Efficacy and safety of non-vitamin K antagonist versus vitamin K antagonist oral anticoagulants in the prevention and treatment of thrombotic disease in active cancer patients: a systematic review and meta-analysis of randomized controlled trials / 中华心血管病杂志

Object We aimed to compare the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonist (VKA) in the prevention and treatment of thrombotic diseases in patients with active cancer. Methods: To find randomized controlled trials (RCT) in which NOACs were compared VKAs in active cancer, we searched the electronic databases (PubMed, Web of Science and Clinical Trials) up to May 2019 and and languages restricted to Chinese and English. According to the screening strategy, two researchers independently screened and extracted literature, evaluated the quality of literature, the suitability of collected cross study data for analysis, and tested the heterogeneity. The relative risk (RR) and 95% confidence interval (95%CI) of major bleeding, clinically related non-major bleeding, VTE, stroke and all-cause mortality in active cancer patients with VTE, active cancer patients with non-valvular atrial fibrillation (NVAF) was calculated and the results were compared between NOAC with VKA. Results: A total of 9 RCTs were included, including 5 cancers with VTE (5/9) and 4 cancers with NVAF (4/9). A total of 5 867 patients were included. After excluding 1 818 (30.99%) patients with cancer history, 4 049 (68.86%) patients with active cancer were statistically analyzed. Among them, 2 278 (56.26%) received NOAC treatment, 1 771 patients (43.74%) received VKA treatment. The quality of the included documents was high (all scores were>5 points), and the data of each included document could be summarized and analyzed (P>0.05). The heterogeneity of main outcome events was very low (I2 = 0). In VTE patients with active cancer, NOACs were more effective in reducing recurrence of VTE （RR=0.55, 95%CI 0.36 -0.84; P = 0.005) and clinically related non-major bleeding (RR=0.77, 95%CI 0.60 -0.98; P = 0.03) than VKAs. In NVAF patients with active cancer, efficacy of NOACs and VKAs was similar in terms of reducing VTE, stroke, clinically related non-major bleeding, major bleeding and all-cause mortality events (P>0.05). Conclusions: For patients with active cancer accompanied by VTE, NOAC may has more advantages in efficacy and safety compared to VKA in the prevention and treatment of thrombotic diseases.

Intoxicación con rodenticidas anticoagulantes: serie de casos y revisión de literatura / Intoxication with anticoagulant rodenticides: Case series and review of the literature

Introducción. Los superwarfarinicos (SWF) son una de las herramientas utilizadas por el ser humano para el control de roedores y a la vez son tóxicos para el hombre y pueden conducir a la muerte sin los debidos cuidados en su uso.Casos clinicos. Tres pacientes masculinos, que consultaron por sangrados (gingivorragia, epistaxis, hematuria, hemartrosis y hematomas cutaneos) asociados a alteraciones del coagulograma (Tiempo de protrombina (TP) y tiempo de tromboplastina parcial (KPTT) prolongados). Todos tuvieron exposición a superwarfarinicos. Nuestro servicio no dispone del análisis de SWF en suero. Se administró vitamina K1 en los tres pacientes y plasma fresco congelado (PFC) en uno solo (sangrado mayor: hematuria). El seguimiento se realizó mediante controles seriados de coagulograma y su evolución fue favorable. Discusión. En todos los casos, el diagnóstico de intoxicación por SWF fue clínico, basado en caracteristicas clínicas de pacientes y alteraciones en sus parámetros de coagulación, y debido a imposibilidad de derivación de análisis a otro laboratorio. Se realizo tratamiento especifico (vitamina K1 y PFC) segun recomendación de expertos, ya que no hay hasta la fecha, estudios clinicos que evaluen las diferentes opciones terapéuticas. Conclusión. La intoxicación por SWF aunque no es frecuente, debe sospecharse en casos de paciente con coagulopatia sin otras causas que puedan justificarlo. El manejo del cuadro tóxico es la reposición de vitamina k y de plasma fresco congelado, en casos donde se necesite una rápida corrección de la alteración hemostática, como los sangrados mayores. Es imprescindible la oportuna consulta con médicos hematólogos y/o la consulta con un centro regional de control de intoxicaciones para todas las exposiciones sospechosas por SWF.

Introduction. Superwarfarinics (SWF) are one of the tools used by humans for rodent control. They are toxic to humans and can lead to death without due care in its use. Clinical cases. Three male patients, who consulted due to bleeding (gingivorragia, epistaxis, hematuria, hamartrosis and skin hematomas) associated with coagulogram alterations (prolonged protombine time (PT) and partial thromboplastin time (KPTT)). All them exposure to superwarfarinics. SWF serum analysis was not available in our hospital. Vitamin K1 was administered in all three patients and fresh frozen plasma (PFC) in only one (major bleeding: hematuria). The followup was performed by serial coagulogram controls and the evolution was. Discussion. In all cases, the diagnosis of SWF intoxication was clinical, based on clinical characteristics of patients and alterations in their coagulation parameters, due to the impossibility of deriving the analysis of SWF in serum to another laboratory. Specific treatment was carried out (vitamin k and PFC) according to experts' recommendation, since there are no clinical studies to evaluate the different therapeutic options to date. Conclusion. SWF poisoning, although not frequent, should be suspected in patients with coagulopathy without other causes that may justify it. The management of toxic symptoms is the administration of vitamin K1 and fresh frozen plasma, in cases where a rapid correction of the haemostatic alteration is required, such as major bleedings. It is essential to consult with hematologists and / or consult a regional poison control center for all suspicious exposures by superwarfarins.

Esclerose lateral amiotrófica: novas possibilidades terapêuticas em um arcabouço fisiopatológico ainda em construção / Amyotrophic lateral sclerosis: new therapeutic possibilities in a pathophysiological framework still under construction

Introdução: A Esclerose Lateral Amiotrófica (ELA) é definida como uma doença neurológica progressiva e inexorável, com cerca de 80% dos casos de etiologia desconhecida. Novos medicamentos têm emergido no tratamento de doenças neurodegenerativas, inclusive na ELA, redesenhando o modelo fisiopatológico. Dentre eles, destacam-se o uso da: Edaravone, Vitamina K2, Serina, Metilcobalamina, Pirroloquinolina quinona (PQQ), Ubiquinol e Glutationa. Especificamente na ELA, alguns já foram validados em estudos randomizados-controlados. Metodologia: Atualização da literatura (PUBMED, Medline) sobre a utilização desses fármacos em doenças neurológicas degenerativas, com enfoque para a Doença do Neurônio Motor (DNM-ELA), nos idiomas Português, Inglês, Espanhol e Francês, compreendidos entre os anos de (2010-2017). Discussão: A associação desses medicamentos tem mostrado resultados positivos em inúmeras doenças neurológicas. Alguns, como, por exemplo, a Metilcobalamina e o Edaravone,exerceriam mecanismos de ação capazes de interferir no processo de depleção dos neurônios motores da ponta anterior e do feixe piramidal em pacientes com ELA. Conclusão: Seria precipitado concluir que o uso associado desses fármacos poderia modificar ou mesmo restaurar os danos às unidades motoras; entretanto, faz-se necessário destacar seus mecanismos de ação e potencial capacidade de intervir na evolução da doença, principalmente, a partir de estudos em modelos fisiopatológico que culminam na degeneração dos neurônios motores.(AU)

Introduction: Amyotrophic Lateral Sclerosis (ALS) is defined as a progressive and inexorable neurological disease, with about 80% of cases of unknown etiology. New drugs have emerged in the treatment of neurodegenerative diseases, including ALS, redesigning the pathophysiological model. Among them, the use of: Edaravone, Vitamin K2, Serine, Methylcobalamin, Pyrroloquinoline quinone (PQQ), Ubiquinol and Glutathione are noteworthy. Specifically in ALS, some have been validated in randomized controlled trials. Methodology: Update of the literature (PUBMED, Medline) on the use of these drugs in degenerative neurological diseases, with a focus on Motor Neuron Disease (DNM-ELA) in the Portuguese, English, Spanish and French languages, of (2010-2017). Discussion: The association of these drugs has shown positive results in neurological diseases. Some, such as Methylcobalamin and Edaravone, would exert mechanisms of action capable of interfering in the process of depletion of the motor neurons of the anterior horn and pyramidal tracts in patients with ALS. Conclusion: It would be precipitate to conclude that the associated use of these drugs could modify or even restore damage to motor units; however, it is necessary to highlight its mechanisms of action and potential ability to intervene in the evolution of the disease, mainly from studies in pathophysiological models that culminate in the degeneration of motor neurons (AU)

Anticoagulantes não antagonistas da vitamina K na prevenção do acidente vascular cerebral / Non-vitamin K antagonist anticoagulants in the prevention of stroke

O acidente vascular cerebral isquêmico (AVCi) causado por fibrilação atrial (FA) é comum e mais grave que os de outra etiologia. Devido à eficácia e segurança maiores ou similares dos anticoagulantes orais diretos (DOAC) comparados à varfarina e à comodidade de uso, esses fármacos são considerados o tratamento de escolha na prevenção do AVCi por FA. Pacientes com FA e AVCi agudo apresentam alto risco de recorrência e devem ser submetidos à anticoagulação precoce, seguindo-se a "regra 1, 3, 6, 12 dias". Nos casos de acidente vascular cerebral hemorrágico (AVCh) durante o uso de (DOAC), pode-se recomendar o concentrado de complexo protrombínico, porém não há evidência que apoie essa conduta. O advento dos agentes reversores traz a oportunidade de ampliar o uso dos DOAC, porque proporcionam maior controle nas situações de urgência, como o AVC. Por serem mais fáceis de usar e apresentarem menor interação medicamentosa, os DOAC assumem um importante papel nos pacientes com declínio cognitivo. Pacientes com FA não devem ser excluídos do uso de anticoagulantes somente por apresentarem alto risco de quedas. Para pacientes com indicação de anticoagulação, os benefícios geralmente suplantam os riscos

Atrial fibrillation (AF)-related ischemic stroke (IS) is common and more severe than stroke due to other causes. Due to the greater or similar efficacy and safety to direct oral anticoagulants (DOAC) compared to warfarin, and their ease of use, these drugs are considered the treatment of choice for the prevention of AF-related stroke. Patients with AF and acute IS present a high risk of recurrent stroke and should be submitted to early anticoagulation, following the "1-3-6-12 day rule". In cases of DOACs-related intracerebral hemorrhage (ICH), prothrombin complex concentrate (PCC) can be recommended for use, but there is no evidence to support this conduct. The advent of reversal agents brings the opportunity to increase the use of DOACs, because they provide better control in emergency situations, such as stroke. Because they are easy to use and present less drug interactions, DOACs play an important role in patients with cognitive decline. Patients with AF should not be excluded from the use of oral anticoagulants solely because they present high risk of falls. For patients with a valid indication for anticoagulation, the benefits generally outweigh the risks

Hipobetalipoproteinemia primária: relato de caso / Primary Hypobetalipoproteinemia: a case report

Descrevemos o caso de uma paciente de 19 anos diagnosticada com hipobetalipoproteinemia primária. A paciente apresentava sintomas compatíveis com a doença como diarreia desde o primeiro mês de vida, défice de crescimento e retinopatia. A biópsia duodenal evidenciou presença de vacúolos lipídicos intraepiteliais, os quais foram altamente sugestivos para o diagnóstico. Os exames complementares evidenciaram disfunção hepática, baixos níveis séricos de triglicerídeos, e de colesterol total e frações. Após a dosagem de apolipoproteína B abaixo dos valores da normalidade, aliada a clínica e exames complementares, o diagnóstico foi realizado. A relativa escassez de dados na literatura em nosso meio, atrelada à raridade da doença, ilustra a relevância deste relato de caso, somado à importância do diagnóstico precoce

The case of a 19-year-old female patient who was diagnosed with Primary Hypobetalipoproteinemia (HBL) is described.The patient presented symptoms that were consistent with the disease, such as diarrhea from the very first month of life, growth failure and retinopathy. The duodenal biopsy showed the presence of intraepithelial lipid vacuoles that were highly suggestive of the diagnosis. Further tests showed liver dysfunction, low serum levels of triglycerides and total cholesterol and fractions. After the dosage of Apolipoprotein B below normal values, and clinical exam along with laboratory tests, the diagnosis was made. The lack of data in the literature and the rarity of the disease illustrate the importance of this case report,and of an early diagnosis.

Estudo transversal das estratégias de tratamento clínico na fibrilação atrial / Cross-sectional study of treatment strategies on atrial fibrillation / Estudio transversal de las estrategias de tratamiento clínico en la fibrilación atrial

FUNDAMENTO: A despeito de elevada prevalência e importância clínica da Fibrilação Atrial (FA), não existem até o momento publicações brasileiras informando o perfil clínico e a estratégia de tratamento (controle de ritmo vs. controle de frequência cardíaca) mais utilizada nesse universo de pacientes. OBJETIVO: Avaliar a estratégia de tratamento mais empregada na FA em ambulatório especializado no manejo dessa doença. Secundariamente, procurou-se descrever o perfil clínico dessa população. MÉTODOS: Estudo transversal que avaliou sequencialmente, em 167 portadores de FA, a estratégia de tratamento mais empregada, bem como o perfil clínico desses pacientes. Utilizou-se questionário padronizado para coleta de dados. A análise estatística foi realizada por meio do software SPSS® versão 13.0. RESULTADOS: Nessa população de alto risco para eventos tromboembólicos (61% com score CHADS2 > 2), em que 54% dos indivíduos apresentavam fibrilação atrial paroxística ou persistente, 96,6% utilizavam antagonistas da vitamina K ou AAS, e 76,6% faziam uso de betabloqueador (81,2% frequência x 58,8% ritmo, p < 0,05); a estratégia de controle de frequência foi a mais empregada (79,5% x 20,5%, p < 0,001). Houve uma tendência estatística a maior agrupamento de pacientes com disfunção ventricular (15,2% x 2,9%; p = 0,06), CHADS2 > 2 (60,5% x 39,5%; p = 0,07) e valvopatias (25,8% x 11,8%; p = 0,08) no segmento de controle da frequência. CONCLUSÃO: Nessa população de alto risco para eventos tromboembólicos, a estratégia de controle de frequência cardíaca foi a mais empregada.

BACKGROUND: Despite the high prevalence and clinical importance of atrial fibrillation (AF), there is no Brazilian study about the clinical profile of patients with AF and the most used treatment strategy (heart rhythm control vs. heart rate control) for them. OBJECTIVE: To assess the most used treatment strategy for AF in an outpatient clinic specialized in the management of that disease. In addition, the clinical profile of the population studied was provided. METHODS: Cross-sectional study assessing sequentially, in 167 patients with AF, the most used treatment strategy, as well as their clinical profile. A standardized form was used for data collection. The statistical analysis was performed by using the SPSS® software, version 13.0. RESULTS: In that population at high risk for thromboembolic events (61% had CHADS2 > 2), 54% of the patients had paroxysmal or persistent AF, 96.6% used vitamin K antagonists or acetylsalicylic acid, and 76.6% used beta-blocker (heart rate, 81.2% x heart rhythm, 58.8%; p < 0.05). Heart rate control was the most used treatment strategy (79.5% x 20.5%; p < 0.001). A statistical tendency towards more patients with ventricular dysfunction (15.2% x 2.9%; p = 0.06), CHADS2 > 2 (60.5% x 39.5%; p = 0.07) and heart valve diseases (25.8% x 11.8%; p = 0.08) was observed in the heart rate control group. CONCLUSION: In that population at high risk for thromboembolic events, the heart rate control strategy was the most used.

FUNDAMENTO: A despecho de la elevada prevalencia y importancia clínica de la Fibrilación Atrial (FA), no existen hasta el momento publicaciones brasileñas informando el perfil clínico y la estrategia de tratamiento (control de ritmo vs. control de frecuencia cardíaca) más utilizada en ese universo de pacientes. OBJETIVO: Evaluar la estrategia de tratamiento más empleada en la FA en ambulatorio especializado en el manejo de esa enfermedad. Secundariamente, se buscó describir el perfil clínico de esa población. MÉTODOS: Estudio transversal que evaluó secuencialmente, en 167 portadores de FA, la estrategia de tratamiento más empleada, así como el perfil clínico de esos pacientes. Se utilizó cuestionario estandarizado para recolección de datos. El análisis estadístico fue realizado por medio del software SPSS® versión 13.0. RESULTADOS: En esa población de alto riesgo para eventos tromboembólicos (61% con escore CHADS2 > 2), en que 54% de los individuos presentaban fibrilación atrial paroxística o persistente, 96,6% utilizaban antagonistas de la vitamina K o AAS, y 76,6% hacían uso de betabloqueante (81,2% frecuencia x 58,8% ritmo, p < 0,05); la estrategia de control de frecuencia fue la más empleada (79,5% x 20,5%, p < 0,001). Hubo una tendencia estadística la mayor agrupamiento de pacientes con disfunción ventricular (15,2% x 2,9%; p = 0,06), CHADS2 > 2 (60,5% x 39,5%; p = 0,07) y valvulopatías (25,8% x 11,8%; p = 0,08) en el segmento de control de la frecuencia. CONCLUSION: En esa población de alto riesgo para eventos tromboembólicos, la estrategia de control de frecuencia cardíaca fue la más empleada.

Parvovirus B19 nonimmune hydrops in a neonate.

Parvovirus B19 is responsible for approximately 10% of all cases of nonimmune hydrops. An unusual case of perinatally acquired parvovirus infection in a neonate is reported who presented with nonimmune hydrops fetalis at D15 of life.

Reversão da anticoagulação oral em situações de risco / Oral anticoagulation reversion in risk situations

A melhora do conhecimento dos mecanismos de ação dos anticoagulantes, de sua eficácia e de sua segurança tem levado ao aumento progressivo do número de pacientes anticoagulados. A anticoagulação pode ser indicada tanto para prevenção de eventos tromboembólicos nos portadores de fibrilação atrial ou prótese cardíaca mecânica como para tratamento após evento trombótico agudo. Com o evidente aumento do número de pacientes anticoagulados, a ocorrência de eventuais necessidades curúrgicas nesses pacientes tem sido cada vez mais frequente. Diante desas situações de maior risco, será fundamental o preparo do paciente. A conduta deverá ser individualizada e levará em considerações dois aspectos fundamentais: risco trombótico do paciente e risco hemorrágico do procedimento. OS pacientes que serão submetidos a procedimento de alto risco hemorrágico deverão ter sua anticoagulação revertida, porém a reversão da anticoagulação poderá expor o paciente a alto risco trombótico. Acompanhamento multiprofissional com a indicação de medicamentos que atuam de forma...

A study of Vitamin K status in children on prolonged antibiotic therapy.

Vitamin K deficiency is known to cause coagulopathy and bleeding in patients on prolonged antibiotic therapy. This study was conducted to evaluate the status of vitamin K deficiency in hospitalized children on prolonged antibiotic therapy and its role in reversing the coagulopathy. A prospective non-randomized study was conducted on children on antibiotic therapy at a tertiary care hospital. Children in the 1 month-1 year age group developed significant coagulopathy as compared to other age groups. Coagulation abnormalities were also seen to be more in children with greater grades of malnutrition, on a more prolonged course of antibiotics and in children who were critically ill in intensive care. Hypoprothrombinemia previously reported to be due to B-lactam antibiotics containing the N-Methyl Thio Tetrazole (NMTT) group also resulted from antibiotics without this side chain. Inhibition of intestinal microorganisms by antibiotics was thought to be a likely explanation of this phenomenon. We suggest Vitamin K prophylaxis in severely ill patients, on extended periods of antibiotics and inadequate diet to prevent morbidity and mortality.

Rosacea: tratamiento con vitamina K topica / Rosacea: vitamin K therapy

La rosácea es una dermopatía que afecta selectivamente la cara, caracterizada por la aparición sucesiva o simultánea de eritema, telangiectasias, pápulas y pústulas, siendo el eritema su sustrato obligado y las dilaciones vasculares una etapa de comienzo. Se realiza un ensayo terapéutico con vitamina K en forma de máscara y en crema para uso diario con una respuesta eficaz en la disminución del eritema

Acidosis tubular renal / Renal tubular acidosis

Los transtornos de acidificación renal se manifiestan por síntomas y signos poco específicos, por lo que el pediatra debe sospechar el diagnóstico frente a un niño con dificultad en el progreso ponderal, anorexia, poliuria y que en los exámenes presenta acidosis metabólica hiperclómerica. Con estos antecedentes es importante la derivación oportuna al nefrólogo para la determinación del tipo de acidosis tubular renal y el tratamiento adecuado que repercutirá en el pronóstico vital del niño

Anastomosis de colon en niños / Colon of anastomosis in children

En 53 pacientes intervenidos entre los años 1979 y 1997, se practicaron un total de 55 anastomosis de colon. En su gran mayoría se utilizó la técnica descrita por Goligher en su libro de texto, complementada con estudios radiológicos para asegurar la permeabilidad del colon, preparación preoperatoria del colon y utilización de suturas no reabsorbidas. No se presentaron complicaciones inherentes a la técnica

Changes of serum lipids in vitamin K3 (menadione) treated rats / Modificaciones de los lipidos sericos en ratas tratadas con vitamina K3 (menadiona)

The effect of high dosers of vitamin K3 (10 to 50 mg/kg/day of menadione, administered intramuscularly) on the serum content of total lipids, cholesterol, phospholipids and triglycerides in male Wistar rats was evaluated. This experimental group was compared with another group that received intramuscular injections of 10 to 50 mg/kg/day of sodium bisulphite. Hypervitaminosis K3 was diagnosed by jaundice (due mainly to unconjugated bilirrubin) and by anemia which was particulary evident at doses of 40 and 50 mg/kg/day of menadione. These doses of menadione increased serum content of total lipids, phospholipids, and triglycerides but decreased cholesterol. The results show that overdoses of vitamin K3 alter lipid metabolism. The influence o participation of liver damage, fastening, as well as various endocrine and hematological changes are considered responsible for the alterations in serum lipids