Agranulocitosis secundaria a uso de vancomicina en pediatría. reporte de caso

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.

Autoimmune Neutropenia Associated With HHV-6 Virus Infection: A Case Report.

Background: Autoimmune neutropenia (AIN) is divided into primary and secondary forms. The former is more prevalent in children and is usually a self-limiting disease. Secondary AIN is more common in adults and often occurs in the setting of another autoimmune disorder or secondary to infections, malignancies or medications. Several viral and bacterial pathogens were described to trigger AIN. Here we report a case of AIN in an adult woman associated with human herpesvirus-6 (HHV-6) infection. Case Presentation: We report a case of AIN in an adult woman associated with HHV-6 infection. The patient presented to the emergency department with fever and painful genital ulcers. Upon arrival, her laboratory workup demonstrated severe neutropenia and elevated inflammatory markers. She was hospitalized and underwent a thorough infectious, hematological, autoimmune and inflammatory workup. Malignancy was also excluded using an advanced whole body radiological scan. Serological tests confirmed the presence of both acute and chronic types of HHV-6 antibodies, at very high titers. Polymerase chain reaction demonstrated a numerous copies of the virus in the patient's blood. Specific immunofluorescence test confirmed the diagnosis of autoimmune neutropenia. Conclusion: Secondary AIN is a rare disease that may affect all range of ages. The adult type is a challenging disorder that has different etiologies and may be triggered by a variable infectious pathogen. The finding of HHV-6 as a possible culprit pathogen may warrant physicians into widening the evaluation and include HHV-6 in the analysis.

Discrasias sanguíneas por medicamentos con inicio de síntomas respiratorios / Drug-induced blood dyscrasias with onset of respiratory symptoms

Paciente diagnosticada de colitis ulcerosa y artritis reumatoide que está siendo tratada con mesalazina e hidroxicloroquina y que presenta síntomas catarrales similares a los de la COVID-19. El seguimiento farmacoterapéutico (SFT) realizado a la paciente permite asociar estos síntomas con un efecto secundario debido a los medicamentos que toma, consistente en discrasias sanguíneas. La intervención, realizada con el propio estado de situación, para informar al médico, consigue que éste realice modificaciones del tratamiento hasta conseguir el control de la enfermedad mediante disminución de las dosis de los medicamentos utilizados. (AU)

Adecuación de la seguridad del metamizol y agranulocitosis / Adequacy of the safety of metamizole and agranulocytosis

Objetivo: Analizar si la nota informativa de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), de 30 de octubre del 2018, sobre agranulocitosis y metamizol contiene la información precisa y necesaria para proteger a los pacientes de la aparición de esta reacción adversa (RA) y si la documentación oficial de los medicamentos con metamizol para médicos, farmacéuticos y población general está adaptada a las directrices de la AEMPS para disminuir el riesgo. Emplazamiento y participantes: Nota informativa, búsqueda bibliográfica, información sobre los medicamentos con metamizol comercializados en España en la Agencia Europea del Medicamento, fichas técnicas, prospectos, base de datos de información sanitaria Bot PLUS y Catálogo de Especialidades Farmacéuticas. Notificación de 4casos de agranulocitosis por metamizol posteriores a la fecha de la nota informativa. Intervenciones y mediciones principales: Comparación de los puntos clave de la nota informativa y de los documentos oficiales sobre metamizol con la bibliografía. Descripción de 4casos de agranulocitosis por metamizol y aplicación del algoritmo de causalidad y gravedad. Resultados: La nota informativa presenta ausencias y dudas respecto a la bibliografía y al uso de metamizol en la práctica asistencial. Los documentos oficiales presentan faltas de actualización, indicaciones no aprobadas y dosis superiores a las recomendadas. La nota informativa no ha frenado la presentación de casos de agranulocitosis por metamizol. Conclusiones: La nota informativa de la AEMPS es mejorable y es necesario actualizar los documentos oficiales de información sobre el metamizol para profesionales sanitarios y pacientes para disminuir el riesgo de agranulocitosis.(AU)

Objective: To analyze whether the drug safety update issued by the Spanish Agency of Medicines and Healthcare Products (AEMPS), dated October 30, 2018, on agranulocytosis and metamizole contains accurate and necessary information to protect patients from the presentation of this adverse reaction (AR) and if the official documentation of medicines containing metamizole for doctors, pharmacists and the general population conforms to the guidelines of the AEMPS to reduce this risk. Setting and participants: Drug safety update, bibliographic search, information at the European Medicines Agency on metamizole drugs marketed in Spain, technical datasheets, leaflets, Bot PLUS Health Information Database and Catalog of Pharmaceutical Specialties. Notification of 4cases of agranulocytosis due to metamizole after the drug safety update was issued. Main interventions and measurements: Comparison of the key points of the drug safety update and official documents on metamizole with the bibliography. Description of the 4cases of agranulocytosis due to metamizole and application of the causality and severity algorithm. Results: The drug safety update contains omissions and contradiction in respect to the bibliography and the actual use of metamizole in healthcare practice. The official documents show a lack of updating, unapproved indications and doses higher than those recommended. The drug safety update has not stopped the presentation of cases of agranulocytosis due to metamizole. Conclusions: The AEMPS drug safety update can be improved and it is necessary to update the official information documents on metamizole for health professionals and patients in order to decrease the risk of agranulocytosis.(AU)

[Adequacy of the safety of metamizole and agranulocytosis]. / Adecuación de la seguridad del metamizol y agranulocitosis.

OBJECTIVE: To analyze whether the drug safety update issued by the Spanish Agency of Medicines and Healthcare Products (AEMPS), dated October 30, 2018, on agranulocytosis and metamizole contains accurate and necessary information to protect patients from the presentation of this adverse reaction (AR) and if the official documentation of medicines containing metamizole for doctors, pharmacists and the general population conforms to the guidelines of the AEMPS to reduce this risk. SETTING AND PARTICIPANTS: Drug safety update, bibliographic search, information at the European Medicines Agency on metamizole drugs marketed in Spain, technical datasheets, leaflets, Bot PLUS Health Information Database and Catalog of Pharmaceutical Specialties. Notification of 4cases of agranulocytosis due to metamizole after the drug safety update was issued. MAIN INTERVENTIONS AND MEASUREMENTS: Comparison of the key points of the drug safety update and official documents on metamizole with the bibliography. Description of the 4cases of agranulocytosis due to metamizole and application of the causality and severity algorithm. RESULTS: The drug safety update contains omissions and contradiction in respect to the bibliography and the actual use of metamizole in healthcare practice. The official documents show a lack of updating, unapproved indications and doses higher than those recommended. The drug safety update has not stopped the presentation of cases of agranulocytosis due to metamizole. CONCLUSIONS: The AEMPS drug safety update can be improved and it is necessary to update the official information documents on metamizole for health professionals and patients in order to decrease the risk of agranulocytosis.

Agranulocitosis secundaria a clozapina: a propósito de 2 casos / Agranulocytosis secondary to clozapine: Report of 2 cases

La clozapina es un fármaco de referencia en el tratamiento de la esquizofrenia refractaria. El temor a la aparición y el manejo de efectos secundarios graves, especialmente agranulocitosis, hace que los profesionales se retraigan a la hora de usarlo.En este artículo se describe un caso de inicio de tratamiento con múltiples complicaciones médicas tras la aparición de neutropenia y un caso de reexposición al fármaco tras un primer intento frustrado por agranulocitosis. En ambos hubo que retirar definitivamente el tratamiento con clozapina, pero los pacientes se recuperaron sin secuelas.Consideramos que la aportación de casos en los que se apreciaron problemas puede enriquecer la formación e inspirar más confianza entre los psiquiatras y residentes en el manejo de casos similares. (AU)

Clozapine is a gold standard in the treatment of refractory schizophrenia. The fear of the appearance and management of serious side effects, especially agranulocytosis, causes professionals not to use it frequently.This article describes a case of initiation of treatment with multiple clinical complications after the onset of neutropenia and a case of drug reexposure after a first attempt frustrated by agranulocytosis. In both cases, clozapine treatment had to be definitively withdrawn, but the patients full recovered.We believe that the presentation of cases in which relevant problems appeared c ould enrich the formation and inspire confidence among psychiatrist and residents in the management of similar cases. (AU)

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.

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.

Acute agranulocytosis after oral administration of dabigatran: a rare case report and a short review of literature.

This case report describes agranulocytosis immediately after oral administration of dabigatran in a 68 years old man with atrial fibrillation (AF). Dabigatran is an oral, reversible and competitive thrombin inhibitor that has shown promising results. In patients with atrial fibrillation of RE-LY study (Randomized Evaluation of Long-Term Anticoagulant Therapy), dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. Dabigatran is administered as a prodrug and the peak of the plasma concentrations occurs within 2 h of ingestion. Agranulocytosis is characterized by a severe decrease or lack of circulating granulocytes. This rare event can be found among people taking dabigratan, especially for people who are female, over the age of 60, who took the drug for < 1 month. Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. The patient's white blood cell count increased abruptly after discontinuation of the drug, suggesting an immune response caused by dabigatran. Although anticoagulant drugs are commonly used to treat atrial fibrillation, attention should be paid to this aspect and possible drug interactions.

Increase in white cell and neutrophil counts during the first eighteen weeks of treatment with clozapine in patients admitted to a long-term psychiatric care inpatient unit. / Aumento en los recuentos de leucocitos y neutrófilos durante las primeras 18semanas de tratamiento con clozapina en pacientes ingresadas en una unidad de cuidados psiquiátricos prolongados.

INTRODUCTION: Clozapine is an antipsychotic drug that has shown to be more effective than other antipsychotics in the treatment of schizophrenia, but its use is limited due to its side effects, particularly by the risk of causing agranulocytosis. A study was made on the variations in white cell and neutrophil counts in patients treated with clozapine in a Long-term Psychiatric Unit. METHODS: A retrospective observational study was conducted with a sample of women of our long-term psychiatric care unit who had been treated with clozapine. A study was made on the variations in white cell and neutrophil counts during the first 18 weeks of treatment, as well as the onset of leukopenia, neutropenia, agranulocytosis, and the influence of concomitant drugs. RESULTS AND CONCLUSIONS: The study included 55 patients on treatment with clozapine. The incidence rate of neutropenia was 1.82% (95% CI; 0.05-10.13). The incidence rate of leukopenia and agranulocytosis was 0%. An increase in white cell and neutrophil counts from baseline to week 3-4 was observed. Only small variations were observed after this time, but the counts remained higher than the initial values. These changes were statistically significant in the white cell count: One-way repeated ANOVA with Greenhouse-Geisser correction F (11.47, 37) = 2.114 (P= .011); and in neutrophils: One-way repeated ANOVA with Greenhouse-Geisser correction F (10.3, 37)=3.312 (P=.0002), and MANOVA F (18, 37)=2.693 (P=.005), ŋ2P=0.567. The influence of concomitant drugs (lithium, valproic and biperiden) was not significant on the overall increase found in white cells or neutrophils (MANOVA).

Dipyrone-related granulocytopenia. Case report / Granulocitopenia por dipirona: reporte de caso

Abstract Introduction: Dipyrone has been positioned in several countries as one of the first over-the-counter options for pain management. Its possible adverse effects are known worldwide; among them, agranulocytosis is the most lethal, with a mortality of approximately 10% and an associated risk of 1 per 1,000,000 patients. Clinical findings, interventions, and outcomes: A case of a patient who, after 23 days of using dipyrone for pain management, developed a progressive drop in leukocyte count. Other potential causes of the event were ruled out. After dipyrone discontinuation, leukocyte counts returned to their normal values. Conclusion: The probable diagnosis of granulocytopenia as a dipyrone-related adverse drug reaction was established. Although rare, dipyrone-related granulocytopenia, may occur in patients who use this medication for long periods.

Resumen Introducción: La dipirona se ha posicionado en varios países como una de las primeras opciones de venta libre al público para el manejo del dolor. Sus posibles efectos adversos son conocidos a nivel mundial; entre ellos, la agranulocitosis es la más letal con una mortalidad aproximada del 10% y un riesgo asociado de 1 por cada 1.000.000 pacientes. Hallazgos clínicos, intervención y resultados: Se presenta un caso de una paciente que luego de recibir 23 días seguidos dipirona para el manejo del dolor presentó disminución progresiva de los leucocitos documentados en el hemograma. Se descartaron otras posibles causas de dicho evento. Luego de suspender la administración de la dipirona los leucocitos volvieron a sus valores normales. Conclusión: Se estableció la sospecha de diagnóstico probable de granulocitopenia como reacción adversa medicamentosa por dipirona. La granulocitopenia por dipirona aunque poco frecuente, se puede presentar en pacientes que la reciben por largos periodos de tiempo.

Graves' disease in a 3 year-old patient with agranulocytosis due to anti-thyroid drugs: Radioiodine ablation therapy as an effective alternative. / Enfermedad de Graves en un paciente de 3 años con agranulocitosis asociada a fármacos antitiroideos: terapia ablativa con radioyodo como una alternativa eficaz.

The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with 131I ablation therapy. The relevance of the article is that Graves' disease is uncommon in the paediatric age range (especially in children younger than 6 years old), and developing complications due to a possible late diagnosis. Agranulocytosis as a potentially serious adverse effect following the use of anti-thyroid drugs, and the few reported cases of ablation therapy with 131I at this age, makes this case unique.

Agranulocitosis secundaria a clozapina: un estudio descriptivo en pacientes chilenos / Agranulocytosis secondary to clozapine: a descriptive study in Chilean patients

Introduction: Agranulocytosis is one of the most serious adverse effects of clozapine. The Latin American literature is currently scarce on the subject. Objective: To describe the occurrence of agranulocytosis or leukopenia secondary to clozapine and its associated factors in a sample of Chilean patients between the years 2011-2016. Materials and Methods: An observational, retrospective type of study was designed base on virtual information from the National Pharmacovigilance Registry and definition of alarm levels according to the Technical Standard of clozapine, later performing statistical analysis. Results: total n 60 patients, 8 patients with some alarm event; Alarm 1:5; Alarm II: 1; Alarm III: 2. Alarms were distributed between week 1 and week 242. The incidence was higher between weeks 0 and 12 (1.26%). Until week 18,53% of alarms I and 100% of alarms III occurred, alarm II occurred in month 10. Discussion: When comparing patients with and without alarm, significant differences were found in the basal count of leukocytes and neutrophils, with no differences in age and sex. Patients who presented alarms and/or lower baseline leukocyte or neutrophil counts could eventually benefit from a longer weekly follow-up. Conclusion: This study constitutes the first step towards exploring the adverse effects profile of clozapine in Chilean patients.

Introducción: La agranulocitosis es uno de los efectos adversos más graves de la clozapina. Existe escasa literatura latinoamericana al respecto. Objetivo: Describir la ocurrencia de agranulocitosis o leucopenia secundaria a clozapina y sus factores asociados en una muestra de pacientes chilenos entre los años 2011-2016. Materiales y Métodos: Se diseñó un estudio de tipo observacional, retrospectivo con información virtual del Registro Nacional de Farmacovigilancia y definición de niveles de alarma según Norma Técnica de clozapina, realizando posteriormente análisis estadístico. Resultados: En total 60 pacientes, 8 pacientes con algún evento de alarma; Alarma 1:5; Alarma II: 1; Alarma III: 2. Las alarmas se distribuyeron entre la semana 1 y la 242. La incidencia fue mayor entre las semanas 0 y 12 (1,26%). Hasta la semana 18 habían ocurrido el 53% de alarmas I y 100% de alarmas III, la alarma II ocurrió en el mes 10. Discusión: Al comparar a los pacientes con y sin alarma, se encontraron diferencias significativas en el conteo basal de leucocitos y neutrófilos, sin diferencias en edad y sexo. Aquellos pacientes que han presentado alarmas y/o menores conteos basales de leucocitos o neutrófilos, eventualmente, podrían beneficiarse de un seguimiento semanal más prolongado. Conclusión: Este estudio corresponde a un primer paso hacia explorar el perfil de efectos adversos de clozapina en pacientes chilenos.

3 cases of cocaine - levamisole syndrome in Medellín / Presentación de tres casos de síndrome cocaína - levamisol en Medellín

El levamisol es un antihelmíntico de uso veterinario que ha sido utilizado como aditivo a la cocaína con el objetivo de aumentar los efectos psicotrópicos de dicha sustancia. Esta mezcla produce reacciones como agranulocitosis, vasculitis cutánea y modulación del sistema inmune. Solamente el reconocimiento, tratamiento adecuado y la suspensión del consumo de esta sustancia lleva a la desaparición de las lesiones y sugiere fuertemente el diagnóstico. Presentamos tres casos de síndrome cocaína/levamisol en Medellín y una revisión de la literatura con algunos conceptos de esta enfermedad.

Levamisole, an anthelmintic veterinary product is known to be used as an additive to cocaine that enhances the psychotropic effects of this substance. This mixture leads to reactions such as agranulocytosis, skin vasculitis and modulation of the immune system. Only the proper recognition, treatment of this entity and discontinuation of this substance consumption, leads to the disappearance of lesions; strongly suggesting the diagnosis. We present three cases of cocaine/levamisole syndrome in the city of Medellin and a review of the literature with some concepts related to this pathology.

[Hematological Evaluation and Monitoring in Adult Patients Diagnosed With Schizophrenia]. / Evaluación y seguimiento hematológico del paciente con diagnóstico de esquizofrenia.

OBJECTIVES: To guide the clinician in taking decisions on the best strategies for assessing and monitoring the risk of blood disorders in adults diagnosed with schizophrenia in pharmacological treatment. METHOD: A clinical practice guideline was developed following the guidelines of the Methodological Guide of the Ministry of Social Protection to collect evidence and grade recommendations. De novoliterature researchwas performed. RESULTS: With the use of antipsychotics there isriskofreducción in the leukocyte count and the risk of agranulocytosis,the later associated with the use of clozapine, although it is a rare event(0.8%) can be fatal; this effect occurs most frequently in the first twelve weeks of treatment and the risk is maintained aroundthe first year of it. CONCLUSION: The recommendations were considered strongin all hematologic related monitoring.A blood count should be taken at the start of pharmacological treatment. If the patient is started on clozapine one shouldbe taken weekly during the first three months, monthly until completing one year and every six months thereafter. If there is a decrease in white blood cell count the patient should be monitored regularly, stopping if is a less than 3,500 cells/mm(3) and consider referral if is less than 2,000 cells/mm(3).