Agranulocytosis In Patients Research Articles

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.

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.

Physicians' and Patients' Perceptions and Practices Concerning Antithyroid Drug-Induced Agranulocytosis

Abstract Objectives We aimed to ascertain physicians' attitudes and practices and evaluate patients' knowledge of antithyroid drugs (ATDs). Also, we would like to review the quality of patients' information on the Internet (in Arabic) concerning ATDs' including agranulocytosis. Methods A mixed methods study design was employed, including an online physician questionnaire, structured interviews of patients on ATDs, and evaluation on web sites containing patients' information in Arabic. Results Most physicians (82.6%) thought the frequency of agranulocytosis in patients receiving antithyroid medications is 1 to 5 per 1,000 per annum. Nearly 72% of the participants reported educating their patients about the risk of agranulocytosis when they receive ATDs regularly verbally only. Most physicians thought patients should be warned about sore throat and fever. More participants would measure a white blood cell (WBC) count only if a patient developed suggestive symptoms (57.0%) than those who do it routinely (43.0%). If a patient receiving ATDs develops suspicious symptoms, participants thought that the most efficient way to deal with this is to attend the nearest hospital emergency department (37.2%). Less thought they can go to any facility with a laboratory that can do WBC count (29.8%) or contact their usual endocrine clinic (24.4%). Nearly half of the patients (49%) were aware of the side effects of ATDs, but only 17 respondents (17.3%) identified one or both of the two most typical symptoms of agranulocytosis. The quality of the information received was evaluated as “not good at all” or “poor” by 19.2%. Over two-thirds (69.7%) of participants thought the amount of information was about right. Most participants (72.5%) preferred receiving information on side effects during consultations with their physicians. Since starting ATDs, 37.0% of patients have experienced different symptoms suggestive of agranulocytosis in various combinations. However, only one-third (12/37) had an urgent blood count. A review of 190 selected Arabic patient information Internet sites revealed a significant variation in patient advice. Six percent 11/190 (5.8%) of the sites can be considered good. Conclusions The findings of suboptimal and inconsistent perceptions and practices of physicians and patients put patients with ATD in the Middle East at increased risk and call for more action from professional and patient advocacy groups.

Diamond–Blackfan anaemia with iron overload: A serious issue

Transfusion-dependent Diamond-Blackfan anaemia (DBA) patients rapidly develop iron overload and frequently experience cardiac complications. The report by Lecornec and colleagues offers useful details on indications and the management of deferiprone, a highly efficient chelator in removing excess cardiac iron but associated with a high risk of agranulocytosis in DBA patients. Commentary on: Lecornec et al. Agranulocytosis in patients with Diamond-Blackfan anaemia (DBA) treated with deferiprone for post-transfusion iron overload: A retrospective study of the French DBA cohort. British Journal of Haematology 2022;199:285-288.

Value of the Diagnostic-Driven Therapy with Voriconazole in Patients with Hematological Disorders Complicated by Invasive Fungal Disease

To explore the value of the diagnostic-driven therapy with voriconazole in patients with hematological disorders complicated by invasive fungal disease (IFD). A total of 111 patients with hematological disorders complicated by IFD, treated with voriconazole in the hematology department of the General Hospital of South Theatre Command from July 2019 to July 2020, were retrospectively analyzed to compare the differences between the empirical therapy and the diagnostic-driven therapy on the treatment time of voriconazole, hospitalization days and antifungal efficacy. SPSS 23.0 was used for statistical analysis of data. Compared with the diagnostic-driven therapy group, the empirical therapy group had more IFD high-risk patients, including a higher proportion of agranulocytosis patients (95.2% vs 69.5%, P=0.003). However, there were no significant differences on the treatment time of voriconazole, hospitalization days and antifungal efficacy of voriconazole between the two groups. Using diagnostic-driven therapy in relatively IFD low-risk patients can obtain similar therapeutic outcomes and prognosis as empirical therapy in high-risk patients. Either of two strategies can be used in clinical practice according to the individual conditions of patients.

Analysis of Agranulocytosis Time and Its Influencing Factors in Patients with Hematological Malignancies Treated with rhIL-11 combined rhG-CSF

To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors. The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis. The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P＜0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4－6 and ≥7, patients with total chemotherapy cycle of 1－3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline <1.0×109/L, (1.0－1.9)×109/L and (2.0－3.9)×109/L, patients with WBC baseline ≥4.0×109/L had the shortest duration of agranulocytosis, which was 4.50±2.56 d. Multiple linear regression analysis showed that chemotherapy cycle, different fever after administration of rhG-CSF and rhIL-11, diagnosis of ALL and NHL, and WBC baseline level before administration of rhG-CSF and rhIL-11 were the influencing factors of the duration of agranulocytosis (P＜0.001). The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.

Low-Dose Clozapine-Induced Agranulocytosis in Patients with Movement Disorders-Retrospective Study from India.

Low-Dose Clozapine-Induced Agranulocytosis in Patients with Movement Disorders-Retrospective Study from India.

Emergency Combination of Four Drugs for Bloodstream Infection Caused by Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients with Hematologic Malignancies after Hematopoietic Stem Cell Transplantation.

Bloodstream infection (BSI) caused by multidrug-resistant (MDR) bacteria or extensively drug-resistant (XDR) bacteria is a global threat. However, an effective treatment regimen is still controversial and inadequate due to the rapid deterioration caused by the bacteria. In immunocompromised and neutropenic patients, MDR-BSI is an emergency, which causes treatment-related mortality. In this study, four agranulocytosis patients with hematologic malignancies after HSCT receiving treatment for carbapenem-resistant Enterobacteriaceae- (CRE-) BSI were included. Conventional treatment using two to three combined antibiotics was administered in the first and second patients. Combination treatment using four drugs, polymyxin B, high-dose tigecycline, fosfomycin, and double-dose carbapenem, was administered in the third and fourth patients. None of the patients receiving conventional treatment survived. Both patients receiving combination treatment using four drugs survived. Therefore, four-drug combination therapy may be needed in CRE-BSI patients who experienced severe agranulocytosis after HSCT. The efficacy of the four-drug combination treatment for CRE-BSI patients as well as the adverse effects need to be further studied.

Clinical Features of Nosocomial Infections in Agranulocytosis Patients with Hematological Malignancies and Analysis of Risk Factors

To explore the clinical features and risk factors for nosocomial infections in agranulocytosis patients with hematological malignancies so as to provide basis for clinical prevention and treatment of nosocomial infections. The clinical data of 725 patients with agranulocytosis in the First Hospital of Lanzhou University from May 2015 to May 2018 were retrospectively analyzed, including sex, age, primary disease, treatment stage, agranulocytosis degree, agranulocytosis duration, nosocomial infection, infectous site, average length of stay and average days of infection. Univariate analysis (Chi-square test) and multivariate analysis (non-conditional Logistic regression models) were used to analyze the risk factors of nosocomial infection. The most common sites of nosocomial infection in agranulocytosis patients with hematological maliguancies were upper respiratory tract, accounting for 24.0%, followed by lung (16.2%) and blood stream (13.8%). In disease composition, acute leukemia holded the first place, accounting for 82.1%, among which the acute myeloid leukemia had the highest infection rate, accounting for 73.3%, followed by acute lymphoblastic leukemia. The infection rates were 68.0% and 66.7% for multiple myeloma, 79.3% and 84.5% for acute leukemia at the initial induction and relapse stages, respectively. 184 pathogenic bacteria were isolated clinically, of which 126 were a Gram-negative bacteria, 23 were Gram-positive bacteria and 35 were fungi, accounting for 68.48%, 12.50% and 19.02%, respectively. It was found that age, primary disease, degree and duration of granulocyte deficiency, chemotherapy, glucocorticoid use and disease status all associated with nosocomial infection (P＜0.05). Multivariate unconditional logistic regression analysis showed that acute leukemia, absolute count of neutrophils＜0.2×109/L, chemotherapy and disease unremitting were the main risk factors of nosocomial infection. The patients with malignant hematological agranulocytosis are a high-risk population of nosocomial infection. Nosocomial infection rate is still high, especially in patients with acute leukemia who have received chemotherapy or without complete remission or neutrophil absolute count less than 0.2×109/L. Thus early intervention measures should be taken to reduce the incidence of nosocomial infection and mortality.

Combination of Four Drugs for Bloodstream Infection Caused By Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients after Hematopoietic Stem Cell Transplantation

Bloodstream infection (BSI) caused by multidrug‐resistant bacteria (MDRB) or extensively drug-resistant bacteria (XDRB) in immunocompromised and neutropenic patients after hematopoietic stem cell transplantation (HSCT) is a global threaten. However, effective treatment regimen is still controversial and inadequate due to the rapid deterioration, the horrific evolution of bacteria and high mortality that the mortality related to BSI caused by carbapenem-resistant Enterobacteriaceae (CRE) is 51% in adult neutropenic patients[1]. Here, we presented four cases that CRE was detected in blood of severe agranulocytosis patients undergoing HSCT. All patients ranged from 2 to 50 years old were diagnosed as hematologic disease. CREs were detected within 1 month from the date of engraftment. In case 1, a 6-year-old boy with high-risk B-cell acute lymphocyte leukaemia received halpo-HSCT after chimeric antigen receptor T-cell therapy and the 20th chemotherapy, ultimately, he died from acute graft versus host disease and BSI that tienam and tigecycline showed little effect though the MIC value of tigecycline was less than 0.5ug/ml. The second patient is a 25-year-old female who was diagnosed as hemophagocytic syndrome with recurrent fever and a salvage haploidentical transplantation combining with a unit of umbilical cord blood stem cells was performed. Finally, she died from BSI caused by CRE although a combination therapy using polymyxin B, tigecycline and doubled-dose Tienam was given, which subsequently was changed to another therapeutic regimen using a higher dose tigecycline and fosfomycin and polymyxin B in light of the resistance of tienam. Patients in case 3 and case 4 received a combination therapy with tigecycline, polymyxin B, fosfomycin, and Tienam intravenously. For the 29-month-old boy diagnosed as acute monocytic leukemia with high expression of WT1 and abnormal karyotype and treated with cord blood stem cell transplantation in case 3, the tigecycline was given with a dose of 2.4mg/kg at the first time, followed by doses of 1.2mg per dose every 12 hours, and a dose of 2.0mg/kg at the first time, followed by doses of 1.25mg/kg per dose every 12 hours of polymyxin B, 0.15g/kg per every 12 hours of fosfomycin, as well as 30mg/kg per dose every 6 hours of imipenem were administrated. For the 50-year-old woman with multiple myeloma receiving an autologous hematopoietic stem cell transplantation (auto-HSCT) in case 4, the dose of tigecycline was 100mg at the first time, followed by doses of 1.2mg per dose every 12 hours. Fosfomycin with the dose of 8.0g was used every 12 hours, and the dose of imipenem was1.0g per dose every 6 hours, also, polymyxin B was administrated with a dose of 2.0mg/kg at the first time, followed by doses of 1.25mg/kg per dose every 12 hours. Consequently, patients in case 3 and case 4 were survival. Therefore, a strong combination therapy, as well as the emergency of new drugs might be considered in immunocompromised and neutropenic ill patients with BSI caused by MDRB or XDRB. Disclosures No relevant conflicts of interest to declare.

Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis

ObjectiveDeferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS.MethodsWe present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone.ResultsTen patients were followed up for a mean period of 2.3 years (range 0.5–5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3–2.5) with mean neutrophil count of 0.4 (range 0.3–0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated.ConclusionsDeferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.

Comparison of G-CSF and non-G-CSF treatment of agranulocytosis in patients with hyperthyroidism: a meta-analysis

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

Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Some effective antithyroid drugs (ATDs) have been widely used for patients with Graves’ disease (GD) but are associated with ATD-induced agranulocytosis. We selected 29 ATD-induced agranulocytosis patients, 44 ATD-induced neutropenia patients, and 140 GD controls among the Chinese Han population who were recruited at the First Affiliated Hospital of Xi’an Jiao Tong University. We assessed their response to ATDs treatment by performing genotyping for a candidate gene association study of samples from patients receiving treatment. Human flavin-containing monooxygenase 3 (FMO3), which is the major hepatic enzyme involved in the production of N-oxide of trimethylamine, catalyzes the oxygenation of a variety of drug compounds. Six single SNP, genotype, haplotype (HAP), and association analyses of the FMO3 gene with ATD-induced agranulocytosis/neutropenia under different models (i.e., additive, dominant, and recessive models) were performed. Rs1736557, which caused an amino acid variation V257M, showed a strong association between ATD-induced agranulocytosis and GD controls after Bonferroni correction (p = 0.011, OR 2.301, 95% CI 1.201–4.409). The presence of HAP 3 (HAP3) in the FMO3 gene HAP was statistically associated with ATD-induced agranulocytosis (p = 0.038, permutation p value). Our findings indicate that genetic variations in the FMO3 gene are associated with the response to ATDs maintenance treatment in ATD-induced agranulocytosis patients of ­Chinese Han population.

Increased Risk of Antithyroid Drug Agranulocytosis Associated with Amiodarone-Induced Thyrotoxicosis: A Population-Based Cohort Study.

Agranulocytosis occurs in 0.2-0.5% of patients treated with the antithyroid drugs (ATDs) methimazole and propylthiouracil. The objectives of this study were to evaluate the risk of ATD-related agranulocytosis in patients with amiodarone-induced thyrotoxicosis (AIT), and to compare it with the agranulocytosis risk in patients with thyrotoxicosis due to other etiologies treated with ATDs. This was a retrospective cohort study. Participants were 14,781 adult patients with thyrotoxicosis, newly treated with an ATD between January 1, 2002, and December 31, 2015. Among them were 593 patients treated by ATDs due to AIT. The main outcome measures were incidence rates and crude and adjusted hazard ratios using univariate and multivariable Cox regression models for ATD-related agranulocytosis within one year of treatment initiation, in association with AIT. Agranulocytosis occurred in 28 (0.19%) of patients newly treated with methimazole or propylthiouracil during the first year of follow-up. Of these 28 patients, 8/593 (1.35%) were AIT patients and 20/14,188 (0.14%) were thyrotoxic patients that was not AIT related (p < 0.001). Incidence rates were 22 (9.47-43.36) cases/1000 person-years of follow-up in AIT, and 1.79 (1.09-2.76)/1000 person-years of follow-up in non-AIT thyrotoxicosis (p < 0.0001). In univariate Cox regression analysis, risk for ATD agranulocytosis associated with AIT was 9.71 (4.28-22.05) compared to the risk in non-AIT thyrotoxicosis. In a multivariable model, adjusting for age, sex, body mass index, smoking history, year of cohort entry, diabetes mellitus, hypertension, renal failure, beta blockers, calcium channel blockers, anti-aggregants, and dose of ATDs, the risk associated with AIT was 5.70 (2.14-15.21). In a model adjusted for a propensity score to receive amiodarone, risk for ATD agranulocytosis associated with AIT was 6.32 (1.22-32.70). ATD use is associated with a higher risk for agranulocytosis in patients with AIT.

Etiologic analysis of Chinese patients with agranulocytosis and hematopathies infected with resistant bacteria: Antibacterial effect of tigecycline

Purpose : To assess the etiologic characteristics of resistant bacterial infections occurring in agranulocytosis patients with hematopathies, and to determine the effect of tigecycline (TGC). Methods : After ineffective treatment with carbapenem, all of the patients were divided into the following three groups: TGC alone (15 cases); TGC as initial treatment, followed by a combination with other antibiotics (40 cases); and TGC in combination with other antibiotics from the start of treatment (71 cases). Results : Among the 126 patients, 108 had fevers (85.71 %). The most common infection site was lung, accounting for 71.43 % of all infections. A total of 52 pathogens were isolated from 126 hospitalized patients, including 38 Gram-negative bacteria (70.37 %), 14 Gram-positive bacteria (25.93 %), and 2 fungi (3.70 %). TGC treatment efficacy was 50.79 %. There were no statistically significant differences between the three treatment groups (p = 0.473). Adverse drug reaction was nausea and vomiting (14.29 %), nausea without vomiting (11.90 %), diarrhea (6.35 %), and generalized skin rash with itching (3.17 %). Conclusion : TGC is effective in treating neutropenic patients with hematopathies who are infected with resistant bacteria. The side effects of TGC are few; thus, TGC is safe and generally well-tolerated. Keywords : Tigecycline, Agranulocytosis, Resistant bacteria, Hematopathy, Neutropenic patients

Association of HLA-B∗38:02 with Antithyroid Drug-Induced Agranulocytosis in Kinh Vietnamese Patients.

Background HLA-B∗38:02 has been shown to be associated with antithyroid drug-induced agranulocytosis in Asian patients. Methods HLA-B∗38:02 was analyzed by sequence-based typing in 21 patients who developed antithyroid drug-induced agranulocytosis and in 81 controls. Results Frequency of HLA-B∗38:02 was 52.4% in agranulocytosis patients compared to 3.7% in controls (OR = 28.6, 95% CI = 6.8–120.2). Conclusions HLA-B∗38:02 is a significant risk factor for agranulocytosis in Kinh Vietnamese patients treated with antithyroid drug.

Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population.

Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1null (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1null was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study.

Characteristics of Antithyroid Drug-Induced Agranulocytosis in Patients with Hyperthyroidism: A Retrospective Analysis of 114 Cases in a Single Institution in China Involving 9690 Patients Referred for Radioiodine Treatment Over 15 Years.

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood. Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed. The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 ± 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 ± 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 ± 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13). This largest single-institution study in China shows that ATD-induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach.

Agranulocytosis in a patient with acute Parvovirus B19 infection: a case study

The definition of neutropenia is the reduction in the absolute number of neutrophils below 1.5×10&lt;sup&gt;9&lt;/sup&gt;. The chapter about acquired neutropenias affecting the adult population is of particular interest to the internist. PC, 75 years old man, was hospitalized because of fever, asthenia. In anamnesis: recent diagnosis of ulcerative pancolitis treated with mesalazine and corticosteroid therapy. During the hospitalization, to the fever resolution, we witnessed to a gradual reduction in the value of neutrophils leucocytes until the complete agranulocytosis. We set a therapy with granulocytes colony stimulating factors, and antifungal. The osteo-medullar biopsy confirmed a pure aplasia of the granulocyte marrow series without any evidence of cancer. The subsequent clinical development was favorable, with stable apyrexia and recovery of leucocytes count. Few days after, we received the positive response on the research of anti-Parvovirus B19 immunoglobulin M and in qualitative polymerase chain reaction. The patient was discharged with diagnosis &lt;em&gt;agranulocytosis in patient with acute infection of Parvovirus B19&lt;/em&gt;. Neutropenia associated with Parvovirus infection is not frequent and is related to the presence of hematological diseases or condition of immunosuppression. The peculiarity of the case described is the complete agranulocytosis found: in fact in literature, only rare cases are described. Patient gave his informed consent.

Management and prevention of agranulocytosis in patients receiving clozapine

Clozapine is an antipsychotic associated with superior efficacy compared to other atypical antipsychotics in the treatment of schizophrenia. However, clozapine use is limited due to its association with a rare but potentially fatal adverse effect, agranulocytosis. Patients receiving clozapine therapy require frequent monitoring of white blood cell (WBC) and absolute neutrophil counts (ANC). This article reviews the monitoring parameters for patients receiving clozapine therapy, and the management and prevention of clozapine-associated agranulocytosis.