Conclusions: Oral manifestations of gingival necrosis, when present with concomitant constitutive symptoms, could indicate a serious underlying systemic condition that could be potentially life-threatening if left untreated. Dentists should be cognizant of this possibility so that timely intervention is not delayed.