Superior ophthalmic vein and cavernous sinus thrombosis associated with COVID-19: a case report / Trombose de veia oftálmica superior e seio cavernoso associada à COVID-19: relato de caso

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.

RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.

Manejo del paciente anticoagulado en una cirugía dental / Management of the anticoagulated patient in dental surgery / Gerenciamento do paciente anticoagulado em cirurgia odontológica

Introducción: una adecuada hemostasia es crucial para el éxito del tratamiento odontológico invasivo, ya que los problemas de sangrado pueden dar lugar a complicaciones asociadas a una importante morbimortalidad. El tratamiento odontológico de pacientes que tienden a un mayor riesgo de sangrado debido al uso de fármacos anticoagulantes plantea un desafío en la práctica diaria de los profesionales de la odontología. El conocimiento adecuado de los mecanismos subyacentes a la hemostasia y el manejo optimizado de estos pacientes son, por lo tanto, cuestiones muy importantes. Se realiza un estudio de los fármacos anticoagulantes actualmente disponibles en el mercado, evaluando los riesgos y beneficios de suspender dicho fármaco previo a un tratamiento odontológico invasivo. Además, se hace una revisión de los protocolos de manejo actuales que se utilizan en estos pacientes. Material y métodos: se realizó una búsqueda bibliográfica en las bases de datos Epistemonikos y Medline/PubMed; en el portal Timbó y en la biblioteca virtual Scielo. Abarcando todos los estudios publicados en los últimos 15 años en inglés y español. Se encontraron 30 artículos, se seleccionaron 15 en primera instancia para finalizar con 11 artículos. En dicha selección el filtro fue que los demás artículos se referían a otros anticoagulantes que no eran parte de este trabajo. Resultados: se han desarrollado múltiples protocolos de manejo, aunque en todos los casos se requiere una historia clínica completa, junto con pruebas hemostáticas complementarias para minimizar los riesgos derivados del tratamiento odontológico. Discusión: muchos autores consideran que la medicación de los pacientes indicada para el tratamiento de una enfermedad de base no debe ser alterada o suspendida a menos que así lo indique el médico prescriptor. Se ha demostrado que las medidas hemostáticas locales son suficientes para controlar los posibles problemas de sangrado derivados del tratamiento dental.

Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can lead to complications associated with significant morbidity and mortality. The dental treatment of patients who are prone to an increased risk of bleeding due to the use of anticoagulant drugs poses a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis and optimized management of these patients are therefore very important issues. A review is made of the anticoagulant drugs currently available on the market, evaluating the risks and benefits of suspending such a drug prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and methods: A bibliographic search was carried out in the Epistemonikos and Medline/PubMed databases; in the Timbo portal and in the Scielo virtual library. All the studies published in the last 15 years in English and Spanish were included. Thirty articles were found, 15 were selected in the first instance to end up with 11 articles. In this selection, the filter was that the other articles referred to other anticoagulants that were not part of this work. Results: multiple management protocols have been developed, although in all cases a complete clinical history is required, together with complementary hemostatic tests to minimize the risks derived from dental treatment. Discussion: many authors consider that the patient's medication indicated for the treatment of an underlying disease should not be altered or suspended unless so indicated by the prescribing physician. It has been shown that local hemostatic measures are sufficient to control possible bleeding problems derived from dental treatment.

Introdução: A hemostasia adequada é crucial para o sucesso do tratamento dentário invasivo, pois problemas de sangramento podem levar a complicações associadas a uma morbidade e mortalidade significativas. O tratamento odontológico de pacientes que são propensos a um risco maior de sangramento devido ao uso de drogas anticoagulantes representa um desafio na prática diária dos profissionais da odontologia. O conhecimento adequado dos mecanismos subjacentes à hemostasia e o gerenciamento otimizado desses pacientes são, portanto, questões muito importantes. É realizada uma revisão dos anticoagulantes atualmente disponíveis no mercado, avaliando os riscos e benefícios de descontinuar tal medicamento antes do tratamento dentário invasivo. Além disso, é feita uma revisão dos protocolos de gerenciamento atuais usados nesses pacientes. Material e métodos: Foi realizada uma pesquisa bibliográfica nas bases de dados Epistemonikos e Medline/PubMed; no portal Timbo e na biblioteca virtual Scielo. Todos os estudos publicados nos últimos 15 anos, em inglês e espanhol, foram incluídos. Trinta artigos foram encontrados, 15 foram selecionados em primeira instância para acabar com 11 artigos. Nesta seleção, o filtro foi que os outros artigos se referiam a outros anticoagulantes que não faziam parte deste trabalho. Resultados: foram desenvolvidos múltiplos protocolos de gerenciamento, embora em todos os casos seja necessário um histórico clínico completo, juntamente com testes hemostáticos complementares para minimizar os riscos derivados do tratamento odontológico. Discussão: muitos autores consideram que a medicação os pacientes indicada para o tratamento de uma doença subjacente não deve ser alterada ou descontinuada, a menos que o médico que a prescreve dê instruções nesse sentido. Medidas hemostáticas locais demonstraram ser suficientes para controlar potenciais problemas de sangramento resultantes do tratamento odontológico.

Perfil dos pacientes em uso de anticoagulantes orais diretos atendidos via judicial em um município de médio porte do estado de Minas Gerais / Profile of patients in the use of direct oral anticoagulants assisted judicially in a medium-sized municipality of the state of Minas Gerais

Fundamentos: O sistema de saúde brasileiro é embasado nos princípios estabelecidos na Constituição Federal, que in-cluem igualdade, universalidade, equidade e participação popular, em um modelo de saúde totalmente gratuito. O Brasil vive um grande desafio para ofertar assistência de qualidade para toda população. Muitas vezes, é necessário solicitar à justiça um suporte para conseguir acesso à saúde pública. Entre os processos judiciais envolvendo questões de saúde, a maioria são referentes ao fornecimento de medicamentos. Dentre os medicamentos solicitados, destacam-se os anticoagulantes orais diretos (DOACs), cujos estudos apontam que apresentam melhor segurança e eficácia similar em relação à varfarina, medicamento padronizado no SUS para o tratamento do tromboembolismo venoso e fibrilação atrial. Objetivo: Avaliar o perfil dos pacientes e das solicitações dos DOACs atendidos por via judicial. Métodos: Estudo documental descritivo realizado em Divinópolis/MG a partir de todos os processos julgados com parecer favorável pela justiça referentes à solicitação dos DOACs. A coleta de dados foi realizada em três fontes secundárias: os pro-cessos judiciários, prontuários dos pacientes nas unidades básicas de saúde e no Sistema de Informações em Saúde. Resultados: Foram incluídos no estudo um total de 74 processos referentes à solicitação dos DOACs no município de Divinópolis-MG. Observou-se que 74,3% dos indivíduos eram do sexo feminino, com média de idade de 70 anos. O diagnóstico mais observado foi a fibrilação atrial (36,5%). Cerca de 52,7% dos médicos registraram que houve tenta-tiva terapêutica com varfarina antes da introdução dos DOACs e a comodidade (24,3%) foi a justificativa mais utilizada por optar pelos DOACs seguida por dificuldade em controlar a RNI (20,3%). Outro dado encontrado foi que 25,7% dos pacientes nunca obtiveram na farmácia do SUS o medicamento solicitado por via judicial. Conclusão: Concluímos que a demanda judicial que afoga tanto o sistema judiciário como o sistema de saúde, poderia ser evitada se fossem seguidas as recomendações da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde para estabelecer a distribuição dos insumos de saúde. Além disso, nos processos judiciais faltam informações importantes para auxiliar o juiz a emitir um parecer, sendo baseadas, na maioria das vezes, em apenas uma opinião médica. (AU)

Fundamentals: The Brazilian health system is based on the principles established in the Federal Constitution, which include equality, universality, equity, and popular participation in a completely free health model. Brazil is under great challenge to offer quality care to the entire population. It is often necessary to ask the court for support to gain access to public health.Among the court proceedings involving health issues, the majority refer to the supply of medicines. Among the drugs requested, direct oral anticoagulants (DOACs) stand out, which indicate that they have better safety and similar efficacy concerning warfarin, a standardized medication in the SUS to treat venous thromboembolism (VTE) and atrial fibrillation (AF). Objective: Assess the profile of patients and requests for direct oral anticoagulants (DOACs) served by the court. Methods: Descriptive documental study carried out in Divinópolis/MG from all cases judged with a favorable opinion by the court regarding the request of DOACs. Data collection was carried out from three secondary sources: court proceedings, medical records of patients in basic health units, and the Health Information System (SIS). Results:A total of 74 lawsuits referring to the DOACs request in the city of Divinópolis-MG were included in the study. It was observed that 74.3% of the individuals were female, with a mean age of 70 years. The most common diagnosis was atrial fibrillation (36.5%). About 52.7% of physicians reported that there was a therapeutic attempt with warfarin before the introduction of DOACs, and convenience (24.3%) was the most used justification for choosing DOACs, followed by difficulty in controlling the INR (20.3%). Another finding was that 25.7% of the patients never obtained the medication requested through the courts at the SUS pharmacy. Conclusion: We concluded that the judicial demand that drowns both the judicial system and the health system could be avoided if the recommendations of the National Commission for the Incorporation of Technologies in the Unified Health System were followed to establish the distribution of health education. In addition, in court proceedings, important information is lacking to assist the judge in issuing an opinion and is most often based on only one medical opinion. (AU)

Relación entre la presión arterial y el control de la hemorragia post-exodoncia en pacientes bajo tratamiento con warfarina / Relationship between blood pressure and hemorrhage control post exodontia in patients under warfarin treatment

Objetivo: Determinar la relación entre el nivel de pre- sión arterial (PA) y la hemorragia post-exodoncia aplicando medidas de hemostasia local en pacientes bajo tratamiento con warfarina. Materiales y métodos: Este estudio se realizó sobre 30 pacientes (15 hombres y 15 mujeres) bajo tratamiento anti- coagulante oral (TACO) con warfarina. Los pacientes concu- rrían al programa de TACO del Hospital y Centro de Referen- cia de Salud El Pino (HEP y CRS). Se les realizaron una o dos extracciones dentales (n=38) sin suspensión del anticoagulan- te oral a pacientes que tuvieran un coeficiente internacional normalizado (INR) del día menor o igual a 3. Se aplicaron medidas de hemostasia local con gasa compresiva y/o sutura en 30 de las extracciones dentales. Los procedimientos quirúr- gicos fueron llevados a cabo en el Servicio Dental del CRS y HEP. Se registraron las siguientes variables: 1) PA previa a la exodoncia, 2) PA a los 30 minutos, 3) Presencia o ausencia de hemorragia a los 30 minutos post-exodoncia y 4) PA y presen- cia o ausencia de hemorragia a las 24 horas post-exodoncia. Se estudió la relación entre el nivel de PA y la hemorragia post-exodoncia. Resultados: De todos los pacientes evaluados, ninguno presentó hemorragia post-exodoncia en los distintos momen- tos de evaluación, independientemente de cuál fuera su PA. No se encontraron efectos de la variable PA ­considerando valores de PA sistólica (PAS) por debajo de 140 mmHg y de PA diastólica (PAD) menores a 90 mmHg- en relación con la hemorragia post-exodoncia. Conclusión: De acuerdo con los resultados obtenidos en este estudio, la presión arterial con PAS <140 mmHg y PAD <90 mmHg no es un factor que influya en el sangrado post-exodoncia en pacientes bajo tratamiento con warfarina con ≤3 (AU)

Aim: To establish the relationship between blood pres- sure (BP) level and post-exodontic hemorrhage by applying local hemostasis measures in patients under warfarin treat- ment. Materials and methods: This study was conducted in 30 patients (15 men and 15 women) under oral anticoagu- lant (OAC) treatment with warfarin. The patients attended the TACO program of the "Hospital y Centro de Referencia de Salud el Pino (HEP y CRS)". One or two dental extractions (n=38) were performed in the patients that had an INR low- er or equal to 3, without suspending the oral anticoagulant treatment, applying local hemostasis measures with compres- sive gauze and/or suture in 30 of the extractions. The surgical procedure was carried out in the Dental Department of the CRS and HEP. The following variables were registered: 1) BP prior to extraction, 2) BP after 30 minutes, 3) presence or absence of hemorrhage after 30 minutes post-exodontia and 4) BP and presence or absence of hemorrhage 24 hours post-exodontia. The relation between BP level and post-exo- dontic bleeding was studied. Results: Considering all the examined patients, none of them presented post-exodontic hemorrhage at any of the dif- ferent moments of evaluation, regardless of their BP level. No effect of the BP variable ­considering a range of systolic BP SBP) below 140 mmHg and a diastolic BP (DBP) under 90 mmHg- was found in relation to post-exodontic hemorrhage. Conclusion: According to the results obtained in this study, blood pressure with SBP <140 mmHg and DBP <90 mmHg is not an influential factor in post-exodontic bleeding in patients under warfarin treatment with ≤3 (AU)

Como realizar o manejo do paciente anticoagulado com Varfarina no pré, trans e pós-operatório / How to manage the anticoagulated patient with Warfarin in the pre, trans and postoperative period

A Varfarina é um anticoagulante da classe dos antagonistas da vitamina K que atua prevenindo a formação e a expansão do coágulo sanguíneo. É indicada para indivíduos com risco de trombose, pacientes pós-acidentes vasculares isquêmicos e portadores de trombofilias, dentre outros. O manejo do paciente anticoagulado pode gerar dúvidas, devido ao risco de complicações hemorrágicas ou da ocorrência de eventos tromboembólicos. Este trabalho visa orientar, de forma direta, o acadêmico e profissional de odontologia, diante de pacientes em uso de Varfarina.

Warfarin is an anticoagulant in the class of vitamin K antagonists that works by preventing the formation and expansion of the blood clot. It is indicated for individuals at risk of thrombosis, ischemic post-stroke patients and patients with thrombophilia, among others. The management of anticoagulated patients may raise doubts, due to the risk of hemorrhagic complications or the occurrence of thromboembolic events. This work aims to direct, directly, the academic and professional of dentistry, before patients using Warfarin.

Notas técnicas para judicialização de anticoagulantes orais diretos: uma avaliação do perfil / Technical notes for judicialization of direct oral anticoagulants: a profile assessment

Fundamentos: A judicialização da saúde no Brasil gera aumento anual significativo das demandas por recursos financei-ros. Em 2016, com intuito de promover uma comunicação entre o sistema jurídico e o sistema de saúde, implementaram o sistema e-NatJus (Núcleos de Apoio Técnico do Poder Judiciário). A função do e-NatJus é fornecer apoio técnico aos juízes nas questões relativas à saúde por meio da elaboração de Notas Técnicas (NT). Objetivo: Analisar o perfil e a qualidade das NT de solicitação de anticoagulantes orais diretos (DOACs) disponíveis no portal eletrônico do e-NatJus para consultas por juízes. Métodos: Trata-se de um estudo documental descritivo, em que foram avaliadas as características sociodemo-gráficas, do diagnóstico e tratamento dos pacientes, bem como informações sobre as evidências da eficácia e segurança da tecnologia e conclusão de todas as NT referentes à solicitação de DOACs obtidas na plataforma e-NatJus desde sua im-plantação em 2018 até junho de 2020. Resultados: Foram incluídas no estudo 181 NT: rivaroxabana (67,0%), apixabana (16,0%), dabigatrana (12,0%) e edoxabana (5,0%). A média de idade dos indivíduos foi de 65,7 (±15,1) anos, sendo, (50,3%) do sexo feminino. São Sebastião do Paraíso foi o município que mais solicitou apoio nas NT (5,0%), e o estado com mais solicitações foi Santa Catarina (34,8%). Em relação ao diagnóstico dos pacientes, os mais prevalentes foram fibrilação atrial (FA)(31,5%) e troembolismo venoso (TEV)(16,4%). Aproximadamente 86 NT estavam com conteúdo semelhante no item evidência científica. Observou-se que (57,5%) tiveram a conclusão não favorável para disponibilizar o medicamento solicitado. Dentre as 77 NT que tiveram a conclusão favorável, (57,1%) não avaliaram as recomendações da Comissão Na-cional de Incorporação de Tecnologias (CONITEC). Conclusão: De forma geral, nosso estudo permitiu conhecer o perfil das NT e os principais motivos de solicitações dos DOACs, com intuito de compreender melhor se são realizadas realmente de forma consciente e responsável. A população que solicitou os DOACs via judicial é uma população idosa e não houve grande diferença entre os sexos. Os diagnósticos mais prevalentes nas NT foram FA e TEV corroborando com a indicação desses medicamentos. Pode-se observar que a maioria das NT que concedeu parecer favorável não evidenciou consulta à CONITEC e não apresentou evidência científica que contemplava de forma concreta sua decisão (AU)

Background: The judicialization of health in Brazil generates an annual increase in demands for financial resources. In 2016, to promote communication between the legal system and the health system, the implementation of e-NatJus system (Technical Support Centers of the Judiciary). The role of e-NatJus is to provide technical support to judges on health-related issues through the preparation of Technical Notes (NT). Objective: Analyze the profile and quality of TNs requesting Direct Oral Anticoagulants (DOACs) available on the e-NatJus electronic portal for consultation by judges. Methods: This is a descriptive documentary study, which evaluated the sociodemographic characteristics, diagnosis, and treatment of patients, as well as information on the evidence of the efficacy and safety of technology and the conclusion of all NT related to the request for DOACs obtained in the e-NatJus platform since its implementation in 2018 to June 24, 2020. Results: The study included 181 NT: rivaroxaban (67,0%), apixaban (16,0%), dabigatran (12,0%), and edoxaban (5,0%). The mean age of the individuals was 65.7 (±15.1) years, being (50,3%) female. São Sebastião do Paraíso was the municipality that most requested support in the NT (5,0%), and the state with the most requests was Santa Catarina (34,8%). Regarding the diagnosis, the most prevalent patients were AF (31,5%) and VTE (16,4%). Approximately 86 NT had similar content in the scientific evidence item. It was observed that (57,5%) had an unfavorable conclusion about making the requested drug available. Among the 77 NT that had a favorable conclusion, (57,1%) did not evaluate the rec-ommendations of the National Commission for the Incorporation of Technologies (CONITEC). Conclusion: In general, our study is effective to know the profile of the NT and the main reasons for consulting DOACs, to better understand the form of knowledge and the DOACs. It can be observed that most NTs granted a favorable opinion, did not evidence CONITEC and did not present scientific evidence that contemplated the concrete form of their decision (AU)

Predictors of Hospitalization in Vitamin K Antagonist Users Presenting with Bleeding at the Emergency Department

Abstract Background Vitamin K antagonists (VKA) are indicated for the prevention of thromboembolic events and reduction of mortality in patients with atrial fibrillation and patients with valvular prostheses. However, their use is associated with bleeding complications and hospitalizations. Predictors of hospital admission for bleeding in these patients are poorly known. Objectives To define the predictors for hospitalization of VKA users who seek emergency care due to bleeding. Methods Single-center, cross-sectional study, with retrospective analysis of electronic medical records from 03/01/2012 to 02/27/2017. Clinical and laboratory variables were compared between patients who were hospitalized and those who were not. A logistic regression model as used, in which the variables were included using the Backward stepwise method, with a p value of 0.05 as the input criterion, a removal value of 0.20 and a confidence interval of 95%. The p-value was considered statistically significant when <0.05. Results A total of 510 patients with bleeding were included, of whom 158 were hospitalized. Predictors of hospitalization were: INR at supratherapeutic levels (OR 3.45; P <0.01; 95% CI 1.58 - 7.51), gastrointestinal bleeding (OR 2.36; P <0.01; CI 95% 1.24 - 4.50), drop in hemoglobin (OR 6.93; P <0.01; 95% CI 3.67 - 13.07), heart failure (OR 1.96; P 0.01; 95% CI 1.16 - 3.30) and need for blood transfusion (OR 8.03; P <0.01; 95% CI 2.98 - 21.64). Conclusion Drop in hemoglobin, heart failure, INR at supratherapeutic levels, gastrointestinal bleeding and need for blood transfusion were associated with hospitalization. Identification of these factors in the initial evaluation would help to define which patients will demand more intensive care.

Bleeding associated with self-medication in warfarin users: A prospective observational study in Ijuí (Brazil)

Abstract Warfarin has been associated with bleeding and venous thromboembolism. Objective: This study aimed to estimate the association between bleeding and concomitant self-medication, and the incidence of adverse drug reactions in patients using warfarin. Setting: the public health network of Ijuí, a municipality in southern Brazil. This was an open prospective cohort, conducted for a period of 18 months with users of warfarin, treated at the public health service. The association between bleeding and self-medication was evaluated by means of the Cox Model with left truncation, using the time variable. Main outcome measurement: bleeding reported in the follow-up. Cases of thromboembolism and death were also registered. All patients treated with warfarin in the public health system of the municipality (98) were identified. Sixty-eight were interviewed and followed up, of whom 63 completed follow-up and five died during the study. Bleeding rates of 37.7 /100 patients/year, thromboembolism of 4.8/100 patients / year and deaths of 4.8 /100 patients / year were observed. The results showed that patients, who take warfarin and self-medicated present a two-fold increased bleeding, compared with those who do not self-medicate. The bleeding risk associated with self-medication ranged from 2.001 to 2.685; those values maintained their significance even when adjusted for number of interactions, CYP polymorphism, TTR and age in COX analysis. These results greatly suggest the need for providing greater assistance to patients who take anticoagulant medications with the purpose of reducing self-medication and consequently, adverse reactions.

Riesgo de sangrado en pacientes anticoagulados con antagonistas de la vitamina K que reciben antibióticos / Risk of bleeding in anticoagulated patients with vitamin K antagonists who receive antibiotics

Lograr un adecuado nivel de anticoagulación con antagonistas orales de la vitamina K suele ser un desafío frecuente en la práctica clínica, dado que su estrecho rango terapéutico suele verse afectado por diversas interacciones farmacológicas,alimentos y condiciones clínicas. A partir de un caso de un paciente anticoagulado que presenta una hemorragia gastro-intestinal posterior a realizar un tratamiento antibiótico, la autora de este artículo revisó la evidencia sobre el riesgo desangrado secundario a la interacción entre este tipo de anticoagulantes y antibióticos orales. Su conclusión tras realizar una búsqueda bibliográfica y seleccionar la mejor evidencia disponible, es que existe un aumento del riesgo relativo desangrado en pacientes anticoagulados que reciben antibióticos, por lo que deberían evitarse aquellos antibióticos con conocido potencial de interacción. Si ello no fuera posible, se recomienda monitorizar el estado de anticoagulación con dosaje de la razón internacional normatizada (RIN) posterior a la introducción del antibiótico. (AU)

Achieving an adequate level of anticoagulation with oral vitamin K antagonists is often a frequent challenge in clinical practice, given that their narrow therapeutic range is often affected by various drug interactions, food, and clinical conditions. Based on a case of an anticoagulated patient who presented gastrointestinal bleeding after antibiotic treatment, the authorof this article reviewed the evidence on the risk of secondary bleeding due to the interaction between this type of anticoagulants and oral antibiotics. Their conclusion, after performing a literature search and selecting the best available evidence, is that there is an increased relative risk of bleeding in anticoagulated patients receiving antibiotics, so antibiotics with known potential for interaction should be avoided. If it weren't possible, it is recommended to monitor the anticoagulation status with International Normalized Ratio (INR) dosing after the introduction of the antibiotic. (AU)

Use of a mobile application for the control of anticoagulation with warfarin: a cluster randomized controlled clinical trial - Ijui/RS/Brazil

Abstract To evaluate the effectiveness of an anticoagulation protocol adapted in a mobile application (appG) for patients using warfarin. This was a cluster randomized controlled clinical trial carried out in basic health centers of Ijui, RS, Brazil, between April and October 2017. The appG was installed on the cell phones of all physicians belonging to the intervention group. Primary outcomes were bleeding and thrombosis, and secondary outcomes were changes in the dose of warfarin, use of new drugs, drug interactions, search for health services, and remaining on the target international normalized ratio. Thirty-three patients belonging to 11 basic health centers were included in this study. From these, 15 patients were in the intervention group which used the appG, and 18 were in the control group. After 6 months, patients in the appG group had fewer bleeding events (7% versus 50%, p-value=0.028) and a lower weekly dose of warfarin (29.3 ± 9.7 mg versus 41.7 ± 12.5 mg, p-value=0.030) when compared to the control group. The anticoagulation protocol adapted in a mobile app reduced bleeding in patients using warfarin.

Tiempo en rango terapéutico en pacientes con fibrilación auricular anticoagulados con warfarina en el Instituto Nacional del Tórax / Time in therapeutic range in patients with atrial fibrillation anticoagulated with warfarin at the Instituto Nacional de Torax

INTRODUCCIÓN: la fibrilación auricular es la arritmia más frecuente, siendo una patología trombogénica, por lo que en la mayoría de los casos es necesaria la anticoagulación. Uno de los agentes más usados es la warfarina y su efecto se determina mediante el INR y el tiempo que el paciente se mantiene en rango terapéutico, denominado Tiempo en Rango Terapéutico. OBJETIVO: determinar el Tiempo en Rango Terapéutico en pacientes con Fibrilación Auricular que acuden a consulta externa de cardiología en el Instituto Nacional del Tórax MATERIALES Y MÉTODOS: se hizo la revisión de expedientes clínicos de pacientes que acudieron a consulta externa de cardiología con fibrilación auricular de 2017 a 2019 y se calculó el TTR mediante el método de Rosendaal y porcentaje de INRs en rango terapéutico RESULTADOS: de 212 pacientes dentro del universo se incluyeron en el estudio 49 pacientes. La edad promedio fue de 67,49 ±12,33 años, con un 63,3% de pacientes de sexo femenino. El TTR calculado por método de Rosendaal fue de 34±25,98% y el TTR calculado por porcentaje de INRs en rango fue de 31,31±24,01%. El porcentaje de pacientes con TTR adecuado (≥70%) fue del 10,2%. CONCLUSIÓN: los pacientes con fibrilación auricular anticoagulados con warfarina que acuden a consulta externa de cardiología del Instituto Nacional del Tórax presentan un nivel inadecuado de Tiempo en rango terapéutico. (AU)

INTRODUCTION: atrial fibrillation is the most frequent arrhythmia, being a thrombogenic pathology, so anticoagulation is necessary in most cases. One of the most used agents is warfarin and its effect is determined by the INR and the time that the patient remains in the therapeutic range, called Time in Therapeutic Range OBJECTIVE: to determine the Time in Therapeutic Range in patients with Atrial Fibrillation who attend outpatient cardiology consultation at the Instituto Nacional del Tórax MATERIALS AND METHODS: the clinical records of patients who attended the outpatient cardiology consultation with atrial fibrillation from 2017 to 2019 were reviewed and the TTR was calculated using the Rosendaal method and percentage of INRs in the therapeutic range RESULTS: of 212 patients within the universe, 49 patients were included in the study. The average age was 67.49 ± 12.33 years, with 63.3% of female patients. The TTR calculated by the Rosendaal method was 34 ± 25.98% and the TTR calculated by percentage of INRs in range was 31.31 ± 24.01%. The percentage of patients with adequate TTR (≥70%) was 10.2%. CONCLUSION: patients with atrial fibrillation anticoagulated with warfarin who attend the outpatient clinic of cardiology of the Instituto Nacional del Tórax present an inadequate level of Time in therapeutic range.(AU)

Características de pacientes atendidos en dos clínicas de anticoagulación de Colombia / Characteristics of patients in two anticoagulation clinics in Colombia

Resumen Objetivo: Establecer las características demográficas, clínicas y terapéuticas de los pacientes anticoagulados atendidos en las clínicas de anticoagulación del Hospital Universitario Fundación Santa Fe de Bogotá (HUFSFB) y del Hospital Universitario San Vicente Fundación Medellín (HUSVF), en los años 2015 y 2016. Método: Se realizó un estudio descriptivo, retrospectivo y transversal. La población de referencia la conformaron los pacientes atendidos en las clínicas de anticoagulación del HUSVF y el HUFSFB en el periodo comprendido entre marzo de 2015 y marzo de 2016. La información se tomó de los registros clínicos de ambos hospitales y para el análisis se utilizó estadística descriptiva. Resultados: Se evaluaron 502 pacientes en las dos clínicas de anticoagulación, con una edad promedio de 64 años en el HUFSFB y de 61 años en el HUSVF. La principal indicación de anticoagulación fue fibrilación o flutter auricular en el HUSVF (46.5%) y enfermedad tromboembólica venosa en el HUFSFB (69.7%). El 100% de los pacientes del HUSVF fueron anticoagulados con warfarina, frente a solo el 23% de los del HUFSFB; el tiempo en rango terapéutico fue del 69% en el HUFSFB y del 55% en el HSVF. Se presentó retrombosis en tres pacientes en cada una de las instituciones, y los eventos de sangrado fueron 7 (3,8%) en el HUFSFB y 30 (9,3%) en el HUSVF. Conclusiones: Las diferencias administrativas entre las dos instituciones se ven reflejadas en los resultados obtenidos. Existe, ligada al sistema de salud de nuestro país, una gran diferencia en la población, las enfermedades y el acceso a los servicios y a los medicamentos.

Abstract Objective: To establish the demographic, clinical and therapeutic characteristics of the anticoagulated patients treated at the anticoagulation clinics of Fundación Santa Fe de Bogotá (HUSVF) and Hospital Universitario San Vicente Fundación Medellin (HUFSFB), between 2015 and 2016. Method: A transversal retrospective descriptive study was carried out. The reference population consist in patients treated in the anticoagulation clinics of the HUSVF in Medellin and the HUFSFB in Bogotá between March 2015 to 2016. The information was taken from the clinical records of both hospitals and descriptive statistics were used for the data analysis. Results: A total of 502 patients were evaluated in both anticoagulation clinics. Patients' average age in HUFSFB was 64 years while in HUSVF was 61; the main pathology that required anticoagulation was the fibrillation/auricular flutter in HUSVF (46,5%) and venous thromboembolic disease in HUFSFB (69.7%). 100% of HUSVF patients are anticoagulated using warfarin and only 23% of those in HUFSFB; the time in therapeutic range (TTR) was 69% in HUFSFB and 55% in HSVF. Re-thrombosis was presented in 3 patients in each of the institutions and the bleeding events were 7 (3.8%) in HUFSFB and 30 (9.3%) in HUSVF. Conclusions: The administrative differences between the two institutions are reflected in the results obtained; there is a great difference in the population, pathologies, access to services and medicines, linked to the health system of our country.

Atrial Fibrillation and Use of Rivaroxaban: Performance of the Prothrombin Time / INR as a Function of Time After Blood Collection

Abstract Background Traditionally, the most effective therapy in the prevention of stroke in patients with atrial fibrillation (AF) has been oral anticoagulation with vitamin K inhibitors, particularly warfarin, whose disadvantages and adverse effects have led to their replacement by "direct oral anticoagulants", as factor X inhibitor. Objectives This study aimed to conduct a brief approach on atrial fibrillation (AF) and use of Rivaroxaban, and to comparatively evaluate the prothrombin time / International Normalized Ratio (PT/INR) in patients with AF in use of this oral anticoagulant, depending on the time elapsed between the last administration of the drug and the time of blood sample venipuncture. Methods We evaluated 34 patients with AF in use of Rivaroxaban by using PT / INR, distributed into a subgroup with blood collection time ≤ 12 hours (n = 7) and > 12 hours after the last drug intake (n = 27). Mann-Whitney test was used to compare the groups and p < 0.05 was considered significant. Results An analysis as a function of time between the Rivaroxaban intake and blood collection, revealed that PT / INR suffers the greatest effect up to 12 hours after ingestion of the drug, dropping to levels close to normal in subsequent hours before the next dose. Conclusion We concluded that, in contrast to warfarin, the knowledge of the time interval between drug intake and blood collection from patients taking Rivaroxaban is essential to properly interpret a laboratory test to assess hemostasis, particularly PT and its derivatives. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Mortalidad y hospitalización en una consulta de anticoagulación y trombosis: Experiencia del Centro Cardiovascular Regional Ascardio / Mortality and hospitalization of an anticoagulation and thrombosis consult experience from the Centro Cardiovascular Regional Ascardio

El tratamiento anticoagulante oral con fármacos inhibidores de la vitamina K como la warfarina se viene utilizando desde hace décadas para la terapia y prevención de la enfermedad tromboembólica con efectos secundarios ampliamente conocidos, pero con una utilidad clínica bien contrastada. El objetivo de este estudio fue determinar la proporción de mortalidad y hospitalización de la consulta de anticoagulación y trombosis del Centro Cardiovascular Regional ASCARDIO en el año 2017 para lo cual se realizó un estudio descriptivo transversal que incluyó una muestra de 294 pacientes. La principal indicación de anticoagulación fue la fibrilación auricular (73%) seguida de la enfermedad tromboembólica venosa (13%) e isquemia miocárdica (9%). Se registró una mortalidad de 11,7% siendo la principal causa de muerte de origen cardíaco (58%). La edad promedio de los pacientes fallecidos fue de 65 años, siendo 53% del sexo femenino; para el momento de la muerte, el 65% de los pacientes estaba tomando warfarina. La hospitalización se observó en el 10% de la muestra siendo la principal causa de la misma la cardíaca (60%) seguida de causas hemorrágicas (18%); de los pacientes hospitalizados, la edad promedio fue de 66 años siendo 52% del sexo femenino; el 90% de los pacientes estaba tomando warfarina al momento de la hospitalización. El análisis de riesgo para mortalidad y hospitalización según causa y estatus de warfarina no mostró significancia estadística. No se evidenció relación de riesgo estadísticamente significativa entre muerte, hospitalización y estatus de la warfarina. Hubo mayor proporción de muertes (45%) y hospitalización (17%) en el grupo que ingresó con diagnóstico de isquemia miocárdica(AU)

Oral anticoagulant treatment with vitamin K inhibitor drugs such as warfarin has been used for decades for the therapy and prevention of thromboembolic disease with widely known side effects but with well-proven clinical utility. To determine the proportion of mortality and hospitalization of the anticoagulation and thrombosis clinic of the ASCARDIO Regional Cardiovascular Center in 2017 a descriptive cross-sectional study was carried out that included a sample of 294 patients. The results show that the main indication for anticoagulation was atrial fibrillation (73%) followed by venous thromboembolic disease (13%) and myocardial ischemia (9%). An 11.7% mortality rate was observed. The mean age of the deceased was 65 years with a slight prevalence of the female sex (53%). The main cause of death was cardiac (58%) and 65% of the deceased patients were taking warfarin at the moment of death. A 10% hospitalization rate was observed with an average age of hospitalized patients of 66 years; 52% were females. The main cause of hospitalization was cardiac (60%) followed by hemorrhage (18%) and 90% of the patients were taking warfarin at the time of hospitalization. The risk analysis for mortality and hospitalization according to cause and status of warfarin did not show statistical significance. There was a higher proportion of deaths (45%) and hospitalization (17%) in the group admitted with a diagnosis of myocardial ischemia(AU)

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil / Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Abstract Background Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. Objectives To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). Methods Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. Results 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). Conclusions An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Resumo Contexto Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. Objetivos Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. Métodos Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. Resultados Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). Conclusões Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil / Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Abstract Background Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. Objectives To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). Methods Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. Results 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). Conclusions An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Resumo Contexto Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. Objetivos Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. Métodos Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. Resultados Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). Conclusões Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.