Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism / Uso bem-sucedido de rivaroxabana com níveis terapêuticos de antifator xa em paciente com obesidade mórbida e embolia pulmonar aguda de risco intermediário-alto

Abstract Direct oral anticoagulants (DOACs) have become the standard of care for acute and long-term therapy for venous thromboembolism (VTE) due to their efficacy and safety profiles. The 2021 International Society on Thrombosis and Haemostasis guidelines recommend using standard DOAC dosages in patients with BMI >40 kg/m2 or weight >120 kg. Use of DOACs remains uncertain in morbidly obese patients with VTE, including acute PE. A morbidly obese woman in her 30s who presented with acute worsening of dyspnea was diagnosed with acute intermediate-high risk acute pulmonary embolism and concomitant proximal deep vein thrombosis, constituting a clinically challenging scenario for treating her with rivaroxaban. Standard doses of rivaroxaban for acute and extended phase treatment of venous thromboembolism in individuals with morbid obesity at BMI>70 kg/m2 may be effective, and safe.

Resumo Devido à sua eficácia e aos seus perfis de segurança, os anticoagulantes orais diretos (DOACs) tornaram-se o padrão de cuidado para a terapia aguda e de longo prazo de tromboembolismo venoso (TEV). As diretrizes da Sociedade Internacional de Trombose e Hemostasia de 2021 recomendam o uso de dosagens padrão de DOACs em pacientes com índice de massa corporal (IMC) > 40 kg/m2 ou peso > 120 kg. O uso de DOACs em pacientes com obesidade mórbida e TEV, incluindo embolia pulmonar aguda, ainda não foi esclarecido. Uma mulher com obesidade mórbida na faixa dos 30 anos que apresentou piora aguda da dispneia foi diagnosticada com embolia pulmonar aguda de risco intermediário-alto e trombose venosa profunda proximal concomitante, com o cenário clínico desafiador de tratá-la com rivaroxabana. Doses padrão de rivaroxabana para tratamento e recorrência de tromboembolismo venoso em indivíduos com obesidade mórbida e IMC > 70 kg/m2 podem ser eficazes e seguras.

Efficacy and safety of new oral anticoagulants in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of new oral anticoagulants （NOACs） in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion （LAAO）. METHODS Retrieved from PubMed， Embase， Web of Science， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about NOACs （trial group） versus warfarin or dual antiplatelet agents （control group） were collected during the inception and November 2022. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 10 studies were included， involving 2 RCTs and 8 cohort studies， with a total of 2 653 patients. RCT results showed that there was no statistically significant difference in the incidence of device-related thrombosis （DRT）， stroke/ systemic embolism （SSE）， major bleeding events， total bleeding events or all-cause mortality between 2 groups （P＞0.05）. Results of cohort studies showed that compared with dual antiplatelet agents， there was no statistically significant difference in the incidence of DRT， stroke/SSE， major bleeding events or all-cause mortality in the trial group （P＞0.05）. Compared with warfarin， the incidence of DRT [RR＝0.40， 95%CI　（0.19，0.82）， P＝0.01] and total bleeding events [RR＝0.28， 95%CI　（0.18， 0.44）， P＜ 0.000 01] in the trial group were decreased significantly； there was no statistical significance in the incidence of stroke/SSE， major bleeding events or all-cause mortality （P＞0.05）. CONCLUSIONS For patients with nonvalvular atrial fibrillation after LAAO， NOACs have comparable antithrombotic efficacy and safety with dual antiplatelet agents， and the incidence of DRT and total bleeding events are lower than warfarin.

Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulants and Their Use in Special Populations / 中山大学学报(医学科学版)

In the past few decades， heparin and warfarin have been the main anticoagulants used to treat and prevent venous thromboembolism. Recent studies at home and abroad have shown that non-vitamin K antagonist oral anticoagulants （NOACs） have similar or better efficacy and safety in the prevention and treatment of venous thromboembolism and non-valvular atrial fibrillation. NOACs do not require routine coagulation monitoring when used at a fixed dose. However， in special populations or specific scenarios such as emergency surgery， etc.， an overdose or underdose and abnormal metabolism of NOACs may reduce the drug efficacy and safety， so monitoring and evaluating the anticoagulant effect of NOACs is more conducive to the prognosis of patients.This paper briefly reviewed the common laboratory monitoring methods of NOACs and their use in special populations， aiming to explain different monitoring methods for different NOACs and the applicability of NOACs in special populations， and hoping to provide reference for clinical standard monitoring and use of NOACS.

Efficacy evaluation of novel oral anticoagulants in patients with cirrhosis accompanied with portal vein thrombosis: a meta-analysis / 中华肝脏病杂志

Objective: To analyze the safety and efficacy of using novel oral anticoagulants (rivaroxaban and others) in patients with cirrhosis accompanied with portal vein thrombosis (PVT). Methods: Clinical research literature published from the establishment of the database to June 20, 2021, was retrieved from PubMed, Web of Science, CNKI, Wanfang, and Weipu databases by combining subject terms and free words. RevMan software was used for the random group meta-analysis model. Results: In terms of PVT recanalization, the novel oral anticoagulants (such as low molecular weight heparin and others) had a higher recanalization rate than traditional anticoagulants (OR = 13.75, 95%CI 3.58-52.9, P = 0.000 1). In terms of bleeding, the novel oral anticoagulants did not increase the risk of bleeding compared with traditional anticoagulants (OR = 2.42, 95%CI 0.62-9.41, P = 0.20). Conclusion: The novel oral anticoagulant drugs are superior to traditional anticoagulants in terms of the occurrence of PVT recanalization; however, there is no statistically significant difference in terms of the occurrence of bleeding between the two groups.

Predictores de uso de anticoagulantes orales directos en tromboembolia pulmonar aguda / Predictors of use of direct oral anticoagulants in acute pulmonary embolism

Resumen Introducción: En la última década los anticoagulantes orales directos (ACOD) se incorporaron como herramienta para la anticoagulación en pacientes con tromboembolia pulmonar (TEP) aguda. Aunque tienen un mejor perfil farmacológico que los antagonistas de la vitamina K (AVK), el uso de estos fármacos no es masivo. El objetivo del presente trabajo fue evaluar el uso de ACOD en pacientes con TEP aguda y detectar determinantes de su indicación. Metodología: Análisis preespecificado del registro CONAREC XX que incorporó pacientes con TEP aguda en 64 centros de Argentina. Se realizó un análisis para detectar predictores de prescripción de ACOD al alta. Resultados: Se analizaron 579 pacientes que recibieron anticoagulación al alta hospitalaria: el 60% recibió AVK, el 21% heparinas y el 19% ACOD (de ellos, un 49% rivaroxabán, un 34% apixabán y un 17% dabigatrán). Los pacientes que recibieron ACOD tenían TEP de menor gravedad, menor riesgo de hemorragia y menos complicaciones intrahospitalarias. En el seguimiento a 30 días no hubo diferencias en mortalidad por todas las causas o sangrados. La cobertura de salud por un seguro social (odds ratio [OR] 7.45; intervalo de confianza del 95% [IC 95%]: 1.74-31.9; p < 0.01) o por cobertura privada (OR 10.5; IC 95%: 2.4-45.9; p < 0.01) fueron predictores independientes de la prescripción de ACOD al alta, y el antecedente de insuficiencia cardiaca (OR 0.19; IC 95%: 0.04-0.84; p = 0.028) y de enfermedad oncológica (OR 0.49; IC 95%: 0.27-0.89; p = 0.02) fueron predictores de no prescribirlos. Conclusiones: Uno de cada cinco supervivientes de TEP aguda recibió ACOD al egreso hospitalario en Argentina, y esto fue determinado por variables clínicas y económicas

Abstract Introduction: In the last decade, direct oral anticoagulants (DOACs) have been incorporated as an anticoagulation tool in patients with acute pulmonary thromboembolism (PTE). Although they have a better pharmacological profile than vitamin K antagonists (VKA), the use of these drugs is not massive. The objective of this study was to evaluate the use of DOACs in patients with acute PE and to detect determinants of its use. Methodology: Prespecified analysis of the CONAREC XX registry that included patients with acute PE in 64 centers in Argentina. An analysis was performed to detect predictors of DOAC prescription at discharge. Results: 579 patients who received anticoagulation at hospital discharge were analyzed: 60% received VKA, 21% heparin and 19% DOAC (of them, 49% Rivaroxaban, 34% Apixaban, and 17% Dabigatran). Patients receiving DOACs had less severe PE, lower risk of bleeding, and fewer in-hospital complications. At 30-day follow-up, there were no differences in all-cause mortality or bleeding. Health coverage by social insurance (OR 7.45, CI 95% 1.74-31.9, p < 0.01) or by private coverage (OR 10.5, CI 95% 2.4-45.9, p < 0.01) were independent predictors of DOAC prescription at discharge, and history of heart failure (OR 0.19, 95% CI 0.04-0.84, p = 0.028) and oncological disease (OR 0.49, 95% CI 0.27-0.89; p = 0.02) were predictors not prescribe them. Conclusions: One in five survivors of acute PE received DOACs at hospital discharge in Argentina, and this was determined by clinical and economic variables.

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)

Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti Xa y anti IIa / Recommendations for the practical management of the direct oral anticoagulants anti Xa and anti IIa

Resumen Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas pro piedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Abstract Direct oral anticoagulants have emerged as the drugs that have changed the man agement of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagu lants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

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)

Bilateral adrenal hemorrhage caused by anticoagulant therapy after joint replacement surgery: One case report and literature review / 中华内分泌代谢杂志

Bilateral adrenal hemorrhage is a rare cause of primary adrenal insufficiency, and bilateral adrenal hemorrhage due to anticoagulant use is even rarer. We describe the case of a 62-year-old woman receiving post total knee arthroplasty anticoagulant therapy who presented fever, vomitting, stomachache, and severe fatigue on the 8th day. It was until 4 months later that the patient was finally diagnosed with adrenal insufficiency resuting from bilateral adrenal hemorrhage, her symptoms were relieved by glucocorticoid replacement therapy. In order to promote the awareness, diagnosis, and mangement of post-surgery anticoagulants induced bilateral adrenal hemorrhage, the clinical characteristics of the reported cases were summarized and analyzed.

Efficacy and safety of new oral anticoagulants for the treatment of patients over 70 years with atrial fibrillation: A meta-analysis / 中华老年医学杂志

Objective:To systematically review the efficacy and safety of new oral anticoagulants(NOACs)for the treatment of patients over 70 years with atrial fibrillation.Methods:Studies comparing NOACs(dabigatran, rivaroxaban, apixaban, ximelagatran and edoxaban)versus warfarin for the treatment of patients over 70 years with atrial fibrillation were searched through databases including PubMed, Embase and the Cochrane Library, from the earliest electronic records to those published in March 2021.Stata15.0 software was used for meta-analysis.Results:A total of 19 studies and 215 471 patients were included.Meta-analysis results showed that, compared with warfarin, either a low-dose(110 mg)or a standard-dose(150 mg)of dabigatran reduced the risk of stroke/systemic embolism(SSE)in patients over 70 years with atrial fibrillation.A standard-dose of dabigatran did not decrease the risk of major bleeding, but a low dose was able to achieve it.A standard-dose(20 mg)of rivaroxaban could considerably reduce the risk of SSE in geriatric patients over 70 years with atrial fibrillation without increasing the risk of major bleeding.A standard-dose(5 mg)of apixaban could considerably decrease the risk of SSE and major bleeding in patients over 70 years with atrial fibrillation; A standard-dose(36 mg)of ximelagatran was as effective as warfarin in decreasing the incidence of SSE in patients over 70 years with atrial fibrillation, but could also considerably decrease the risk of major bleeding; A low-dose(15-30 mg)or a standard-dose(30-60 mg)of edoxaban decreased the incidence of SSE in patients over 70 years with atrial fibrillation, as did warfarin, but edoxaban considerably decreased the risk of major bleeding.Conclusions:Compared with warfarin, most of new oral anticoagulants show good efficacy in patients over 70 years old with atrial fibrillation, NOACs given at standard doses increase the risk of major bleeding, but at low doses can realize both efficacy and safety.

Advances in applied research of Rivaroxaban in children with thromboembolic disease / 中华实用儿科临床杂志

Rivaroxaban has been widely used for prevention and treatment of pulmonary embolism in adults due to the convenience of oral taking, rapid effect, less drug interaction, less influence by diet, no need of monitoring and fixed dose.However, its clinical application in children has been controversial.The EINSTEIN-Jr clinical trial and case reports at home and abroad have demonstrated the safety and effectiveness of Rivaroxaban in children with venous thrombus embolism.Therefore, Rivaroxaban can be considered as an alternative to standard anticoagulant therapy for children with venous thrombus embolism.This study reviews the application progress of Rivaroxaban in children with thromboembolic diseases.

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.

Experiencia con idarucizumab como agente reversor de dabigatran / Experience with idarucizumab as a reverse agent of dabigatran

Resumen Los anticoagulantes orales directos (AOD), entre ellos dabigatrán, poseen un perfil riesgo-beneficio favorable comparados con warfarina y además no requieren monitoreo del efecto anticoagulante. Sin embargo, en ocasiones de sangrado con amenaza de vida o requerimiento de procedimiento quirúrgico de emergencia, es de gran utilidad revertir inmediatamente el efecto anticoagulante. Idarucizumab, fragmento de un anticuerpo monoclonal humanizado, revierte inmediatamente el efecto de dabigatrán y es actualmente el único agente reversor de un AOD disponible en Argentina. Presentamos una serie de 8 pacientes a los que se les administró idarucizumab para revertir el efecto de dabigatrán. Todos eran mayores de 65 años, recibían 110 o 150 mg cada 12 horas de dabigatrán y 7/8 estaban anticoagulados por fibrilación auricular; tres tenían indicación discutida para AOD y otro, una dosis mayor a la recomendada. Dos requirieron reversión debido a una cirugía de urgencia, y 6 tuvieron sangrado con amenaza de vida: tres hemorragias digestivas y tres sangrados intra-craneanos (en dos ocasiones traumático). En todos los casos se observó normalización de la hemostasia quirúrgica o control de sangrado crítico. No se observaron complicaciones trombóticas posteriores a la administración del antídoto. Dos fallecieron dentro de los 30 días de la administración por causas no relacionadas con la reversión. Ninguno de nuestros pacientes requirió administración de una segunda dosis de idarucizumab. Nuestro resultado es similar a lo informado en la literatura internacional.

Abstract Direct oral anticoagulants (DOACs), among them dabigatran, have a favorable benefit-risk profile compared with warfarin, and no monitoring of the anticoagulant effect is required. However, reversing the anticoagulant effect immediately is very useful in cases of life-threatening bleeding and emergency surgical procedure requirement. Idarucizumab, a humanized monoclonal antibody fragment, is currently the only reversal agent of a DOAC available in Argentina. Idarucizumab immediately reverse the effect of dabigatran. We present a series of 8 real-life clinical cases who received idarucizumab to reverse the effect of dabigatran. All of the patients were older than 65 years, were receiving 110 or 150 mg every 12 hours of dabigatran and 7/8 were anticoagulated because of atrial fibrillation. Three had a debatable indication for DOACs and another, a higher dose than recommended. Two required reversal due to emergency surgery, and 6 cases had life-threatening bleeding: three gastrointestinal hemorrhages and three intracranial bleeding (Two had a head trauma). In all cases normalization of surgical hemostasis or control of critical bleeding was observed. No hemorrhagic or thrombotic complications were observed after antidote administration. Two died within 30 days of administration of idarucizumab, due to causes unrelated to the reversal. None of our patients required administration of a second dose of idarucizumab. Our result is similar to that reported in international literature.

Recomendaciones actualizadas para profilaxis de la enfermedad tromboembólica venosa en Argentina / Updated recommendations for venous thromboembolic prophylaxis in Argentina

La enfermedad tromboembólica venosa (ETV) en adultos hospitalizados posee elevada morbimortalidad, es origen de complicaciones crónicas y determina incrementos de costos para el sistema de salud. Desde la publicación de recomendaciones de tromboprofilaxis en pacientes internados en 2013, han surgido nuevas alternativas y estrategias, que nos motivaron a actualizar nuestras recomendaciones. A pesar de que existen diferentes consensos y guías de práctica clínica la adherencia a las mismas es subóptima. Se han actualizado las diferentes alternativas terapéuticas para los adultos hospitalizados (clínicos no quirúrgicos, quirúrgicos no ortopédicos, con y sin cáncer, ortopédicos y embarazadas), poniendo particular atención en los fármacos disponibles en Argentina.

Venous thromboembolic disease (VTE) in hospitalized adults has high morbidity and mortality, is the origin of chronic complications and increased cost for the health system. Since the publication of recommendations for thromboprophylaxis in hospitalized patients in 2013, new alternatives and strategies have emerged, which motivated us to update our recommendations. Although there are different consensus and clinical practice guidelines, adherence to them is suboptimal. The different therapeutic alternatives for hospitalized adult patients (non-surgical, surgical non-orthopedic, with and without cancer, orthopedic an d pregnant) have been updated, paying particular attention to the drugs available in Argentina.

Comparison between direct factor Xa inhibitors and low-molecular-weight heparin for efficacy and safety in the treatment of cancer-associated venous thromboembolism: A meta-analysis

Aim of the Study: The role of direct-acting oral anticoagulants in the treatment of venous thromboembolism (VTE) in cancer patients compared with the current standard of low-molecular-weight heparin (LMWH) treatment remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of direct factor Xa inhibitors compared with those of LMWH in the treatment of cancer-associated VTE. Materials and Methods: We systematically searched PubMed, EMBASE, Cochrane library, and Web of Science for potential randomized controlled clinical trials and retrospective cohort studies. Data on recurrent VTE (efficacy) and major and minor bleeding events (safety) were extracted, and the odds risks (OR) were analyzed using a random-effect model. Results: A total of nine studies involving 4208 cancer patients with VTE were included in these analyses. Pooled analysis showed that direct factor Xa inhibitors were significantly superior to LMWH in reducing the risk of recurrent VTE (OR = 0.67; 95% confidence interval [CI]: 0.54–0.82). There was no significant difference in the rate of major bleeding between the direct factor Xa inhibitor and LMWH treatments (OR = 1.25; 95% CI: 0.94–1.65). However, the rate of minor bleeding events was higher when a direct factor Xa inhibitor was used instead of LMWH (OR = 1.80; 95% CI: 1.05–3.07). Conclusions: Direct factor Xa inhibitors are superior to LMWH in efficacy in the treatment of VTE in cancer patients, and the safety between the two regimens is comparable except for a slightly higher rate of minor bleeding when the former is used

Advances in pharmacogenomics of new oral anticoagulants / 第二军医大学学报

Novel oral anticoagulants (NOACs) play an important role in the prevention and treatment of cardiovascular and cerebrovascular thrombosis. Different individuals have different pharmacokinetic parameters in vivo after taking the same dose of NOACs, which may be related to gene polymorphisms of transporters and metabolic enzymes involved in the in vivo process of NOACs. Compared with drug transporters, gene polymorphisms of drug metabolizing enzymes have a greater impact on the pharmacokinetic properties of NOACs, but there have been few related studies up to now. In this paper we summarized the effects of gene polymorphisms on the pharmacokinetic properties of NOACs..

A Case of Mitral Mechanical Valve Thrombosis after Switching to Edoxaban / 日本心臓血管外科学会雑誌

A 65-year-old man who had been taking warfarin for a mitral mechanical valve, was transported to our hospital for acute heart failure 3 months after switching to edoxaban. The fluoroscopy revealed restriction of the mechanical valve opening, and the catheterization showed an increased pressure gradient of the mechanical valve. The patient was diagnosed with valve thrombosis, and emergency redo mitral valve replacement was performed. The patient recovered well without complication. In cases with mechanical heart valves, sufficient explanation and education about warfarin administration is mandatory for patients' home doctors as well as patients and their families.

Data Analysis of the Risks of Abnormal Female Reproductive System Haemorrhages Induced by Novel Oral An- ticoagulants Based on FAERS / 中国药房

OBJECTIVE：To eva luate the risk of abno rmal female reproductive system haemorrhage induced by novel oral anticoagulants （NOACs）. METHODS ：The abnormal female reproductive system haemorrhage reports induced by 4 kinds of NOACs as “dabigatran etexilate ”，“rivaroxaban”，“apixaban”and“edoxaban”were used as the first suspected dugs to collected from FDA adverse event reporting system （FAERS）database during Jan. 1st，2004-May 31st，2019. The report odd ratio （ROR） method was used to detect the signal of abnormal female reproductive system haemorrhage induced by NOACs. RESULTS ：A total of 2 658 adverse events related to abnormal female reproductive system haemorrhage were collected from FAERS database ， involving 330 reports of dabigatran etexilate ，2 049 reports of rivaroxaban ，267 reports of apixaban ，and 12 reports of edoxaban. The abnormal female reproductive system haemorrhage caused by dabigatran etexilate ，apixaban and edoxaban mainly occurred in patients aged 75 and older ，accounting for 37.27％，36.70％ and 58.33％ respectively；that of rivaroxaban mainly occurred in patients with 45-64 years old ，accounting for 33.04％. The incidence of severe adverse events （SAE）induced by dabigatran etexilate，rivaroxaban，apixaban and edoxaban were 96.36％，84.53％，47.19％ and 58.33％，respectively. All of patients in the included reports were mainly hospitalized and hospitalization stay wa s prolonged ，accounting for 64.78％，90.01％，86.51％ and 71.43％ ，respectively. A total of 12 suspected signals were detected，involving cervix uteri ，fallopian tube ，ovary，pelvis cavity，uterus，vagina，urinary tract ，etc. Among them ，there were 11 positive signals of rivaroxaban ，and the bleeding events were concentrated in vaginal hematoma [ROR ＝12.07， 药。95％CI（8.51，17.12）]，postmenopausal hemorrhage [ROR ＝ 9.89，95％CI（8.31，11.77）]，pelvic hematoma [ROR ＝7.68，95％CI（5.66，10.43）]. There were 4，4 and 2 suspicious signals for dabigatran etexilate ，apixaban and edoxaban. The main bleeding events of both apixaban [ ROR＝5.18，95％CI（1.81，5.85）] and edoxaban [ROR ＝48.19，95％CI（6.76，343.77）] were vaginal hematoma ；dabigatran etexilate-induced pelvic hematoma [ROR ＝ 12.56，95％CI（8.92，17.70）] had the strongest signal ，followed by urinary tract bleeding [ROR ＝5.41，95％CI（3.34，8.76）] and pelvic hemorrhage [ ROR＝2.53，95％CI（1.88，3.40）]. CONCLUSIONS ：Totally 4 kinds of NOACs can cause abnormal female reproductive system haemorrhage ，and the incidence of SAE is high ，of requiring hospitalization or prolonging hospitalization time. The risk of haemorrhage in rivaroxaban is the highest ，usually manifesting as vaginal hematoma ，postmenopausal hemorrhage and pelvic hematoma. Dabigatran etexilate mainly induce pelvic hematoma ，while apixaban and edoxaban are mainly cause vaginal hematoma.

Research progress of antithrombotic therapy after transcatheter aortic valve implantation / 中国胸心血管外科临床杂志

@#Traditional surgical aortic valve replacement is associated with a high risk of serious complications, especially in elderly patients with other preoperative diseases and unable to undergo thoracotomy. Therefore, transcatheter aortic valve implantation (TAVI) is now the accepted standard treatment for patients with symptomatic severe aortic stenosis at elevated risk for conventional surgical valve replacement. Currently, guidelines propose the use of dual antiplatelet therapy for the prevention of thromboembolic events after TAVI in the patients without an indication for oral anticoagulation. While, this strategy is empiric and largely based on expert consensus extrapolated from the arena of percutaneous coronary intervention. Antithrombotic therapy is associated with a significant occurrence of both thrombotic and bleeding complications, thus, the balance between thrombotic and bleeding risk is critical. This review summarizes current guidelines and the evidence underpinning them and explores the rational for using antiplatelet and/or anticoagulant strategies after TAVI.