Anormalidades hematológicas en enfermedad hepática, fisiopatología y consideraciones terapéuticas / Hematologic disorders in liver failure: pathophysiology and therapeutic considerations

RESUMEN Las alteraciones en los recuentos celulares sanguíneos representan los hallazgos clínicos más notorios y recurrentes en pacientes que padecen enfermedad hepática, tanto aguda como crónica. Estos cambios constituyen un marcador importante de la disfunción hepática y, a menudo, desempeñan un papel crucial en la evaluación y manejo de estos pacientes. En conjunto con el alargamiento de las pruebas de coagulación, la trombocitopenia es la irregularidad más prevalente en estos individuos. Esta condición, así como las leucopenias, se le atribuye en gran medida al hiperesplenismo, una alteración en la que el bazo retiene y destruye las células sanguíneas, incluidas las plaquetas. Sin embargo, cuando el conteo plaquetario desciende por debajo de 10 x 103/µl, es fundamental considerar otras causas, como factores autoinmunitarios que pueden estar contribuyendo con la trombocitopenia. La anemia, definida como una disminución en el número de glóbulos rojos o en los niveles de hemoglobina, es otra característica constante que acompaña a la enfermedad hepática. Aunque en la mayoría de los casos la anemia es macrocítica, en algunas situaciones puede ser secundaria a eventos hemolíticos, como lo observado en el síndrome de Zieve. Esta diversidad en las manifestaciones de la anemia en pacientes hepáticos subraya la complejidad de las interacciones entre el hígado y los componentes sanguíneos. A pesar de los avances en la comprensión de las causas subyacentes de estas citopenias, las opciones del tratamiento siguen siendo limitadas. Generalmente, las opciones terapéuticas se enfocan en la administración de transfusiones de hemocomponentes para compensar las deficiencias en los recuentos celulares o en el uso de análogos de trombopoyetina (TPO) para estimular temporalmente la producción de las plaquetas en la medula ósea. No obstante, estos tratamientos tienden a abordar los síntomas más que las causas fundamentales de las alteraciones hematológicas en la enfermedad hepática. La persistencia y el empeoramiento de estas alteraciones pueden servir como indicadores tempranos de la progresión de la disfunción hepática. La relación intrincada entre el hígado y la homeostasis hematológica continúa siendo objeto de investigación, la compresión más profunda de estos mecanismos podría abrir potencialmente la puerta hacia enfoques terapéuticos más específicos y efectivos para abordar las citopenias en el contexto de la enfermedad hepática.

ABSTRACT Alterations in blood cell counts are the most prominent and recurrent clinical findings among patients suffering from both acute and chronic liver disease. These changes are an important marker of liver failure and often play a key role in the evaluation and management of these patients. Together with the prolongation of coagulation tests, thrombocytopenia is the most common disorder among these individuals. This condition, as well as leukopenia, is largely attributable to hypersplenism, a disorder in which the spleen retains and destroys blood cells, including platelets. However, when the platelet count drops below 10x103/µl, it is essential to consider other causes, such as autoimmune factors that may be contributing to the development of thrombocytopenia. Anemia, defined as a decrease in red blood cell count or hemoglobin levels, is another common characteristic of liver disease. Although in most cases macrocytic anemia occurs, in some situations it can be secondary to hemolytic events, as observed in Zieve's syndrome. This wide range of manifestations of anemia among liver patients highlights the complex interaction between liver and blood components. Despite advances in understanding the underlying causes of these cytopenias, treatment options remain limited. Therapeutic options generally focus on the transfusion of blood products to compensate for deficiencies in cell counts or on the use of thrombopoietin (TPO) analogues to temporarily stimulate platelet production in the bone marrow. However, these treatments tend to address the symptoms rather than the root causes of hematologic disorders in liver disease. The persistence and worsening of these disorders may serve as early indicators of the progression of liver failure. The complicated relationship between liver and hematological homeostasis remains the subject of research. A deeper understanding of these mechanisms could potentially open the door toward more targeted and effective therapeutic approaches to address cytopenias in the context of liver disease.

Mielopatía por déficit de cobre: serie de casos y revisión de la literatura / Myelopathy due to copper deficiency: A case series and review of the literature

El déficit de cobre puede presentarse como una mielopatía y manifestarse como una ataxia sensorial secundaria a una desmielinización de los cordones posteriores de la médula espinal. Puede acompañarse de citopenias, principalmente anemia y leucopenia. Se presenta una serie de casos de tres pacientes con mielopatía por déficit de cobre, diagnosticados y manejados desde el año 2020 al 2022 en un hospital universitario de alta complejidad en Colombia. Dos de los casos eran mujeres. El rango de edad fue entre 57 y 68 años. En los tres casos, los niveles séricos de cobre estaban disminuidos y en dos de ellos, se descartaron diferentes causas de mielopatía que afectan los cordones posteriores de la médula espinal como el déficit de vitamina B12, vitamina E y ácido fólico, tabes dorsal, mielopatía por virus de la inmunodeficiencia humana, esclerosis múltiple e infección por el virus linfotrópico humano de tipo I y II, entre otras. Sin embargo, un paciente tenía deficiencia de vitamina B12 asociada con de cobre en el momento del diagnóstico de la mielopatía. En los tres casos hubo ataxia sensitiva y en dos, la paraparesia fue el déficit motor inicial. Se deben incluir siempre la determinación de los niveles de cobre dentro del abordaje diagnóstico de todo paciente con enfermedad gastrointestinal crónica, con diarrea crónica, síndrome de mala absorción o reducción significativa de la ingestión en la dieta, y que desarrolle síntomas neurológicos sugestivos de compromiso de los cordones, ya que se ha reportado que el retraso en el diagnóstico de las mielopatías se asocia con pobres desenlaces neurológicos.

Copper deficiency can present as myelopathy by the manifestation of sensory ataxia, secondary to demyelination of the posterior cords of the spinal cord, accompanied by cytopenia, mainly anemia, and leukopenia. Case series study of three patients with myelopathy due to copper deficiency, diagnosed and managed from 2020 to 2022 in a highly complex university hospital in Colombia. Regarding gender, two cases were female patients. The age range was between 57 and 68 years. In all three cases serum copper levels were decreased, and in two of these, different causes of myelopathy affecting the posterior cords of the spinal cord were ruled out, such as vitamin B12, vitamin E and folic acid deficiency, tabes dorsalis, myelopathy due to human immunodeficiency virus, multiple sclerosis and infection by the human lymphotropic virus type I and II, among others. However, at the moment of the myelopathy diagnosis, one patient had vitamin B12 deficiency associated with copper insufficiency. All three cases presented sensory ataxia, and in two, paraparesis was the initial motor deficit. The diagnostic approach must include copper levels assessment in every case of patients with chronic gastrointestinal pathology, chronic diarrhea, malabsorption syndrome, or significant reduction in dietary intake; and the development of neurological symptoms that may suggest cord involvement. It has been reported that a delay in diagnosis can lead to poor neurological outcomes.

Perfil hematológico de idoso com dengue internado em unidade de terapia intensiva / Hematological profile of elderly people with dengue hospitalized in an intensive care unit / Perfil hematológico de ancianos con dengue hospitalizados en una unidad de cuidados intensivos

Introdução: A dengue é considerada a arbovirose mais comum no mundo, sendo hoje um problema crescente de saúde pública. Objetivo: Por ser considerada de alta prevalência, foi realizada a avaliação hematológica de um paciente hospitalizado na Unidade de Terapia Intensiva na cidade de Umuarama-PR. Metodologia: Tratou-se de um estudo descritivo retrospectivo, do qual foram analisados os resultados de hemogramas obtidos por um laboratório local, considerando que o paciente constava como sorologia positiva para NS1. Foram avaliados 09 laudos de hemograma emitidos durantes 5 dias de internamento do paciente. Os resultados foram comparados entre os laudos e com os valores de referência disponibilizados pelo próprio laudo. Resultados: Com base na análise dos hemogramas pode-se verificar a redução do hematócrito em 33,33%, macrocitose em 88,9%, leucopenia em 27,3%, trombocitopenia em 27,3%. Conclusão: Conclui-se que através dos laudos avaliados foram encontrados plaquetopenia, leucopenia, linfocitopenia, eosinopenia, neutropenia, monocitopenia. Evidenciando o hemograma como uma ferramenta laboratorial de grande auxílio na avaliação do paciente.

Introduction: Dengue is considered the most common arbovirus in the world, and is now a growing public health problem. Objective: Due to its high prevalence, a hematological evaluation of a patient hospitalized in the Intensive Care Unit in the city of Umuarama-PR was carried out. Methodology: This was a retrospective descriptive study, in which the results of blood counts obtained by a local laboratory were analyzed, considering that the patient had positive serology for NS1. 09 blood count reports issued during the 5 days of the patient's hospitalization were evaluated. The results were compared between the reports and with the reference values provided by the report itself. Results: Based on the analysis of blood counts, it was possible to verify a reduction in hematocrit in 33.33%, macrocytosis in 88.9%, leukopenia in 27.3%, thrombocytopenia in 27.3%. Conclusion: It is concluded that through the evaluated reports, thrombocytopenia, leukopenia, lymphocytopenia, eosinopenia, neutropenia, monocytopenia were found. Evidencing the blood count as a laboratory tool of great help in the evaluation of the patient.

Introducción: El dengue es considerado el arbovirus más común en el mundo, y actualmente es un problema creciente de salud pública. Objetivo: Debido a su alta prevalencia, se realizó una evaluación hematológica de un paciente hospitalizado en la Unidad de Cuidados Intensivos de la ciudad de Umuarama-PR. Metodología: Se trató de un estudio descriptivo retrospectivo, en el cual fueron analizados los resultados de los hemogramas obtenidos por un laboratorio local, considerando que el paciente tenía serología positiva para NS1. Fueron evaluados 09 informes de hemogramas emitidos durante los 5 días de internación del paciente. Los resultados se compararon entre los informes y con los valores de referencia proporcionados por el propio informe. Resultados: A partir del análisis de los hemogramas, fue posible verificar reducción del hematocrito en 33,33%, macrocitosis en 88,9%, leucopenia en 27,3%, trombocitopenia en 27,3%. Conclusiones: Se concluye que a través de los reportes evaluados se encontró trombocitopenia, leucopenia, linfocitopenia, eosinopenia, neutropenia, monocitopenia. Evidenciando el hemograma como una herramienta de laboratorio de gran ayuda en la evaluación del paciente.

Síndrome de plaquetas grises y embarazo: reporte de un caso y revisión de la bibliografía / Grey platelet syndrome and pregnancy: case report and literature review

Resumen ANTECEDENTES: Las repercusiones del embarazo en el síndrome de plaquetas grises no están definidas, la bibliografía reporta pocos casos; por tanto, los desenlaces no son muy conocidos. OBJETIVO: Describir el caso de una paciente con síndrome de plaquetas grises y embarazo para proponer pautas de atención y recomendaciones para el seguimiento antenatal, peri y posparto en este grupo de pacientes. Además, revisar la bibliografía más reciente. CASO CLÍNICO: Paciente primigesta de 29 años, con diagnóstico de trombocitopenia a partir de los 6 años. Durante el embarazo se consideró de origen genético por lo que se solicitó el exoma clínico que reportó una variante en el gen NBEAL2 c 7244G>T p G1y2415Val homocigoto, con diagnóstico de síndrome de plaquetas grises. Permaneció en seguimiento en los servicios de Hematología y Obstetricia, sin complicaciones mayores; cerca del parto requirió transfusión de plaquetas. A las 39 semanas de embarazo ingresó para atención del parto, se dio prueba de trabajo de parto; sin embargo, por indicación obstétrica (detención de la dilatación) se decidió la finalización mediante cesárea. METODOLOGÍA: Se revisaron las bases de datos de PubMed, LILACS, Medline, Clinical trials de los últimos 20 años. Los MeSH de búsqueda fueron "grey platelet" "syndrome" "pregnancy". Se encontraron 11 artículos de los que se descartaron 2 por estar fuera del rango de tiempo, un artículo duplicado y otros excluían embarazadas. En total se revisaron 9 artículos. CONCLUSIÓN: Este caso muestra que las mujeres con síndrome de plaquetas grises, si son debidamente acompañadas por un equipo interdisciplinario con experiencia pueden tener un embarazo y parto seguros.

Abstract BACKGROUND: The repercussions of pregnancy in grey platelet syndrome are undefined, with few cases reported in the literature; therefore, outcomes are not well known. OBJECTIVE: To describe the case of a patient with grey platelet syndrome and pregnancy in order to propose care guidelines and recommendations for antenatal, peri- and postpartum follow-up in this group of patients. In addition, to review the most recent literature. CLINICAL CASE: A 29-year-old primigravida patient diagnosed with thrombocytopenia since the age of 6. During pregnancy it was considered to be of genetic origin, so the clinical exome was requested, which reported a variant in the NBEAL2 c 7244G>T p G1y2415Val homozygous gene, with a diagnosis of grey platelet syndrome. She remained under follow-up in the haematology and obstetrics departments, without major complications; close to delivery she required platelet transfusion. At 39 weeks of pregnancy, she was admitted for delivery care, proof of labour was given; however, due to obstetric indications (arrest of dilatation) it was decided to terminate the pregnancy by caesarean section. METHODOLOGY: The databases of PubMed, LILACS, Medline, Clinical trials of the last 20 years were reviewed. The MeSH search terms were "grey platelet" "syndrome" "pregnancy". Eleven articles were found of which two were discarded for being out of time range, one article duplicated and others excluded pregnant women. In total 9 articles were reviewed. CONCLUSION: This case shows that women with grey platelet syndrome, if properly supported by an experienced interdisciplinary team, can have a safe pregnancy and delivery.

Acute intoxication with single oral dose of ochratoxin A (OTA) causes leukopenia, heteropenia, lymphopenia and lymphoid depletion in the bursa of Fabricius in broiler chicks / Intoxicação aguda com dose oral única de ocratoxina A (OTA) causa leucopenia, heteropenia, linfopenia e depleção linfoide na bolsa de Fabricius em pintainhos de corte

Ochratoxin A (OTA) is a mycotoxin produced by species of Penicillium and Aspergillus, agricultural product contaminants. Chronic and sub-chronic OTA intoxication by chickens ingesting contaminated feed, leads to health damages due to its hepatotoxic, nephrotoxic, cytotoxic, immunotoxic, gastrotoxic, and possibly carcinogenic effects. As there are few data on acute intoxication, the present study evaluated the effects of a single acute OTA intoxication dose on immunological and hematological parameters in chicks. Sixteen one-day-old chicks were used, separated into two groups (n=8). A single dose of OTA (1400 µg kg-1 body weight) was administered, via gavage, for the OTA group and one dose of sterile PBS for the control group. On the 13th day, blood samples were collected to assess hematological and biochemical parameters, and on the 14th day, euthanasia and collection of lymphoid organs were performed. The animals of the OTA group demonstrated a significant decrease in total circulating leukocytes (p<0.001) with heteropenia (p<0.001) and lymphopenia (p=0.023), decrease hematocrit (p=0.020), hemoglobin (p=0.032), and plasma IgA (p =0.044), and increased plasma uric acid level (p=0.045), in relation to the control group. In addition, the animals intoxicated with OTA showed depletion of lymphoid cells in the bursa of Fabricius (p=0.016), but not in the thymus or spleen (p>0.05), compared to the control. For the other parameters: total plasma proteins, plasma IgY levels, and anti-Newcastle Disease Virus (NDV) vaccine titers from matrices, there were no significant differences between the analyzed groups (p>0.05), although there was a worsening tendency in contaminated animals. In conclusion, even a single acute OTA intoxication at a high dose, leads to the suppression of the systemic immune response, also affecting some hematological or biochemical parameters in chicks.

Ocratoxina A (OTA) é uma micotoxina produzida por espécies de Penicillium e Aspergillus, contaminantes de produtos agrícolas. Intoxicação crônica e subcrônica por OTA em frangos que ingerem ração contaminada, levam à danos à saúde devido aos seus efeitos hepatotóxicos, nefrotóxicos, citotóxicos, imunotóxicos, gastrotóxicos e possivelmente carcinogênicos. Como há poucos dados sobre intoxicação aguda, o presente estudo avaliou os efeitos de uma dose única de intoxicação aguda por OTA sobre parâmetros imunológicos e hematológicos em pintainhos. Foram utilizados 16 pintainhos de um dia de idade, separados em dois grupos (n=8). Uma dose única de OTA (1400 µg kg-1 de peso corporal) foi administrada, via gavagem, para o grupo OTA e uma dose de PBS estéril para o grupo controle. No 13º dia foram coletadas amostras de sangue para avaliação dos parâmetros hematológicos e bioquímicos, e no 14º dia foi realizada a eutanásia e coleta de órgãos linfoides. Os animais do grupo OTA demonstraram diminuição significativa do total de leucócitos circulantes (p<0,001) com heteropenia (p<0,001) e linfopenia (p=0,023), diminuição do hematócrito (p=0,020), hemoglobina (p=0,032) e IgA plasmática (p=0,044) e aumento do nível plasmático de ácido úrico (p=0,045), em relação ao grupo controle. Além disso, os animais intoxicados com OTA apresentaram depleção de células linfóides na bolsa de Fabricius (p=0,016), mas não no timo ou baço (p>0,05), em relação ao controle. Para os demais parâmetros: proteínas totais do plasma, níveis plasmáticos de IgY e títulos de vacinas contra o Vírus da Doença de Newcastle (NDV) das matrizes, não houve diferenças significativas entre os grupos analisados (p>0,05), embora tenha havido uma tendência de piora nos animais contaminados. Em conclusão, mesmo uma intoxicação única aguda por OTA em alta dose, leva à supressão da resposta imune sistêmica, afetando também alguns parâmetros hematológicos ou bioquímicos em pintainhos.

Asociación entre la variación de glóbulos blancos y las manifestaciones clínicas, anticuerpos e infecciones en adultos con lupus eritematoso sistémico / White blood cells count variation in systemic lupus erythematosus: its association to disease manifestations, antibodies and risk of infections

Introducción: la asociación de leucopenia, linfopenia y neutropenia con la presencia de autoanticuerpos, manifestaciones clínicas e infecciones en pacientes con lupus eritematoso sistémico (LES) no está bien establecida. Los objetivos de este estudio fueron analizar los cambios en los recuentos de leucocitos y linfocitos en pacientes con LES y su asociación con manifestaciones clínicas, autoanticuerpos y riesgo de infecciones. Materiales y métodos: se recolectaron retrospectivamente los valores de leucocitos, linfocitos y neutrófilos. Se agruparon a los pacientes en cinco categorías: recuento de glóbulos blancos normales, leucopenia (persistente o intermitente) y linfopenia (persistente o intermitente). Se registraron las manifestaciones clínicas, los autoanticuerpos acumulados, el daño, la mortalidad, las infecciones y los tratamientos inmunosupresores recibidos de cada paciente. Resultados: se incluyeron 89 pacientes. La linfopenia (89%) fue la anormalidad más frecuente. La leucopenia intermitente y la persistente se detectaron en el 44% y en el 11% de los pacientes, respectivamente. La linfopenia intermitente y la persistente se hallaron en el 44% y en el 45% de los casos. En el análisis univariado, la presencia de rash discoide se asoció a leucopenia (20,4 vs. 5,1; p=0,059) y el tratamiento con mofetil micofenolato a un recuento normal de leucocitos (p=0,046). El compromiso neurológico se asoció a recuento normal de linfocitos (22,2% vs. 0% y 7,5%; p=0,027); los pacientes con anti-RNP (anti ribonucleoproteína nuclear) presentaron más frecuentemente linfopenia persistente (47% vs. 15,4% y 20%; p=0,007). Ninguno de los grupos se asoció a una mayor prevalencia de infecciones. En el análisis multivariado, el mofetil micofenolato se asoció negativamente a leucopenia (OR 0.33 IC 95% 0,1-0,9; p=0,042) y el compromiso neurológico se asoció negativamente a linfopenia (OR 0.08; p=0,022). Conclusiones: en el análisis univariado, el rash discoide se asoció a leucopenia y el anti-RNP a linfopenia. Al ajustar por otras variables significativas, el tratamiento con mofetil micofenolato se asoció a un recuento normal de leucocitos, mientras que las manifestaciones neurológicas se relacionaron a linfocitos normales. No se demostró asociación de las infecciones con ninguno de los grupos.

Introduction: leukopenia, lymphopenia and neutropenia association to clinical manifestations and infections in systemic lupus erythematosus (SLE) is not well defined. The objectives were to analize leucocytes and lymphocytes variations in SLE patients and their association to clinical manifestations, autoantibodies and infections risk. Materials and methods: total white blood cell (WBC) count, lymphocyte, and neutrophils counts were collected retrospectively. Data were grouped into normal WBC cell count, persistent or intermittent leucopenia and lymphopenia. Disease manifestations, accumulated autoantibodies, damage, mortality, infections and immunosuppressants ever received were registered. Results: study sample included 89 patients. Lymphopenia (89%) was the most common abnormality. Intermittent and persistent leukopenia were detected in 44% and 11% cases. Intermittent and persistent lymphopenia were found in 44% and 45% cases. In univariate analysis, discoid rash was associated to leukopenia (20.4 vs 5.1 p=0.059) and mycophenolate treatment to normal leukocyte count (p=0.046). Patients with neurological disorder tended to have normal lymphocyte counts rather than intermittent or persistent lymphopenia (22.2% vs 0% and 7.5% p=0.027); patients with anti-RNP tended to belong to the persistent lymphopenia group (47% vs 15.4% and 20% p=0.007). Infections were not associated to any of the categories. In multivariate analysis mycophenolate was negatively associated to leukopenia (OR 0.33 95% CI 0.1-0.9 p=0.042) while neurological disorder was negatively associated to lymphopenia (OR 0.08 p=0.022). Conclusions: in univariate analysis, discoid rash was associated to leukopenia and anti-RNP to lymphopenia. When adjusted to other significant variables, mycophenolate was related to normal leukocyte while neurological manifestations were to normal lymphocyte counts. Infections were not associated to any of the categories.

Alterações hematológicas na dengue grave ­ uma revisão sistemática / Hematological changes in serious dengue ­ a systematic review

A infecção causada pelo vírus da dengue gera quase 400 milhões de novos casos a cada ano especialmente nos países tropicais e subtropicais, sendo considerada um problema de saúde pública em todo o mundo. Trata-se de uma doença sistêmica e infectocontagiosa, que pode ser classificada como dengue com ou sem sinais de alarme, e dengue grave. As alterações hematológicas estão relacionadas com a gravidade da doença e direcionam condutas médicas. Neste estudo foram realizadas buscas nas plataformas CAPES, LILACS e PubMed no período de janeiro de 2014 a janeiro de 2021 com o objetivo de reunir e avaliar artigos publicados que traziam informações sobre as alterações hematológicas na infecção de dengue grave. Após revisão minuciosa, foram incluídos no estudo um total de 15 artigos e os principais dados observados foram: diminuição da contagem de plaquetas (66,7%), aumento do hematócrito (26,6%), aumento do tempo de tromboplastina parcial ativada (26,6%) e leucopenia (26,6%).

The infection caused by the dengue virus generates almost 400 million new cases each year, especially in tropical and subtropical countries, being considered a public health problem worldwide. It is a systemic and infectious disease, which can be classified as dengue with or without alarm signs, and severe dengue. Hematological changes are related to the severity of the disease and may guide medical procedures. In this study, researches were carried out on the CAPES, LILACS and PubMed platforms with the aim of gathering and evaluating published articles that brought information about hematological changes in severe dengue infection from January 2014 to January 2021. After thorough review, a total of 15 articles were included in the study and the main data observed were: decreased platelet count (66.7%), increased hematocrit (26.6%), increased activated partial thromboplastin time (26.6%) and leukopenia (26.6%).

Hematological and histopathological changes in medular aplasia resulting from Ehrlichia canis infection in a Border collie dog / Alterações hematológicas e histopatológicas na aplasia medulardecorrente da infecção por Ehrlichia canis em cão da raça Border Collie

The Canine Monocytic Ehrlichiosis (CME) is an infectious disease that commonly affects dogs of all breeds and ages. It is caused by the bacterium Ehrlichia canis and is transmitted by the tick Rhipicephalus sanguineus. The disease may pre-sent itself in the acute, subclinical, and chronic forms. The present study reports the case of a 2-year-old male Border Collie with advanced stage CME, attended at the Pet Clinic of the Veterinary Hospital of the University Federal de Jataí, which resul-ted in medullary aplasia. The diagnosis of marrow aplasia was based on the necroscopic and histopathological examinations. At necropsy, the diaphyses of the long bones were filled with diffuse, strongly whitish and pasty tissue, typical of the adipose tissue, also found in the femoral epiphyses. The histopathology showed unilocular adipose tissue as the major constituent of the bone marrow and rare islands of marrow cells. These findings were compatible with severe hypoplasia of the red bone mar-row and hyperplasia of the white bone marrow, affecting hematopoiesis, resulting in the laboratory alterations observed in the hematocrit, WBC, and plateletogram.(AU)

A erliquiose monocítica canina (EMC) é uma doença infecciosa que comumente afeta cães de todas as raças e idades. Causada pela bactéria Ehrlichia canis e transmitida pelo carrapato Rhipicephalus sanguineus, a doença pode apresentar-se nas for-mas aguda, subclínica e crônica. O presente trabalho relata o caso de um cão, raça Border Collie, macho, 2 anos de idade, com EMC em estágio avançado, atendido no Setor de Clínica de Animais de Companhia do Hospital Veterinário da Universidade Federal de Jataí, caso este que resultou em aplasia medular. O diagnóstico da aplasia de medula baseou-se na realização de exames necroscópico e histopatológico. Na necropsia verificou-se a diáfise de ossos longos preenchida por tecido difuso, seve-ramente esbranquiçado e pastoso, característico de tecido adiposo, também encontrado em epífises femorais. No histopatoló-gico foi verificado tecido adiposo unilocular como maior constituinte da medula óssea e raras ilhas de células medulares. Esses achados foram compatíveis com hipoplasia severa de medula óssea vermelha e hiperplasia de medula óssea branca, afetando a hematopoiese resultando nas alterações laboratoriais verificadas no eritrograma, leucograma e plaquetograma.(AU)

Hematological and histopathological changes in medular aplasia resulting from Ehrlichia canis infection in a Border collie dog / Alterações hematológicas e histopatológicas na aplasia medulardecorrente da infecção por Ehrlichia canis em cão da raça Border Collie

The Canine Monocytic Ehrlichiosis (CME) is an infectious disease that commonly affects dogs of all breeds and ages. It is caused by the bacterium Ehrlichia canis and is transmitted by the tick Rhipicephalus sanguineus. The disease may pre-sent itself in the acute, subclinical, and chronic forms. The present study reports the case of a 2-year-old male Border Collie with advanced stage CME, attended at the Pet Clinic of the Veterinary Hospital of the University Federal de Jataí, which resul-ted in medullary aplasia. The diagnosis of marrow aplasia was based on the necroscopic and histopathological examinations. At necropsy, the diaphyses of the long bones were filled with diffuse, strongly whitish and pasty tissue, typical of the adipose tissue, also found in the femoral epiphyses. The histopathology showed unilocular adipose tissue as the major constituent of the bone marrow and rare islands of marrow cells. These findings were compatible with severe hypoplasia of the red bone mar-row and hyperplasia of the white bone marrow, affecting hematopoiesis, resulting in the laboratory alterations observed in the hematocrit, WBC, and plateletogram.

A erliquiose monocítica canina (EMC) é uma doença infecciosa que comumente afeta cães de todas as raças e idades. Causada pela bactéria Ehrlichia canis e transmitida pelo carrapato Rhipicephalus sanguineus, a doença pode apresentar-se nas for-mas aguda, subclínica e crônica. O presente trabalho relata o caso de um cão, raça Border Collie, macho, 2 anos de idade, com EMC em estágio avançado, atendido no Setor de Clínica de Animais de Companhia do Hospital Veterinário da Universidade Federal de Jataí, caso este que resultou em aplasia medular. O diagnóstico da aplasia de medula baseou-se na realização de exames necroscópico e histopatológico. Na necropsia verificou-se a diáfise de ossos longos preenchida por tecido difuso, seve-ramente esbranquiçado e pastoso, característico de tecido adiposo, também encontrado em epífises femorais. No histopatoló-gico foi verificado tecido adiposo unilocular como maior constituinte da medula óssea e raras ilhas de células medulares. Esses achados foram compatíveis com hipoplasia severa de medula óssea vermelha e hiperplasia de medula óssea branca, afetando a hematopoiese resultando nas alterações laboratoriais verificadas no eritrograma, leucograma e plaquetograma.

Caracterización de la plaquetopenia, leucopenia y aumento del hematocrito en la evolución y gravedad de los pacientes con diagnóstico de dengue / Characterization of thrombocytopenia, leukopenia and increased hematocrit in the evolution and severity of patients with dengue diagnosis

El virus del dengue (DENV) ha frecuentado nuestro planeta por más de tres siglos. La picadura del Aedes aegypti causa el DENV. El diagnóstico clínico y laboratorial son importantes para el manejo del dengue. Objetivo: caracterizar la presencia de la plaquetopenia, leucopenia y aumento del hematocrito con la evolución y gravedad de los pacientes con Dengue, en el Hospital Univalle, en la ciudad de Cochabamba, Bolivia. Material y métodos: estudio retrospectivo, longitudinal y analítico, desde el 2017 al 2020. Resultados: se identificaron 235 pacientes, 83% el 2020; el 65% entre 19 a 45 años; 54% de sexo masculino, 80% provienen de Cercado-Cochabamba, siendo más del 95% de la zona sud. La prueba de detección de la proteína NS1Ag (AccuBio Tech Co, Ltd.) se usó en 71%; 56% se hospitalizaron; más del 50% presentaron sintomatología entre el 2do y 5to día. Dentro la clasificación del dengue, el 75% perteneció a dengue sin signos de alarma (p= 45% en varones, presentando más de 5 días de hospitalización (p=0,023). Conclusiones: plaquetopenia, leucopenia y el aumento del hematocrito son biomarcadores de severidad clínica y estancia hospitalaria, asociados a un diagnóstico precoz, empleando la sintomatología y pruebas rápidas disponibles; siendo necesario considerar la presencia de pacientes autóctonos de la zona sud de Cochabamba, Cercado.

Dengue virus (DENV) has haunted our planet for more than three centuries. The Aedes aegypti bite causes DENV. Clinical and laboratory diagnosis are important for the management of dengue. Objective: to characterize the presence of plaquetopenia, leukopenia and increased hematocrit with the evolution and severity of patients with Dengue, Hospital Univalle. Material and methods: retrospective, longitudinal and analytical study, 2017 to 2020. Results: 235 patients were identified, 83% in 2020; 65% between 19 to 45 years old; the male sex with 54%. 80% come from Cercado-Cochabamba, of these more than 95% from the southern area. The test with the detection of the NS1Ag protein (AccuBio Tech Co, Ltd.) was used in 71%; 56% were hospitalized; more than 50% presented symptoms between the 2nd and 5th day; Within the dengue classification, 75% belonged to dengue without warning signs (p = 45% in men and represented more than 5 days of hospitalization (p = 0,023). Conclusions: Plaquetopenia, leukopenia and increased hematocrit are biomarkers of clinical severity, hospital stay, associated with an early diagnosis, using the symptoms and rapid tests available; finally, consider the presence of autochthonous patients from the southern area of Cochabamba, Cercado.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor

ABSTRACT: This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p 0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.

RESUMO: Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p 0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.

Altas dosis de cobalamina y ácido fólico en el tratamiento de leucopenias post covid-19 / High doses of cobalamin and folic acid in post-covid-19 leukopenia treatment

Introducción: La leucopenia es una de las manifestaciones observadas en pacientes que padecieron COVID-19 y sus características son similares a las observadas en deficiencia de vitamina B12 y ácido fólico. Objetivo: Mostrar la utilidad de altas dosis de vitamina B12 y ácido fólico en el tratamiento de leucopenias post COVID-19. Métodos: Estudio descriptivo transversal de tipo retrospectivo. Se recolectó datos demográficos, clínicos y laboratoriales de pacientes (n=22) con leucopenia post COVID-19 que fueron tratados con dosis de vitamina B12 y ácido fólico. Se valoró seguimiento de datos clínicos y laboratoriales correspondientes tanto al diagnóstico como a las 4 y 8 semanas del tratamiento. Resultados: El cuadro de leucopenia se revirtió totalmente, los leucocitos incrementaron hasta alcanzar valores normales. Los niveles de hemoglobina incrementaron, aunque sin alcanzar valores normales. Si bien los linfocitos no presentaron disminución al diagnóstico, estos incrementaron manteniéndose dentro de parámetros normales. El VCM se mantuvo con leves modificaciones y las plaquetas no presentaron modificaciones. La sintomatología remitió a los 2 meses. Conclusiones: Los datos obtenidos pueden servir como parte de los fundamentos para el tratamiento del síndrome post COVID-19.

Introduction: Leukopenia is one of the persistent manifestations in patients who have suffered from COVID-19 and its characteristics are similar to those patients with vitamin B12 and folic acid deficiency. Objective: To show the usefulness high doses of vitamin B12 and folic acid in post COVID-19 leukopenia treatment. Material and methods: Retrospective descriptive cross-sectional study. Demographic, clinical and laboratory data were collected from patients (n = 22) with post COVID-19 leukopenia who were treated with doses of vitamin B12 and folic acid. Follow-up of clinical and laboratory data corresponding to diagnosis as well as 4 and 8 weeks after treatment was assessed. Results: Leukopenia was totally reversed, leukocytes increased and reached normal values. Hemoglobin levels increased, although without reaching normal values. Lymphocytes increased within normal parameters though they were not decreased at diagnosis. MCV levels remained with slight modifications, and platelets without modifications. Patients symptoms subsided after 2 months treatment. Conclusion: Data obtained can serve as part of treatment rationale in post-COVID-19 syndrome.

Prognostic values of physical and hematological parameters of dogs naturally infected with parvovirus PVC-2: retrospective study of 103 cases / [Valores prognósticos de parâmetros físicos e hematológicos de cães naturalmente infectados pelo parvovírus PVC-2: estudo retrospectivo de 103 casos]

Canine parvovirosis is a high mortality disease with acute clinical picture. However, there are few available resources to help stablish prognosis accurately. This study aimed to determine the prognostic threshold values for vital and hematological parameters of dogs naturally infected by the Carnivore protoparvovirus 1 (CPV). A retrospective study of 103 canine parvovirosis cases was carried out. Twenty seven percent of these (28/103) died, 96% (27/28) of which within the first four days of hospitalization. Deceased animals had significantly higher median values for heart (HR) and respiratory (f) rates, as well as significantly lower systolic blood pressure (SBP) than survivors. Severely leukopenic animals (<1,000 cells/µL), had a significantly higher mortality rate (68%, n=13) compared to that of other patients (P<0.0007). Animals with at least two of the following findings: severe hypotension (SBP< 90mmHg), tachycardia (HR > 150 bpm) and leukopenia, represented 34% (34/101) of the cases and had a survival rate of 29% (10/34), while animals with at most one of these parameters represented 66% (67/101) and had a survival rate of 94% (63/67). The presence of two or three abnormal parameters was significantly related to the higher death risk among dogs with parvovirosis (P<0.0001).(AU)

A parvovirose canina é uma doença de alta mortalidade e de quadro clínico agudo. No entanto, existem poucos recursos para se estabelecer prognóstico de maneira precisa. Este estudo objetivou analisar os valores prognósticos de parâmetros físicos e hematológicos de cães naturalmente infectados pelo Carnivore protoparvovirus 1 (CPV). Um estudo retrospectivo de 103 casos de parvovirose canina foi realizado. Desses, 27% dos animais (28/103) foram a óbito, sendo 96% (27/28) com ocorrência nos primeiros quatro dias de internamento. Os cães que foram a óbito apresentaram medianas das frequências cardíaca (FC) e respiratória (f) significativamente maiores e pressão arterial sistólica (PAS) consideravelmente menor que a dos sobreviventes. Entre os animais mais intensamente leucopênicos (<1.000 células/(L), a taxa de mortalidade (68%, n=13) foi expressivamente maior que a dos demais pacientes (P<0,0007). Os animais com hipotensão grave (PAS<90mmHg), taquicardia (FC>150bpm) e leucopenia intensa (leucometria<1.000 células/µL), ou duas dessas alterações clínicas, representaram 34% (34/101) dos casos e tiveram taxa de sobrevida de 29% (10/34), enquanto os animais com, no máximo, um desses parâmetros alterados representaram 66% (67/101) dos animais, com taxa de sobrevida de 94% (63/67). A presença de dois ou três parâmetros alterados esteve significativamente relacionada ao maior risco de óbito de cães com parvovirose (P<0,0001).(AU)

Trametinib and dabrafenib induced rhabdomyolysis, renal failure, and visual loss. Report of one case

ABSTRACT MEK- and BRAF-inhibitors trametinib and dabrafenib are successfully used for BRAF-mutated, metastasizing melanoma, but these compounds may induce side effects. We report a 50 years old female with BRAF-mutated metastasizing melanoma who received trametinib (2 mg/d) and dabrafenib (200 mg/d) after using interferon without benefit. Shortly after starting trametinib/dabrafenib, she experienced an inability to abduct the left eye. Eight days after starting this therapy the patient experienced loss of appetite, vomiting, diarrhea, vertigo, and fever of 40°C. Two days later she experienced visual loss, requiring permanent support for her daily activities. Two further days later myoglobinuria appeared in the absence of myalgias or muscle weakness but accompanied by marked tiredness and inactivity. She could not eat or drink during four days prior to admission. The patient suspected an adverse effect of trametinib/dabrafenib and discontinued it 2 days prior to admission. Thereafter, she experienced an almost complete remission of the deficits except for ocular muscle weakness and visual impairment.

Los inhibidores de MEX and BRAF como trametinib y dabrafenib se usan en el melanoma metastásico con mutación BRAF, pero pueden tener efectos secundarios. Informamos una paciente de 50 años con un melanoma metastásico con la mutación BRAF que recibió trametinib (2 mg/día) y dabrafenib (200 mg/día) después de usar interferón sin beneficio. Después de iniciar esta terapia la paciente notó una incapacidad de abducir el ojo izquierdo. Ocho días después de iniciar el tratamiento, tuvo falta de apetito, vómitos, diarrea, vértigo y fiebre de 40°C. Dos días después notó pérdida de su agudeza visual, requiriendo asistencia para efectuar sus actividades de vida diaria. Dos días después apareció coluria, en ausencia de mialgias o debilidad muscular, pero acompañadas de fatiga. Ella no pudo comer o tomar líquidos por cuatro días antes de ingresar al hospital. La paciente sospechó que estaba experimentando efectos secundarios de los medicamentos y los suspendió dos días antes del ingreso, experimentando una casi completa remisión de sus síntomas, con excepción de la debilidad de musculatura ocular y déficit visual.

Anticonvulsant hypersensitivity syndrome: clinic case and literature review.

INTRODUCTION: The anticonvulsant hypersensitivity syndrome is a rare adverse reaction in which the skin, lymph nodes and internal organs are affected. It is usually caused by classic anticonvulsants such as phenytoin, carbamazepine or phenobarbital. CASE REPORT: Here we present the case of a 25-year-old woman from Córdoba, Argentina, who suffered a severe reaction to oxcarbazepine with a rash, lymphadenopathy, hepatitis and an unusual analytic. Clinical abnormalities were reversed after oxcarbazepine was terminated and treatment with diphenhydramine and dexamethasone was initiated. DISCUSSION: DRESS syndrome is a hypersensitivity reaction that takes weeks to manifest, and is characterized by rash, leukocytosis with eosinophilia, adenopathies, liver involvement, and reactivation of the herpes virus 6, being more frequent in carbamazepine or phenytoin, and in rare cases to oxcarbazepine. CONCLUSIONS: In general, this strong medicine is not taken into account as a cause of hypersensitivity, reports suggest that it could be related to cases similar to this one, and studies that are more targeted are required, due to the morbidity and mortality of the syndrome.

Introducción: El síndrome de hipersensibilidad a los anticonvulsivantes es una reacción adversa rara en la que se ven afectados la piel, los ganglios linfáticos y los órganos internos. Generalmente es causada por anticonvulsivos clásicos como fenitoína, carbamazepina o fenobarbital. Caso clínico: Aquí presentamos el caso de una mujer de 25 años de Córdoba, Argentina, que sufrió una reacción severa a la oxcarbazepina con una erupción cutánea, linfadenopatías, hepatitis y un analítico inusual. Las anormalidades clínicas se revirtieron después de que se terminara la oxcarbazepina y se inició el tratamiento con difenhidramina y dexametasona. Discusión: El síndrome DRESS es una reacción de hipersensibilidad que tarda semanas en manifestarse, y se caracteriza por exantema, leucocitosis con eosinofilia, adenopatías, afectación hepática, y reactivación del virus herpes 6, siendo más frecuente ante carbamazepina o fenitoína, y en raros casos a oxcarbazepina. Conclusiones: Por lo general, este medicamento fuerte no se toma en cuenta como causa de hipersensibilidad, los informes sugieren que podría estar relacionado con casos similares a este, y se requieren estudios que sean más dirigidos, debido a la morbimortalidad del síndrome.

Caso Clínico: Citopénia Autoinmune como complicación inmunológica de Trasplante Alogénico de Donante no emparentado, en paciente pediátrico con Anemia Drepanocítica / Clinical Case: Autoimmune Cytopenia as an immunological complication of Allogeneic Unrelated Donor Transplantation, in a pediatric patient with Sickle Cell Anemia

Introducción: La enfermedad de células falciformes es una condición heredada en la quese produce una hemoglobina anómala que desfavorece a la oxigenación tisular, crisis vaso-oclusivas y reacciones hemolíticas. Los pacientes con esta enfermedad presentan una activación anómala de la vía del complemento llevándolos al aumento en frecuencia de infecciones y enfermedades autoinmunes. Presentamos un caso de asociación de una enfermedad autoinmune en un paciente con enfermedad de células falciforme. Caso clínico: Niño de 10 años con Anemia drepanocítica (2009) con esplenectomía y crisis veno-oclusivas recurrentes, fue sometido a trasplante Alogénicoen abril del 2019fuera de la institución con donante isogrupo O+ no emparentado (10/10). Tratado con: Fludarabina ­Busulfan, Timoglobulina+ y Metotexate. Desarrolló Bicitopenia autoinmune y síndrome febril al día +165 post TPH. Glóbulos blancos: 360 uL, neutrófilos: 14 %, hemoglobina: 7.90 g/dL, plaquetas: 25000 uL, ferritina: 4695 ng/ml, IgG total: 9.88 gr/l, LDH: 190 UI/l. Proteína C reactiva: 2.79 mg/dL, Procalcitonina 0.13 ng/mL. Evolución: posterior a descartar infección viral, se completó un tratamiento antibiótico de amplio espectro y se realizó la suspensión del tratamiento inmunosupresor por sospecha de toxicidad, sin respuesta. Se realizó un estudio medular por citometría de flujo determinando una disminución de la línea linfoide B, y se concluye Citopenia Autoinmune como complicación inmunológica del trasplante. Desenlace: recibióterapia transfusional (plaquetoféresis + glóbulos rojos concentrados). Se utilizó metilprednisolona IV por 3 días y prednisona 30 mg por 14 días con reducción posterior gradual para inicio de Rituximab y ciclosporina. Se completó el tratamiento con Imnunoglobulina 6g IV por 5 días. Al alta glóbulos blancos: 5080 uL, neutrófilos: 67%, hemoglobina: 9.20 g/dL, plaquetas: 20000 uL, después de 18 días de ingreso hospitalario. Conclusión: Los resultados con el tratamiento en este caso sugieren que puede serrazonable considerar las citopeniasautoinmunes como una manifestación hematológica diagnóstica de la EICH crónica. Alternativamente, es posible que el tratamiento de citopenia inmune con esteroides, Rituximab y otros inmunosupresores

Introduction: Sickle cell disease is an inherited condition in which an abnormal hemoglobin is produced that impairs tissue oxygenation, vaso-occlusive crises and hemolytic reactions. Patients with this disease present an abnormal activation of the complement pathway, leading to an increase in the frequency of infections and autoimmune diseases. We present a case of association of an autoimmune disease in a patient with sickle cell disease. Clinical case:10-year-old boy with sickle cell anemia (2009) with splenectomy and recurrent veno-occlusive crisis, underwent Allogeneic transplantation in April 2019 outside the institution with an unrelated isogroup O + donor (10/10). Treated with: Fludarabine -Busulfan, Thymoglobulin + and Metotexate. He developed autoimmune bicytopenia and febrile syndrome at +165 day post HSCT. White blood cells: 360 uL, neutrophils: 14%, hemoglobin: 7.90 g / dL, platelets: 25,000 uL, ferritin: 4695 ng / ml, total IgG: 9.88 gr / l, LDH: 190 IU/l. C-reactive protein: 2.79 mg/dL, procalcitonin 0.13 ng / mL. Evolution:after ruling out viral infection, the patient completed a broad-spectrum antibiotic treatment and underwent suspension of immunosuppressive treatment due to suspected toxicity, with no response. A medullary study by flow cytometry was performed, determining a decrease in the B lymphoid line, and autoimmune cytopenia was concluded as an immunologicalcomplication of the transplant. Outcome:The patient received transfusion therapy (plateletpheresis + concentrated red blood cells). He also received IV methylprednisolone for 3 days and 30 mg prednisone for 14 days with gradual subsequent reduction to start Rituximab and cyclosporine. The treatment with Immunoglobulin 6g IV for 5 days was completed. At discharge, white blood cells: 5080 uL, neutrophils: 67%, hemoglobin: 9.20 g / dL, platelets: 20,000 uL, after 18 days of hospital admission. Conclusion:The results with treatment in this case suggest that it may be reasonable to consider autoimmune cytopenias asa diagnostic hematological manifestation of chronic GVHD. Alternatively, it is possible to treat immune cytopenia with steroids, rituximab, and other immunosuppressants

Manifestaciones hematologicas en pacientes adultos con lupus eritematoso sistémico / Hematological manifestations in adult patients with systemic lupus erythematosus

Introducción: el lupus erimatoso sistémico (LES) puede afectar las tres series celulares de la sangre. Objetivo: describir las alteracoines hematológicas y los marcadores de actividad en pacientes adultos con LES. Metodología: estudio observacional descriptivo realizado en pacientes con LES en el Hospital Nacional en 2017-2018. Se excluyeron a los pacientes con inmunosupresores (ciclofosfamida, rituzimab), pacientes con LES medicamentoso, pacientes con síndrome de superposición, pacientes con otras enfermedades autoinmunes. Resultados: se incluyeron 88 pacientes, con edad media 27±15 años. Hubo predominio de mujeres (89%). Se detectó anemia en 55%, leucopenia en 13%, linfopenia en 32%, plaquetopenia en 11%. Los valores de ANA estaban elevados en 92% y anti DNA en 22%. Conclusión: la afectación hematológica más frecuente en pacientes adultos con LES fue la anemia, seguida por la leucopenia y la plaquetopenia.

Introduction: systemic lupus erythematosus (SLE) can affect the three celular series of the blood. Objective: to describe hematological alterations and activity markers in adult patients with SLE. Methodology: descriptive observational study performed in patients with SLE of the National Hospital in 2017-2018. Were excluded patients with immunosuppressants (cyclophosphamide, rituzimab), patients with drugs induled SLE, patients with overlap syndrome, patients with other autoimmune diseases. Results: 88 patients were included, with an average age of 27 ± 15 years. There was a predominance of women (89%). Anemia was detected in 55%, leukopenia in 13%, lymphopenia in 32%, thrombocytopenia in 11%. ANA values were high in 92% and anti DNA in 22%. Conclusion: the most frequent haematological compromise in adult patients with SLE was anemia, followed by leukopenia and thrombocytopenia.

Respuesta a Factores Estimulantes de Colonias de Granulocitos en eventos de Neutropenia Febril en pacientes Oncológicos del Instituto del Cáncer Solca-Cuenca / Response to Stimulating Factors of Granulocyte Colonies in Febrile Neutropenia Events in Oncological Patients of the Cancer Institute Solca-Cuenca

Introducción: La Neutropenia Febril es una complicación potencialmente fatal del tratamiento del cáncer, relacionada con mayor morbilidad, mortalidad, disminución de dosis o retardo en los ciclos de quimioterapia, y resultados finales pobres. Estudios anteriores han demostrado el beneficio de Factor Estimulante de Colonias de Granulocitos en la reducción de tiempo de hospitalización, antibióticos intravenosos, fiebre y recuperación del conteo absoluto de neutrófilos. Se decide realizar el presente reporte ya que no existen datos respecto al manejo y respuesta al tratamiento en nuestro medio. Métodos: El presente estudio descriptivo, retrospectivo, fue realizado en el Instituto del Cáncer SOLCA ­ Cuenca. Se revisaron las historias clínicas del período 2010 ­ 2011. Las variables analizadas fueron: número de días de hospitalización, fiebre, uso de antibióticos intravenosos, y días de recuperación de neutropenia a >500/mm3 y >1000/mm3. Resultados: La estancia hospitalaria tuvo una mediana de 6 días, los días de terapia antibiótica intravenosa fueron iguales a los días de hospitalización. 79 eventos se recuperaron a un conteo absoluto de neutrófilos >500/mm3, en una mediana de 4 días; 72 eventos se recuperaron a >1000 /mm3 en una mediana de 4 días. La mayoría de los eventos se volvieron afebriles en una mediana de 1 día. Conclusión: Los resultados de las variables estancia hospitalaria, uso de antibióticos intravenosos y la duración de la fiebre fueron similares a los ya descritos en estudios anteriores, la recuperación del conteo absoluto de neutrófilos, fue más tardía, mostrando diferencias importantes con la bibliografía.

Introduction: Febrile Neutropenia is a potentially fatal complication of cancer treatment, related to higher morbidity, mortality, dose reduction or retard in chemotherapy cycles, and poor final outcomes. Previous studies have demonstrated the benefit of G-CSF (Granulocyte ­ Colony Stimulating Factors) in reduction of hospital stay, the use of intravenous antibiotics, fever and absolute neutrophil count (ANC) recovery. There is no data about the management and treatment response in our population. Methods: This is a retrospective descriptive study, developed in SOLCA ­ Cuenca Cancer Institute. 83 febrile neutropenia events met the inclusion and exclusion criteria, medical records from years 2010 to 2011 were reviewed. The analyzed variables were: days of hospital stay, fever, intravenous antibiotics use, and neutropenia recovery to a level >500/mm3 and >1000/mm3. Results: The median of hospital stay was 6 days, the duration of IV antibiotic therapy was the same as the days of hospital stay. 79 events recovered to an ANC >500/mm3, with a median of 4 days; 72 events recovered to >1000 /mm3 with a median of 4 days. The majority of events became afebrile with a median of 1 day. Conclusion: The results in the variables hospital stay, use of intravenous antibiotics and fever duration, were similar to those described in previous studies. The ANC recovery was delayed, showing important differences with cited references.