Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia

ABSTRACT Introduction: We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods: Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results: In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9-34.2, p = 0.004). Conclusions: Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

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.

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.

Nelore females along a new Brazilian agricultural frontier: hematological and clinical-biochemical approaches / [Abordagens hematológicas e bioquímicas clínicas de fêmeas Nelore na nova fronteira agrícola brasileira]

The Nelore breed is the second largest bovine breed in the world and has actively participated in the expansion of new Brazilian agricultural frontiers. In this context, the purpose of this study was to determine the hematological and biochemical reference intervals of healthy Nelore matrices raised under an extensive regime without supplementation along southwest of Piauí state. Blood samples were collected from fifty-five multiparous female of the Nelore breed. Biochemical and hematological parameters were analyzed using a parametric statistical method with 95% CI of reference limits. The average values of red blood cells, hemoglobin as well as hematimetric indices showed reference ranges similar to reference standards. The hematocrit as well as granulocytes and agranulocytes presented alterations typical of animals raised in environments with higher temperatures. Mineral, enzymatic, protein and metabolic profiles were similar to other bovine breeds but with a narrower range of values. However, lower mean values were observed for levels of ionized calcium, total protein and urea. Nelore females present slightly different biochemical and hematological profiles from other breeds, which might result from the environmental and nutritional management applied and the natural deficiency of nitrogen, phosphorus and calcium in the region's pastures.(AU)

Nelore é a segunda maior raça bovina do mundo e tem participado ativamente da expansão das novas fronteiras agrícolas brasileiras. Nesse contexto, o objetivo do presente estudo foi determinar os intervalos de referência hematológicos e bioquímicos de matrizes Nelore criadas em regime extensivo sem suplementação, ao longo do sudoeste do estado do Piauí. Amostras de sangue foram coletadas de 55 fêmeas multíparas da raça Nelore. Os parâmetros bioquímicos e hematológicos foram analisados por método estatístico paramétrico com IC 95% para os limites de referência. Os valores médios de hemácias, hemoglobina e índices hematimétricos apresentaram intervalos de referência semelhantes aos padrões de referência. Tanto o hematócrito quanto os granulócitos e os agranulócitos apresentaram alterações típicas de animais criados em ambientes com temperaturas mais elevadas. Os perfis mineral, enzimático, proteico e metabólico foram semelhantes aos de outras raças bovinas, mas com uma faixa de valores mais estreita. No entanto, valores médios mais baixos foram observados para os níveis de cálcio ionizado, proteína total e ureia. Fêmeas Nelore apresentam perfis bioquímicos e hematológicos ligeiramente diferentes de outras raças, o que pode resultar dos manejos ambiental e nutricional aplicados e da deficiência natural de nitrogênio, fósforo e cálcio nas pastagens da região.(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.

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)

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.

Is it time to restrict the clinical use of dipyrone? / ¿Es tiempo de restringir el uso clínico de la dipirona?

Dipyrone (or metamizole) is an analgesic and antipyretic for oral or parenteral administration. Its action mechanism is directly related to the inhibition of the signaling of TRPA1 (Transient Receptor Potential Ankirin 1). The TRPA1 ion channel, located in the plasma membrane of a subpopulation of nociceptors, plays a major role in pain transmission.1-3 However, the clinical use of dipyrone is associated with various adverse effects such as agranulocytosis, aplastic anemia, anaphylaxis, toxic epidermal necrolysis, renal failure, upper gastrointestinal tract bleeding, induction of acute attacks of porphyria, among others.4-7 One study also reported an increased risk of leukemia in children born to mothers who took dipyrone during pregnancy.

La dipirona (o metamizol) es un analgésico y antipirético para administración oral o parenteral. Su mecanismo de acción está directamente relacionado con la inhibición de la señalización de TRPA1 (Transient Receptor Potential Ankirin 1). El canal de iones TRPA1, localizado en la membrana plasmática de una subpoblación de nocioceptores, tiene una función primordial en la transmisión del dolor.1­3 Sin embargo, el uso clínico de la dipirona se asocia a diversos efectos adversos como agranulocitosis, anemia aplástica, anafilaxia, necrolisis epidérmica tóxica, insuficiencia renal, sangrado de tracto gastrointestinal superior, inducción de ataques agudos de porfiria, entre otros.4­7 Un estudio reportó también un incremento en el riesgo de leucemia en niños nacidos de madres que consumieron dipirona durante el embarazo.

Methimazole-induced aplastic anemia with concomitant Hepatitis in a young Filipina with Graves' disease / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">A 34-year-old Filipino with Graves' disease on methimazole came in due to fever, sore throat and jaundice. Patient was initially diagnosed with methimazole induced agranulocytosis and drug induced liver injury. She was treated with intravenous broad spectrum antibiotic and granulocyte colony stimulating factor. On day 4 of admission, patient had pancytopenia and was managed as methimazole induced aplastic anemia and was started on steroid therapy and 1 unit of packed red blood cell was transfused. The jaundice also increased hence she was given ursodeoxycholic acid. On day 9 of admission, with the consideration of "lineage steal phenomenon," biopsy was done and eltrompobag was started. Patient was discharged stable at 12th day of hospital admission. This case presents the 3 rarest, life threatening complication of methimazole: agranulocytosis, aplastic anemia and hepatitis. </p>

Is it necessary to take anthelmintics every year in Korea?

Is it necessary to intake anthelmintics every year in Korea? To answer to this question, the recent nation-wide egg positive rate of the intestinal nematodes in Korea was presented. The anthelminthics which are purchasable without physician's prescription were also introduced with their pharmacological reaction and indication. The egg positive rate of Ascaris lumbricoides in 2012 was 0.025%. Those of Trichuris trichiura and Enterobius vermicularis were 0.27% and 0.004%, respectively. In 2018, purchasable anthelmintics without physician's prescription in Korea were albendazole and flubendazole only. Those two anthelmintics were derivatives of benzimidazole that may cause some side effects such as hepatitis, increase of hepatic enzymes, granulocytopenia, or pancytopenia. These anthelmintics showed excellent effect to ascariasis; while, they are not sufficient to treat trichuriaiss. For treatment of enterobiasis, repeated taking 3 times with 3 weeks interval and mass treatment of the family of egg positive person are required. In conclusion, it is not necessary to take anthelmintics every year without specific diagnosis because of negligible egg positive rate of intestinal nematodes and complicated therapeutic module for enterobiasis. There was no specific symptom of ascariasis or trchuriasis if worm burden is not high. The common symptoms of enterobiasis were pain or itching at the perianal area, sleep difficulty, or diarrhea. If intestinal nematode infection is suspected, stool examination or perianal swab should be done before prescribing anthelmintics.

Quetiapine Induced Autoimmune Hemolytic Anemia in a Child Patient: A Case Report

Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient's own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.

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.

Conversion of primary hypothyroidism to hyperthyroidism:A case report / Journal of the ASEAN Federation of Endocrine Societies

@#A 51-year-old Caucasian male developed Graves’ thyrotoxicosis following long-standing treatment for hypothyroidism. After a short period of treatment with carbimazole, he developed agranulocytosis and required total thyroidectomy. In this relevant case report, we review several pathogenetic mechanisms that explain the transformation of autoimmune hypothyroidism into Graves’ disease and the possible approaches to the management of agranulocytosis secondary to antithyroid medications. Further studies are required to determine the best way to manage severe thyrotoxicosis when agranulocytosis develops due to antithyroid medications.

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.

Neutropenia inducida por citostáticos en oncología / Neutropenia induced by cytostatics in oncology

Se realizó un estudio descriptivo y transversal de 330 pacientes con cáncer, atendidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde junio hasta diciembre del 2014, para determinar la presencia de neutropenias inducidas por quimioterapia. Presentaron esa afección 145 pacientes (44,0 por ciento). Predominaron el grupo etario de 41-60 años (51,0 por ciento), el sexo femenino (87,5 por ciento), el cáncer de mama (64,8 por ciento), el estadio clínico II (50,3 por ciento), los afectados con 2 episodios de neutropenia (62,1 por ciento), así como los grados leve (51,7 por ciento) y moderado (37,9 por ciento). Respondieron al tratamiento con ior® LeukoCIM 118 pacientes (81,4 por ciento). No se estableció asociación entre las diferentes combinaciones de citostáticos, el número de episodios y los grados de esa enfermedad. La disponibilidad del ior® LeukoCIM para tratar dicha afección facilitará su uso profiláctico y mejorará la calidad de vida de estos pacientes

A descriptive and cross-sectional study of 330 patients with cancer, assisted in Conrado Benítez Oncological Hospital in Santiago de Cuba, was carried out from June to December, 2014, to determine the presence of neutropenias induced by chemotherapy. This disorder was present in 145 patients (44.0 percent). There was a prevalence of the 41-60 age group (51.0 percent), female sex (87.5 percent), breast cancer (64.8 percent), clinical stage II (50.3 percent), those affected patients with 2 neutropenia episodes (62.1 percent), as well as light (51.7 percent) and moderate grades (37.9 percent). One hundred eighteen patients responded to the treatment with ior® LeukoCIM (81.4 percent). There was no association between the different combinations of cytostatics, number of episodes and grades of that disease. The availability of the ior® LeukoCIM to treat this disorder will facilitate its prophylactic use and will improve these patients life quality

Efectos adversos severos del Metimazol. Comunicación de dos casos y revisión de la literatura / Severe adverse effects of Methimazole. Communication of two cases and review of the literature

Los fármacos antitiroideos constituyen uno de los pilares del tratamiento del hipertiroidismo. En nuestro país solo se encuentra disponible el metimazol. Estas drogas han sido asociadas a múltiples reacciones adversas, la mayoría leves. Efectos adversos infrecuentes pero potencialmente letales como la agranulocitosis, hepatitis y el síndrome de artritis por antitiroideos, obligan a suspender el tratamiento. Comunicamos dos casos de complicaciones infrecuentes del tratamiento con metimazol.

Antithyroid drugs are one of the cornerstones in the management of hyperthyroidism. In our country, only methimazole is available. These drugs have been related to a variety of adverse reactions, most of them minor. Infrequent but potentially lethal side effects such as agranulocytosis, hepatitis and the antithyroid arthritis syndrome, demand drug cessation. We report two cases of infrequent complications of methimazole.

Neutropenia with Multiple Antipsychotics Including Dose Dependent Neutropenia with Lurasidone

Antipsychotic-induced agranulocytosis is a significant side effect that is known to occur with most of the antipsychotic medications. It usually resolves once the medications are stopped and patients are able to be switched over to another antipsychotic medication. Lurasidone has not been reported to cause leukopenia and neutropenia. This case report is of a patient with a past history of risperidone induced-aganulocytosis developing dose related leukopenia and neutropenia with lurasidone.

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.