Apalutamide-induced severe agranulocytosis: a case report / 中华泌尿外科杂志

Adverse reactions commonly associated with apalutamide include hot flashes, fatigue, joint pain, rash, hypertension, and anemia. Apalutamide-induced agranulocytosis is relatively rare. In this paper, we reported a case with metastatic hormone-sensitive prostate cancer who developed agranulocytosis after taking apalutamide for one month. The patient’s neutrophil count returned to normal with appropriate supportive therapy, and no significant decrease in neutrophil count was observed during 10 months of follow-up after discharge.

Methimazole-induced agranulocytosis and other hematologic damages: Bone marrow characteristics and literature review / 中华内分泌代谢杂志

Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.

Infección oral y cervicofacial por agranulocitosis secundario debido al tratamiento con medicación antitiroidea: Reporte de Caso / Oral and Cervicofacial Infection Secondary to Agranulocytosis Caused by Antithyroid Medication: A Case Report

RESUMEN La agranulocitosis es el recuento bajo de glóbulos blancos (neutrófilos), que puede ser inducida por tratamientos con algunos medicamentos como los antitiroideos, que ocasionan manifestaciones orales como úlceras o necrosis gingival difusa. Se presenta el caso de una paciente mujer de 26 años, con antecedente de hipertiroidismo, quien acude a emergencia del Hospital Nacional Alberto Sabogal Sologuren por presentar tumefacción en la hemicara izquierda, asociada a disfagia, múltiples lesiones ulceradas en mucosa oral, con compromiso de tejido óseo, fiebre y malestar general. Luego de los exámenes auxiliares, se categoriza como una infección oral y cervicofacial por agranulocitosis debido al tratamiento con el metimazol. La literatura mundial reporta casos de agranulocitosis como efecto adverso del consumo de drogas antitiroideas, con reporte de manifestaciones orales; sin embargo, pocos casos evidencian compromiso cervical. Por lo cual se presenta este caso poco usual desde su diagnóstico hasta el tratamiento.

ABSTRACT Agranulocytosis refers to a low white blood cell count, specifically neutrophils, which can be caused by certain medications such as antithyroid drugs (ATD). This condition can result in oral manifestations, including diffuse gingival ulceration or necrosis. We present the case of a 26-year-old female patient with a history of hyperthyroidism who came to the emergency department of Alberto Sabogal Sologuren National Hospital with swelling on the left side of her face, accompanied by dysphagia, multiple ulcerated lesions in the oral mucosa involving bone tissue, as well as fever and general malaise. After conducting additional tests, the patient was diagnosed with oral and cervicofacial infection secondary to agranulocytosis caused by methimazole treatment. While the global literature reports cases of agranulocytosis as an adverse effect of antithyroid medication, with documented oral manifestations, only a few cases demonstrate cervical involvement. Therefore, we present this uncommon case from diagnosis to treatment.

Agranulocitosis secundaria a uso de vancomicina en pediatría. reporte de caso / Agranulocytosis secondary to vancomycin use in pediatrics. Case report

La vancomicina es un antibiótico de uso común en pacientes hospitalizados. Se han descrito múltiples efectos adversos relacionados a este fármaco, de los cuales la agranulocitosis es una entidad poco frecuente pero potencial mente grave. Este caso muestra una consecuencia médica secundaria al uso prolongado de este antibiótico, generando una neutropenia profunda posterior a 24 días de tratamiento, presentándose clínicamente con un pico febril aislado. Se asume que esta situación es consecuencia de una respuesta inmunológica inadecuada del huésped, por lo que la suspensión del agente etiológico es la clave del tratamiento. Existen pocos reportes de estos casos en la población pediátrica y debe considerarse un efecto secundario que requiere vigilancia estrecha para evitar repercusiones clínicas.

Vancomycin is a commonly used antibiotic in hospitalized patients. Multiple adverse effects related to this drug have been described, of which agranulocytosis is a rare but potentially serious entity. This case shows a medical consequence secondary to the prolonged use of this antibiotic, generating profound neutropenia after 24 days of treatment, presenting clinically with an isolated feverish peak. It is assumed that this situation is the consequence of an inadequate immunological response of the host, for which reason the suspension of the etiological agent is the key to treatment. There are few reports of these effects in the pediatric population and should be considered a side effect that requires close monitoring to avoid clinical repercussions.

Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.@*METHODS@#The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.@*RESULTS@#Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.@*CONCLUSION@#The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

Application value of metagenomic next-generation sequencing for pathogen detection in childhood agranulocytosis with fever / 中国当代儿科杂志

OBJECTIVES@#To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever.@*METHODS@#A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups.@*RESULTS@#For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-β-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged.@*CONCLUSIONS@#The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.

Apheresis granulocyte collection and transfusion efficacy / 中国输血杂志

【Objective】 To analyze the safety of apheresis granulocyte(AG) collection from blood donors mobilized by G-CSF and apheresis granulocyte transfusion efficacy in patients. 【Methods】 The blood routine results, collection process and follow-up of blood donors mobilized by G-CSF before and after AG collection were collected to analyze the safety of AG collection, and the blood routine results, clinical symptom improvement and treatment outcome of patients before and after AG transfusion were collected to analyze the transfusion efficacy. 【Results】 A total of 27 blood donors donated 29 U AG, with collection time at (229±20)min, circulating blood volume at (9 890±1 107)mL, and the dosage of anticoagulant at (1 002±97)mL.Two blood donors had adverse reactions to blood donation, and the AG collection was carried out after treatment.After G-CSF mobilization, WBC increased significantly from (5.61±1.06) ×109/L to (22.85±5.23) ×109/L, while RBC, Hb, Hct and Plt showed no significant change.The blood routine returned to the level before G-CSF mobilization 1-2 days after blood donation.No physical discomfort occurred during the one week after blood donation.Four patients with granulocyte deficiency complicated with multidrug-resistant bacterial infection, who failed to respond to antibiotic treatment, were transfused with 29 U AG, with no adverse reactions and no obvious change in blood routine, but the infection symptoms were improved significantly judged from clinical manifestation, bacterial culture results, temperature monitoring and CT examination, suggesting that the AG infusion was effective.Among the 4 patients, 1 was cured and discharged, 1 gave up treatment, 1 died of sepsis, and 1 died of multiple organ failure. 【Conclusion】 It is safe to collect AG from blood donors mobilized by G-CSF through blood cell separator, and the AG products basically meet the national quality requirements and the treatment needs.Sustained high-dose AG transfusion has a significant effect on infection control in patients with agranulocytosis combined with refractory multidrug-resistant bacterial or fungal infection.

Analysis of Agranulocytosis Time and Its Influencing Factors in Patients with Hematological Malignancies Treated with rhIL-11 combined rhG-CSF / 中国实验血液学杂志

OBJECTIVE@#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.@*METHODS@#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.@*RESULTS@#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).@*CONCLUSION@#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.

Methimazole induced agranulocytosis and hemophagocytic syndrome: One case report / 中华内分泌代谢杂志

In order to improve the level of diagnosis and treatment, we report a rare case of hyperthyroidism patient occurred agranulocytosis and hemophagocytic syndrome after taking methimazole. After methimazole treatment, agranulocytosis and infection was developed, but was improved temporarily after treatment. However because of infection, the condition was rapidly developed into hemophagocytic syndrome. Finally, the patient improved rapidly with the treatment of dexamethasone.

Agranulocitosis febril y artropatía reactiva asociada a consumo de cocaína en un paciente HLA B27 positivo / Febrile agranulocytosis and reactive arthropathy associated with cocaine consumption in an HLA B27 positive patient

Resumen La agranulocitosis asociada al consumo de cocaína es un fenómeno vinculado a la presencia de levamisol, un agente antihelmíntico e inmunomodulador, usado como adulterante de la cocaína. Esta reacción puede presentarse con mayor frecuencia en personas con HLA B27. Además de la agranulocitosis, las personas que consumen cocaína adulterada con levamisol pueden desarrollar fiebre, lesiones en piel, artralgias y, menos frecuentemente, artritis y entesitis inflamatoria. Presentamos el caso de un paciente consumidor de cocaína, con genotipo HLA B27, que desarrolló agranulocitosis febril y artropatía reactiva. En sangre se detectó la presencia de ANCA p, ANCA atípico y MPO, y fueron excluidas otras causas de agranulocitosis. Fue tratado con corticoides y posteriormente metotrexato, terapia de deshabituación, con buena evolución.

Abstract Agranulocytosis associated with cocaine use is a phenomenon linked to the presence of levamisole, an anthelminthic and immunomodulating agent, used as an adulterant to cocaine. This reaction has been associated with the presence of HLA B27. In addition to agranulocytosis, people who use levamisole-adulterated cocaine may develop fever, skin lesions, arthralgias, and less frequently, inflammatory enthesitis and arthritis. We present the case of a cocaine-consuming patient with HLA B27 genotype, who developed febrile agranulocytosis and inflammatory arthropathy. The presence of p ANCA, atypical ANCA and MPO was detected in blood, and other causes of agranulocytosis were excluded. He was treated with corticosteroids and later methotrexate, therapy for addiction, with good evolution.

Utilidad del carbonato de litio, yoduro inorgánico y plasmaféresis en una paciente con hipertiroidismo severo y agranulocitosis por tiamazol en tiempos de COVID-19 / Usefulness of lithium carbonate, inorganic iodide and plasmapheresis in a patient with severe hyperthyroidism and agranulocytosis due to thiamazole in times of COVID-19

RESUMEN Mujer de 43 años con diagnóstico reciente de enfermedad de Graves-Basedow ingresa a urgencias por infección de tejidos blandos, agranulocitosis por tiamazol e hipertiroidismo descompensado. La paciente requería tratamiento definitivo para hipertiroidismo, pero dado el contexto de la pandemia por SARS-CoV-2 no se contaba con yodo radioactivo (131I) por lo que se planteó la tiroidectomía total. Se necesitaba una preparación preoperatoria rápida y eficaz por lo que se decidió compensar su hipertiroidismo con lugol, carbonato de litio, dexametasona y finalmente plasmaféresis antes de cirugía. Con ello se logró disminuir los niveles de hormonas tiroideas en el tiempo deseado y se procedió al tratamiento quirúrgico definitivo. Se presenta el caso por lo anecdótico y por ser necesario el conocimiento del manejo en escenarios, como esta pandemia, donde no haya acceso a 131I.

ABSTRACT A 43-year-old woman with a recent diagnosis of Graves-Basedow disease was admitted to the emergency room due to soft tissue infection, thiamazole agranulocytosis, and severe hyperthyroidism. The patient required definitive treatment for hyperthyroidism, but given the context of the SARS-COV-2 pandemic, radioactive iodine was not available, so she prepared for total thyroidectomy. A rapid and effective preoperative preparation was required, so it was decided to compensate her hyperthyroidism with lugol, lithium carbonate, dexamethasone and finally plasmapheresis before surgery. Thyroid hormone levels normalized in a short time, and the thyroidectomy was performed. The case is presented because of the anecdotal and because knowledge of management in scenarios, such as this pandemic, where there is no access to 131I.

Presentación de un caso de agranulocitosis por propiltiouracilo / Presentation of a case of agranulocytosis caused by propylthiouracil

Se estudió una paciente de 33 años de edad con antecedentes patológicos de Bocio tiroideo difuso desde hace 8 años, que acude al cuerpo de guardia por presentar falta de aire, fiebre de 39-40 °C, dolor de garganta y palpitaciones hace alrededor de tres días. Al examen físico se le constató exoftalmos, mucosas hipocoloreadas y faringe purulenta y punteada de color blanquecina, artralgia y taquicardia. Referente a los exámenes complementarios presentó anemia, leucopenia y pancitopenia luego de haber consumido propiltiouracilo (50mg) por un período prolongado; por lo que se concluye como agranulocitosis como consecuencia de una reacción adversa al propiltiouracilo. Luego de ser tratada la paciente se recupera de su gravedad con el uso de factores estimulantes de colonias de granulocitos(AU)

A female 33-year-old patient with an 8-year history of diffuse thyroid goiter presents at the emergency service with shortness of breath, a 39-40ºC fever, a sore throat and palpitation of 3 days' evolution. Physical examination revealed exophthalmos, hypopigmented mucosas, a purulent pharynx dotted with whitish spots, arthralgia and tachycardia. Complementary tests found anemia, leukopenia and pancytopenia upon consumption of propylthiouracil (50 mg) for a long period. The diagnosis is agranulocytosis resulting from an adverse reaction to propylthiouracil. After being treated the patient recovered from her severe status with the use of granulocyte colony stimulating factors(AU)

Agranulocitosis inducida por clozapina / Clozapine-induced agranulocytosis

RESUMEN Clozapina, actualmente, sigue siendo el gold standard para la esquizofrenia resistente al tratamiento, pero solo bajo un adecuado monitoreo hematológico, porque está asociada a agranulocitosis. Clozapina se metaboliza produciendo N-desmetilclozapina (farmacológicamente activa), el N-óxido de clozapina (inactivo) y especies reactivas de oxígeno (ion nitrenio). El recuento de neutrófilos <1000 células/mm3 corresponde a un estado de neutropenia. La agranulocitosis es un estado grave de neutropenia con un recuento absoluto de neutrófilos <500 células/mm3. Clozapina se asocia con la agranulocitosis en aproximadamente el 0,8 % de los pacientes, y el riesgo aumenta con la edad y en mujeres. Existen dos mecanismos que explican la agranulocitosis inducida por clozapina: inmunológico (respuesta mediada por el sistema inmunitario contra neutrófilos haptenizados) y tóxico (por acción de los metabolitos N-desmetilclozapina y ion nitrenio). La farmacogenética es una herramienta valiosa para conseguir la referida medicina personalizada, al adaptar e individualizar el tratamiento basado en los marcadores genéticos de cada paciente. Numerosos estudios han demostrado una asociación potencial de la agranulocitosis inducida por clozapina con ciertos haplotipos HLA (HLA-B38, DR4, DQw3, DQB1). Luego que un paciente ha presentado agranulocitosis, se conocen tres mecanismos de reexposición a clozapina: simple, con litio y con factores estimuladores de colonias de granulocitos. Debido al riesgo de agranulocitosis, las formulaciones de clozapina están disponibles solo a través de una distribución controlada, con un registro detallado de los pacientes y con una farmacovigilancia sistematizada y obligatoria.

ABSTRACT Clozapine currently remains the gold standard for treatment-resistant schizophrenia, but only under an adequate hematological monitoring, because it is associated with agranulocytosis. Clozapine is metabolized to produce pharmacologically active N-desmethylclozapine, inactive clozapine N-oxide and reactive oxygen species (nitrenium ion). A neutrophil count < 1000 cells/mm3 corresponds to a state of neutropenia. Agranulocytosis is a severe state of neutropenia with an absolute neutrophil count < 500 cells/mm3. Clozapine is associated with agranulocytosis in approximately 0.8 % of the patients, with an increased risk in older people and women. There are two mechanisms that explain the clozapine- induced agranulocytosis: immunological (response mediated by the immune system against haptenized neutrophils) and toxic (by the action of the metabolites N-desmethylclozapine and nitrenium ion). Pharmacogenetics represents a valuable tool to achieve the so-called personalized medicine by adapting and individualizing the treatment based on the genetic markers of each patient. Several studies have shown a potential association of clozapine-induced agranulocytosis with certain HLA haplotypes (HLA-B38, DR4, DQw3 and DQB1). After a patient has presented agranulocytosis, three mechanisms of clozapine rechallenge are known: simple, with lithium and with factors that stimulate granulocyte colonies. Due to the risk of agranulocytosis, clozapine formulations are available only through a controlled distribution, with a detailed record of the patients, and with a mandatory and systematized pharmacovigilance.

Case analysis of antithyroid drug-induced agranulocytosis combined with fatal complications / 西安交通大学学报(医学版)

Objective: To investigate the clinical characteristics of patients with antithyroid drug (ATD)-induced agranulocytosis in the treatment of hyperthyroidism and analyze factors associated with the death rate of patients with fatal outcomes. Methods:Patients diagnosed with ATD-induced agranulocytosis in Department of Endocrinology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2018, were included in this study and their medical records were reviewed retrospectively. We compared the clinical characteristics of patients in death group and survival group. Results: We recruited 70 patients with ATD-induced agranulocytosis in the study. Five of them died. All fatal cases were females, aged between 33 to 54 years. Three patients also had hyperthyroidism crisis, and two had hyperthyroid heart disease. Compared with the survival cases of ATD-induced agranulocytosis, patients with fatal agranulocytosis were elderly [47.00±8.12)years vs. (35.58±11.10) years, P=0.028] and had a longer duration of hyperthyroidism [1 800 (315-2 880)d vs. 60(40-120)d, P=0.002]. The interval days between symptoms and the diagnosis of agranulocytosis were significantly longer in patients with fatal cases than the survival ones[5.0(3.5-11.0)d vs. 0(0-2.5) d, P=0.002]. In addition, the proportion of patients with hyperthyroid crisis was greater in the death group (60% vs. 0%, P<0.001). Conclusion: Age, duration of hyperthyroidism, and timely diagnosis of agranulocytosis could affect the mortality of agranulocytosis. Mortality in patients with hyperthyroidism was significantly increased. It is recommended that patients with hyperthyroidism should be reminded to monitor routine blood cells immediately. In the event of agranulocytosis, other methods should be chosen as soon as possible to treat hyperthyroidism and avoid serious outcomes.

Propylthiouracil-induced agranulocytosis as a rare complication of antithyroid drugs in a patient with Graves' disease

SUMMARY INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management. CASE: RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression. DISCUSSION: We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications. CONCLUSION: Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

RESUMO INTRODUÇÃO: A doença de Graves (DG) é uma doença autoimune caracterizada por hipertireoidismo. As drogas antitireoidianas (DAT) são opções terapêuticas disponíveis. A agranulocitose é uma complicação rara, potencialmente fatal desta terapia. Neste estudo, relatamos um caso de agranulocitose induzida por propiltiouracil (PTU) em paciente com DG e as dificuldades do manejo clínico. RELATO DE CASO: RNBA, sexo masculino, 30 anos, com DG, tratado com PTU. Evoluiu com faringoamigdalite, sendo o PTU suspenso e antibióticos, filgrastim, propranolol e prednisona, iniciados. Devido à descompensação do hipertireoidismo, iniciou carbonato de lítio (CL), dexametasona e a solução de Lugol. A tireoidectomia total (TT) foi realizada com boa evolução pós-operatória. DISCUSSÃO: Descrevemos caso de paciente jovem, sexo masculino, com DG. Para o tratamento do hipertireoidismo, as tionamidas são opções efetivas. A agranulocitose induzida por DATs é uma complicação rara, definida como a ocorrência de contagem de granulócitos <500/mm3 após uso de dats. PTU foi suspenso e foram prescritos filgrastim e antibiótico. O radioiodo (RAI) ou a cirurgia são alternativas terapêuticas. Devido a problemas com o uso de DAT, a TT foi proposta. A preparação pré-operatória foi realizada com betabloqueador, glicocorticoide, CL e solução de Lugol. A colestiramina também é uma opção para controlar o hipertireoidismo. A TT foi realizada sem complicações pós-operatórias. CONCLUSÃO: A agranulocitose induzida por drogas antitireoidianas é uma complicação rara. Com a contraindicação às DATs, RAI e cirurgia são opções terapêuticas definitivas para DG. Os betabloqueadores, glicocorticoides, CL, iodo e a colestiramina podem ser uma terapia adjuvante para o hipertireoidismo.

Clinical characteristics and related factors of pneumonia in patients with aplastic anemia / 中国感染与化疗杂志

objective To analyze the clinical characteristics of pneumonia in patients with aplastic anemia for improving early prevention and clinical diagnosis. Methods A retrospective analysis was conducted for patients with aplastic anemia treated in our hosipital from June 2013 to April 2018. The clinical data of pneumonia were reviewed and analyzed in terms of radiological findings, pathogen distribution, and related risk factors. Results The clinical manifestations are atypical in patients with aplastic anemia. The imaging findings suggested that the infection was mainly bilateral pulmonary infection. The common pathogens were gram-negative bacteria such as Klebsiella pneumoniae. Disease type, agranulocytosis and low serum albumin level were independent risk factors for pneumonia in patients with aplastic anemia. Regular immunosuppressive therapy is a protective factor for pneumonia in patients with aplastic anemia. Conclusions The clinical manifestations of pneumonia are diverse in patients with aplastic anemia. The pathogens are mainly gram-negative bacteria. Empirical use of β-lactam-β-lactamase inhibitor combinations or quinolones is beneficial for controlling infection. Regular immunosuppressive therapy, recovery of hematopoietic function, nutritional support are effective measures to reduce the incidence of pneumonia in patients with aplastic anemia.

Análisis de la incidencia de eventos adversos relacionados a aplicación de dipirona / Analysis of the incidence of adverse events related to the administration of dipyrone

Abstract Introduction: Notwithstanding the widespread use of dipyrone, its association with adverse events has reduced its clinical use, with Agranulocytosis being the most studied adverse event, and apparently of primary clinical impact. Studies in Latin America have disputed these claims. Objective: To analyze the incidence and reports of adverse events associated with the use of dipyrone in a high complexity hospital. Materials and methods: Descriptive observational study of an incident cohort. Population: Patients receiving dipyrone during their hospital stay. Quantitative analysis of incidents and description of dipyrone-associated adverse events. Results: Incidence of global adverse events=0.3% (in 48,946 doses of dipyrone prescribed to 2747 patients). No cases of Agranulocytosis. A total 100% non-severe adverse events. (All were associated with toxidermia). Conclusion: A low incidence of dipyrone-associated adverse events is reported. Optimal reporting of institutional adverse events is controversial, and the recommendation is to measure any adverse events with a more rigorous follow-up of patients using dipyrone, and a clear and specific standardization of the guidelines for improved prescription and medical control.

Resumen Introducción: A pesar del amplio espectro de uso de la dipirona, su asociación a eventos adversos ha reducido su empleo clínico, siendo la agranulocitosis el evento adverso más estudiado, y al parecer de mayor impacto clínico. Estudios en América Latina han controvertido dichas afirmaciones. Objetivo: Analizar la incidencia y reporte de eventos adversos asociados al uso de dipirona en un hospital de alta complejidad. Materiales y métodos: Estudio observacional descriptivo de una cohorte Incidente. Población: Pacientes usuarios de dipirona durante su estancia hospitalaria. Análisis cuantitativo de Incidencias, y descriptivo de los casos incidentes de adversos relacionados al uso de dipirona. Resultados: Incidencia de Eventos Adversos Globales=0,3% (En 48.496 dosis de dipirona formuladas en 2.747 pacientes). Ningún caso de Agranulocytosis. 100% de eventos adversos no severos (Todos asociados a reacción toxidérmica). Conclusiones: Se reporta una baja incidencia de eventos adversos relacionados al uso de dipirona. Se controvierte la óptima ejecución de los reportes de eventos adversos institucionales. Se sugiere la realización de la medición de eventos adversos posterior a un más riguroso seguimiento de los pacientes usuarios de este medicamento, y a una estandarización clara y puntual de pautas para una mejor prescripción y control médico luego de su formulación.

Neutropenia severa inducida por propiltiuracilo / (Severe neutropenia induced by propylthiuracil)

Resumen Los pacientes con hipertiroidismo tienen varias opciones de tratamiento. El tratamiento de la enfermedad de Graves consiste en bloquear el exceso de hormonas tiroideas empleando tionamidas, tiroidectomía o terapia con I131. Los agentes antitiroideos como el metimazol, carbimazole, propiltiuracilo, son efectivos para controlar el hipertirodismo en pacientes con enfermedad de Graves, pero tienen efectos adversos incluyendo, alergias, gastritis, hepatitis y agranulocitosis. Se presenta un paciente hipertiroideo con neutropenia severa durante tratamiento con propiltiuracilo.

Abstract Patients with hyperthyroidism have several treatment options. The treatment of Graves' disease consists of blocking the excess of thyroid hormones using thionamides, thyroidectomy or I131 therapy. Antithyroid agents such as methimazole, carbimazole, propylthiuracil are effective in controlling hyperthyroidism in patients with Graves' disease, but they have adverse effects including, allergies, gastritis, hepatitis and agranulocytosis. We present a hyperthyroid patient with severe neutropenia during treatment with propylthiuracil.

Clostridium perfringens bacteremia with malignant hematopathy:a case report and review of literatures / 中国感染控制杂志

Infection is an important cause of higher mortality in patients with hematological diseases than healthy people, and fever is often the only indication of the disease.Clostridium perfringens(C.perfringens)is a grampositive anaerobic bacillus of the Clostridiumgenus, it belongs to the normal flora of the intestinal tract and is not pathogenic in normal condition.However, when intestinal flora is imbalanced due to low hypoimmunity of human body or influenced by such factors as diet, medicine, environment and other factors, it can enter the blood and cause bacteremia.At present, it has never been reported that bacteremia was caused by C.perfringens in patients with malignant hematological diseases accompanied by neutropenia, this article reported the diagnosis and treatment of C. perfringens bloodstream in one patient with malignant hematopathy, so as to provide basis for diagnosis and treatment of the disease.

Ecthyma gangrenosum and agranulocytosis in a previously healthy 12-month-old girl: Report of 1 case with a literature review

Ecthyma gangrenosum (EG) is a rare skin manifestation which starts with a maculopapular eruption and followed by a necrotic ulcer covered with black eschar. EG usually occurs in immunosuppressed patients with Pseudomonas aeruginosa sepsis. We present a previously healthy 12-month-old girl with EG by P. aeruginosa and agranulocytosis due to influenza A and then rhinovirus infection, without bacteremia. It is important for allergists to culture wound and differentiate EG from other skin disorders including Tsutsugamushi disease and initiate appropriate empiric antipseudomonal antibiotic treatment, and to evaluate for possible immunodeficiency, even in a healthy child.