Anticoagulación precoz con warfarina en pacientes sometidos a sustitución valvular aórtica por bioprótesis: ensayo prospectivo randomizado: análisis interino / Early anticoagulation with warfarin in patients undergoing bioprosthetic aortic valve replacement: randomized prospective trial: interim analysis / Anticoagulação precoce com varfarina em pacientes submetidos à troca valvar aórtica por bioprótese: ensaio prospectivo randomizado: análise provisória

Introducción: aunque las bioprótesis son menos trombogénicas que las válvulas mecánicas; la trombosis de estas es una entidad cada vez más reconocida como causa de disfunción protésica potencialmente reversible. No está definido el beneficio de la anticoagulación rutinaria versus antiagregación plaquetaria luego de la sustitución valvular aórtica (SVA) por bioprótesis. La anticoagulación precoz podría asociarse a menores gradientes transprotésicos con similar riesgo de complicaciones. Objetivos: el objetivo primario es determinar si existe una diferencia significativa en la variación del gradiente transprotésico medio al año de la SVA entre las dos estrategias de tratamiento antitrombótico. Los objetivos secundarios son la comparación de la variación del gradiente máximo y del área valvular aórtica, y parámetros clínicos que incluyen la Clase Funcional de la New York Heart Association, las tasas de sangrado mayor y menor y la incidencia de eventos embólicos. Este trabajo representa el análisis interino a 3 meses de un proyecto a más largo plazo, y se propone mostrar los resultados preliminares de los puntos finales previamente definidos. Métodos: se presenta el análisis interino de un ensayo randomizado multicéntrico. Todos los pacientes sometidos a SVA por bioprótesis porcinas fueron sucesivamente reclutados en dos centros de cirugía cardíaca desde el 01/01/2019 hasta el 01/09/2019. El grupo anticoagulación recibió warfarina durante los primeros 3 meses y ambos recibieron aspirina a largo plazo. Se realizaron instancias de seguimiento clínicas y ecocardiográficas antes del alta, a los 3 meses y al año. Resultados: se reclutaron 107 pacientes; 46% de ellos fueron randomizados al grupo anticoagulación y 54% al grupo control. No existieron diferencias en las características basales. Tampoco existieron diferencias significativas entre ambos grupos en la variación entre el alta y los 3 meses del área valvular protésica, coeficiente de obstrucción, gradiente máximo ni gradiente medio ni en la clase funcional. En cuanto a las complicaciones, no existieron eventos embólicos y los sangrados no difirieron significativamente entre ambos grupos. Conclusiones: la anticoagulación no modificó la variación de los gradientes transprotésicos a los 3 meses. Asimismo, no produjo mayor incidencia de efectos adversos. Todavía no está dilucidado si la anticoagulación precoz con warfarina luego de la SVA tiene impacto en los resultados a largo plazo.

Introduction: although bioprostheses are less thrombogenic than mechanical valves, bioprosthesis valve thrombosis is an increasingly recognized entity that can cause potentially reversible prosthetic valve dysfunction. There is a lack of consensus whether to use anticoagulation after aortic valve replacement (AVR) or antiplatelet therapy. Our hypothesis is that early anticoagulation is associated with lower transprosthetic gradients with similar risk of complications. Objective: primary objective is to determine if there is a significant difference in the variation of the mean transprosthetic gradient (ΔGm) one year after SVA between the two antithrombotic treatment strategies. Secondary objectives are the comparison of the variation of maximum gradient and aortic valve area, and clinical parameters including NYHA functional class, major and minor bleeding rates, and the incidence of embolic events. This work represents the 3-month interim analysis of a longer-term project, and is intended to show the preliminary results of the previously defined end points. Methods: this is an interim analysis of a multicenter randomized trial. All patients who underwent AVR by porcine bioprostheses were successively recruited in two cardiac surgery centers in Montevideo between 01/01/2019 and 01/09/2019. The anticoagulation group received warfarin for 3 months. Both groups received aspirin. Clinical and echocardiographic follow-up consultations were performed before discharge, at 3 months, and at 1 year. Results: 107 patients were recruited, 46% were randomized to the anticoagulation group and 54% to the control group. There were no differences in baseline characteristics. There were no significant differences between the two groups in the variation between discharge and 3 months of effective orifice area, doppler velocity index, peak gradient and mean gradient. There were also no differences between both groups in functional class. Regarding complications, there were no embolic events and bleeding did not differ significantly. Conclusions: in this study, anticoagulation did not modify the variation of transprosthetic gradients at 3 months. Likewise, it did not produce a higher incidence of adverse effects. It remains unclear whether early anticoagulation with warfarin after AVR has an impact on long-term outcomes.

Introdução: embora as biopróteses sejam menos trombogênicas que as mecânicas, a trombose de biopróteses é uma entidade cada vez mais reconhecida como causa de disfunção protética potencialmente reversível. A anticoagulação de rotina após a substituição da valva aórtica por bioprótese (SVA) não está definida. Nossa hipótese é que a anticoagulação precoce está associada a menores gradientes transprotéticos com risco semelhante de complicações. Objetivo: o objetivo principal é determinar se há uma diferença significativa na variação do gradiente transprotético médio (ΔGm) um ano após SVA entre as duas estratégias de tratamento antitrombótico. Os objetivos secundários são a comparação da variação do gradiente máximo e da área valvar aórtica e parâmetros clínicos, incluindo NYHA CF, taxas de sangramento maior e menor e incidência de eventos embólicos. Este trabalho representa a análise intercalar de 3 meses de um projeto de longo prazo, e pretende mostrar os resultados preliminares dos pontos finais previamente definidos. Métodos: apresenta-se a análise interina de um estudo multicêntrico randomizado. Todos os pacientes submetidos a SVA por biopróteses suínas foram sucessivamente recrutados em dois centros de cirurgia cardíaca em Montevidéu, durante um período de recrutamento de 1/1/2019 a 1/9/2019. O grupo de anticoagulação recebeu warfarina por 3 meses. Ambos os grupos receberam aspirina. Foram realizadas consultas médicas clínicas e ecocardiográficas antes da alta, aos 3 meses e ao 1 ano. Resultados: foram recrutados 107 pacientes, 46% foram randomizados para o grupo anticoagulação e 54% para o grupo controle. Não houve diferenças nas características basais. Não houve diferenças significativas entre os dois grupos da variação entre alta e 3 meses na área valvar, coeficiente de obstrução, gradiente máximo ou gradiente médio. Também não houve diferenças entre os dois grupos na classe funcional. Em relação às complicações, não houve eventos embólicos e sangramentos não diferiram significativamente. Conclusões: neste estudo, a anticoagulação não modificou a variação dos gradientes transprotéticos aos 3 meses. Da mesma forma, não produziu maior incidência de efeitos adversos. Ainda não está claro se a anticoagulação precoce com varfarina após SVA tem impacto nos resultados a longo prazo.

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.

Avaliação do conhecimento sobre a terapêutica medicamentosa de indivíduos em uso de anticoagulantes orais / Evaluation of knowledge about drug therapeutics of individuals using anticoagulants / Evaluación del conocimiento sobre drogoterapéutica de personas que usan anticoagulantes

Objetivo: Avaliar o conhecimento sobre a terapêutica medicamentosa de indivíduos em uso de anticoagulantes orais. Métodos: Estudo transversal, quantitativo, com participação de 90 indivíduos em uso de anticoagulantes orais acompanhados em ambulatório de anticoagulação em Recife-PE. Os dados foram coletados de abril a julho de 2020 através de dois questionários, analisados por estatística descritiva e dispostos em tabelas. Resultados: A maioria dos indivíduos (42,2%) apresentou conhecimento adequado acerca do tratamento. Na associação do conhecimento com outras variáveis, houve significância estatística entre conhecimento adequado com resultados do International Normalized Ratio dentro da faixa indicada (p=0,001) e com idade menor que 60 anos (p=0,018), e entre conhecimento inadequado com baixa escolaridade (p=0,045), hipertensão (p=0,009) e tabagismo (p=0,041). Conclusão: A maioria dos indivíduos apresentou conhecimento adequado acerca do tratamento. Houve associação significativa entre conhecimento adequado e resultados do INR e entre a idade, assim como conhecimento inadequado e baixa escolaridade, não ser tabagista e hipertensão. (AU)

Objective: to assess knowledge about drug therapy using oral anticoagulant drugs. Methods: Cross-sectional, quantitative study, with the participation of 90 users using anticoagulants or followed up in an anticoagulation clinic in Recife-PE. Data were collected from April to July 2020 through two questionnaires, dispersed by descriptive statistics and arranged in tables. Results: Most owners (42.2%) have adequate knowledge of the treatment. In the association of knowledge with other variables, there was significance between adequate knowledge with results of the International Normalized Ratio within the given range (p = 0.001) and aged less than 60 years (p = 0.018), and between inadequate knowledge with low education (p = 0.018) p = 0.045), hypertension (p = 0.009) and smoking (p = 0.041). Conclusion: Most individuals had adequate knowledge about the treatment. There was a significant association between adequate knowledge and INR results and between age, as well as inadequate knowledge and low education, not being a smoker and hypertension. (AU)

Objetivo: Evaluar el conocimiento sobre farmacoterapia de personas que utilizan anticoagulantes orales. Métodos: Estudio transversal, cuantitativo, en el que participaron 90 personas en tratamiento con anticoagulantes orales seguidos en una clínica de anticoagulación en Recife-PE. Los datos fueron recolectados de abril a julio de 2020 a través de dos cuestionarios, analizados por estadística descriptiva y ordenados en tablas. Resultados: La mayoría de los individuos (42,2%) tenía un conocimiento adecuado sobre el tratamiento. En la asociación de conocimiento con otras variables, hubo significancia estadística entre conocimiento adecuado y resultados de la Razón Internacional Normalizada dentro del rango indicado (p = 0.001) y menor de 60 años (p = 0.018), y entre conocimiento inadecuado con baja educación (p = 0,045), hipertensión (p = 0,009) y tabaquismo (p = 0,041). Conclusión: La mayoría de las personas tenían un conocimiento adecuado sobre el tratamiento. Hubo una asociación significativa entre el conocimiento adecuado y los resultados del INR y entre la edad, así como el conocimiento inadecuado y la baja escolaridad, no ser fumador e hipertensión. (AU)

Conhecimento sobre anticoagulação oral de pacientes após correção cirúrgica de valvopatias: revisão integrativa / Conocimiento sobre la anticoagulación oral de los pacientes después de la corrección quirúrgica de valvulopatías: revisión integradora / Knowledge about oral anticoagulation of patients after surgical correction of valve diseases: integrative review

Objetivo: Verificar a existência de evidências científicas na literatura sobre o conhecimento dos pacientes em relação ao uso do anticoagulante oral após o implante de valva cardíaca metálica. Método: Revisão integrativa realizada nas bases de dados Embase, Scopus, Web of Science e Sistema Online de Busca e Análise de Literatura Médica (MEDLINE)/PubMed, utilizando descritores controlados e não controlados, sem delimitação temporal quanto à publicação, nos idiomas português, inglês e espanhol. A busca ocorreu em junho de 2022, por duas pesquisadoras de forma independente. Resultado: Verificou-se a existência de lacunas no conhecimento dos pacientes sobre os efeitos adversos relacionados ao uso dos anticoagulantes orais, às interações medicamentosas, às interações alimentares, aos fatores que interferem nos níveis do international normalized ratio e ao que deve ser feito em aso de esquecimento das doses diárias. Conclusão: A síntese elaborada enfatiza a necessidade de maior enfoque nas orientações aos pacientes sobre os anticoagulantes e suas implicações relacionadas aos hábitos de vida diária (AU)

Objective: To verify the existence of scientific evidence in the literature on patients regarding the use of oral anticoagulants after implantation of a metallic heart valve. Method: Integrative review carried out in the Embase, Scopus, Web of Science, and Online Medical Literature Search and Analysis System (MEDLINE)/PubMed databases, using controlled and uncontrolled descriptors, without temporal delimitation regarding publication, in Portuguese, English, and Spanish. The search took place in June 2022, by two researchers independently. Result: There were gaps in patients' knowledge about adverse effects related to the use of oral anticoagulants, drug interactions, food interactions, factors that interfere with international normalized ratio levels and what should be done in case of forgetting the daily doses. Conclusion: The synthesis elaborated emphasizes the need for greater focus on patient guidance on anticoagulants and their implications related to daily life habits (AU)

Objetivo: Verificar la existencia de evidencia científica en la literatura sobre el conocimiento de los pacientes sobre el uso de anticoagulantes orales después del implante de una válvula cardíaca metálica. Método: Revisión integradora realizada en las bases de datos Embase, Scopus, Web of Science y MEDLINE/PubMed, utilizando descriptores controlados y no controlados, sin delimitación temporal con respecto a la publicación, en portugués, inglés y español. La búsqueda tuvo lugar en junio de 2022, por dos investigadores de forma independiente. Resultado: Hubo lagunas en el conocimiento de los pacientes sobre los efectos adversos relacionados con el uso de anticoagulantes orales, interacciones medicamentosas, interacciones alimentarias, factores que interfieren con los niveles de la razón internacional normalizada y qué se debe hacer en caso de olvido de las dosis diarias. Conclusión: La síntesis elaborada enfatiza la necesidad de un mayor enfoque en la orientación del paciente sobre los anticoagulantes y sus implicaciones relacionadas con los hábitos de la vida diaria (AU)

Ocupação apical por endomiocardiofibrose associada a trombo diagnosticada com ecocardiografia de contraste e resolvida com tratamento clínico / Apical occupation by endomyocardiofibrosis associated with thrombus diagnosed with contrast echocardiography and resolved with clinical treatment

A endomiocardiofibrose é uma doença negligenciada e predominante em países subdesenvolvidos. Apesar de sua frequência, ainda é considerada rara. Assim, a doença é marcada pelos seguintes achados: distorção arquitetural, alterações no enchimento ventricular e alterações da mobilidade segmentar. Ela afetando não só a dinâmica diastólica e sistólica, como também as funções das válvulas cardíacas. Em uma condição mais avançada da doença, pode haver formação de trombos apicais. Neste relato de caso, revisitamos a endomiocardiofibrose, apresentando um caso desafiador de paciente do sexo feminino de 52 anos, com clínica de insuficiência cardíaca classe funcional IV da New York Heart Association. A eletrocardiografia de repouso revelou ritmo sinusal com sobrecarga do ventrículo esquerdo com vetores de alta voltagem, infradesnivelamento retificado do segmento ST e onda T negativa em região anterolateral, podendo ser compatível com padrão de strain. Já na avaliação de imagens ecocardiográficas, revelou dilatação acentuada do átrio esquerdo, com ventrículos sem dilatações e imagem de ocupação apical hiperrefringente no interior do ventrículo esquerdo, sugerindo grande trombo séssil sobreposto à capa fibrosa endocárdica. Embora a conduta cirúrgica seja a mais apoiada em literatura em tais situações, a paciente aqui apresentada recebeu tratamento com anticoagulação oral por 1 mês e 24 dias. Ela evoluiu clinicamente bem, com melhora da classe funcional da New York Heart Association e, em ecocardiografia realizada 2 meses após o início da anticoagulação oral, houve demonstração da regressão da imagem de trombo apical, apoiada com a técnica de contraste endocavitário.(AU)

Endomyocardial fibrosis (EMF) is a neglected but prevalent disease in underdeveloped countries. Despite its frequency, it is still considered a rare disease. It is marked by the following findings: architectural distortion, ventricular filling changes, and segmental mobility changes affecting not only diastolic and systolic dynamics but also heart valve function. Apical thrombi can be formed in more advanced disease. In this case report, we revisit EMF and present the challenging case of a 52-year-old woman with New York Heart Association (NYHA) functional classification (FC) IV heart failure. Resting electrocardiography revealed sinus rhythm with left ventricular (LV) overload, high voltage vectors, rectified ST-segment depression, and a negative T-wave in the anterolateral region compatible with the strain pattern. The evaluation of echocardiographic images showed marked left atrial dilation, no ventricular dilatation, and hyper-refringent apical occupation within the LV suggestive of a large sessile thrombus superimposed on the endocardial fibrous layer. Although surgery is the most supported approach in the literature in such situations, this patient was treated with oral anticoagulants (OAC) for 1 month and 24 days. The patient progressed well with an improved NYHA FC. Endocavitary contrast echocardiography performed 2 months after OAC initiation showed regression of the apical thrombus image. (AU)

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.

Profilaxis farmacológica para la prevención de la enfermedad tromboembólica en paciente con enfermedad cerebrovascular / Pharmacological prophylaxis for the prevention of thromboembolic disease in patients with cerebrovascular disease

INTRODUCCIÓN: La enfermedad cerebrovascular es un conjunto de alteraciones atribuidas a lesiones agudas y focales en el sistema nervioso central, en su mayoría secundaria a aterosclerosis DESARROLLO: En la prevención de la enfermedad cerebrovascular, existen dos grandes grupos farmacológicos, los antitromboticos y los anti plaquetarios, los cuales impactan en la calidad de vida de estos pacientes mejorando el pronóstico de los mismos. CONCLUSIONES: La enfermedad cerebrovascular comparte factores de riesgo de enfermedad tromboembólica, por lo que se recomienda iniciar profilaxis.

INTRODUCTION: Cerebrovascular disease is a group of alterations attributed to acute and focal lesions in the central nervous system, mostly secondary to atherosclerosis. DEVELOPMENT: In the prevention of cerebrovascular disease, there are two major pharmacological groups, antithrombotics and antiplatelet drugs. , which impact the quality of life of these patients, improving their prognosis. CONCLUSIONS: Cerebrovascular disease shares risk factors for thromboembolic disease, so it is recommended to start prophylaxis.

Anticoagulantes Orales de Acción Directa y sus Implicancias en la Exodoncia: Una Revisión Sistemática / Direct Acting Oral Anticoagulants and their Implications in Dental Extraction: A Systematic Review

El uso de Anticoagulantes Orales de Acción Directa (ACOD) ha aumentado considerablemente en el último tiempo. En procedimientos odontológicos, como la exodoncia, es crucial un manejo óptimo de la hemostasia de pacientes bajo tratamiento con ACOD, para equilibrar el riesgo de hemorragia y tromboembolismo. Aun no existe consenso sobre el protocolo a aplicar en pacientes con ACOD sometidos a exodoncias. El objetivo fue evaluar la necesidad de suspender o continuar el tratamiento con ACOD en pacientes sometidos a exodoncia en relación con la incidencia de episodios hemorrágicos y protocolos utilizados. Se realizó una revisión sistemática en base a los estamentos PRISMA, en las bases de datos Pubmed, Wiley, Scopus. La búsqueda incluyó estudios publicados entre 2010 - 2020 en inglés, realizados en humanos, en pacientes bajo terapia con ACOD sometidos a exodoncia y que evalúan la incidencia de hemorragia en este procedimiento. Se excluyeron estudios que involucran pacientes que reciben otros tratamientos antitrombótico concomitante, o procedimientos distintos a la exodoncia. La calidad de los estudios seleccionados fue evaluada de acuerdo con la clasificación del Centro Oxford de Medicina Basada en la Evidencia. Luego de la búsqueda, en base a criterios de inclusión/exclusión, 34 artículos fueron analizados a texto completo. Trece artículos relevantes fueron seleccionados. Once participaron en la revisión final, contando con ocho estudios de cohorte, dos casos-controles y uno serie de casos. Los estudios evidencian que no es necesario suspender la terapia con ACOD en pacientes sometidos a exodoncia, se sugiere que el momento de baja concentración farmacológica puede ser utilizado a favor del tratante. Sin embargo, existe una gran diversidad de protocolos y medidas aplicadas entre estudios, por lo que es necesario realizar estudios clínicos aleatorizados controlados, para determinar un protocolo estándar en el manejo odontológico de estos pacientes.

The use of Direct Acting Oral Anticoagulants (ACOD) has increased considerably in recent times. In dental procedures, such as tooth extraction, optimal management of hemostasis in patients treated with ACOD is crucial to balance the risk of bleeding and thromboembolism. There is still no consensus on the protocol to be applied in patients with ACOD in dental extraction. The aim was to evaluate the need to suspend or continue treatment with ACOD in patients submitted to dental extraction in relation to the incidence of bleeding episodes and the protocols used. A systematic review was carried out based on the PRISMA estates, in the Pubmed, Wiley, Scopus databases. The search included studies published between 2010-2020 in English conducted in humans, in patients under therapy with ACOD submitted to dental extraction and that evaluate the incidence of bleeding in this procedure. Studies involving patients receiving other concomitant antithrombotic treatments or procedures other than dental extraction were excluded. The quality of the selected studies was evaluated according to the Oxford Center for Evidence-based Medicine classification. After the search, based on inclusion/ exclusion criteria, 34 articles were analyzed in full text. 13 relevant articles were selected. 11 participated in the final review, including 8 cohort studies, 2 case-controls and 1 case series. Studies show that it is not necessary to suspend therapy with ACOD in patients who have undergone dental extraction, it is suggested that the moment of low pharmacological concentration can be used in favor of the treatment. However, there is a great diversity of protocols and measures applied between studies, so it is necessary to carry out randomized controlled clinical studies to determine a standard protocol in the dental management of these patients.

Mecanismos de acción de agentes propuestos para el tratamiento farmacológico específico de la infección por SARS-CoV-2 / Mechanisms of action of proposed agents for the specific pharmacological treatment of SARS-CoV-2 infection

Resumen Desde la notificación de la pandemia por SARS-CoV-2, agente patógeno responsable del COVID-19, muchos de los tratamientos dirigidos a su manejo han estado sometidos a estudios de manera constante, con el fin de comprobar su eficacia y seguridad. El conocimiento de su virología y etiopatogenia posibilitaría objetivar los pasos moleculares específicos que puedan ser blancos terapéuticos de variados fármacos actualmente disponibles. Esta experiencia proviene principalmente de las infecciones por SARS-CoV y MERS-CoV, con resultados variados 'in vitro' en el SARS-CoV-2, sin evidencia clínica que demuestre efectividad y seguridad de dichos tratamientos. A la fecha, no se ha podido concretar con claridad un esquema de tratamiento específico, debido a que la evidencia surgida ha puesto en jaque cada uno de los fármacos propuestos. Esto ha motivado a continuar en la búsqueda de una estrategia efectiva que permita manejar esta pandemia con la seguridad y eficacia necesaria para que el beneficio terapéutico esté por sobre los posibles efectos adversos que estos esquemas farmacológicos pudiesen presentar. La siguiente revisión pretende mostrar la evidencia disponible a la fecha, definiendo la actividad de cada fármaco en función de su mecanismo de acción.

Since the beginning of the pandemic by SARS-CoV-2, the pathogen responsible for COVID-19, many of the therapeutic options for its management have been under constant revision, in order to verify their safety and efficiency. Knowledge of the viral structure and pathogenesis make it possible to determine the molecular pathways that may be targeted with current available drugs. The experience with these drugs comes mainly from infections caused by SARS-CoV and MERS-CoV, in vitro studies with SARS-CoV-2 that yield variable results, and clinical experience that does not ensure effectiveness and safety of such drugs. To date, it has not been possible to elucidate a specific treatment scheme, because of the constant release of evidence that challenges the usefulness of the proposed drugs. This has motived us to continue seeking for an effective strategy that allows to manage this pandemic in a safe and efficient manner, so that therapeutic benefit surpasses the related adverse drug reactions that can occur. The following review aims to showcase the evidence available to date by defining the activity of each drug based on its mechanism of action.

Anticoagulantes, Antiplaquetarios y sus implicaciones en cirugía: una revisión de la literatura / Anticoagulants, Anti-platelets, and their implications in Surgery: A Literature review

All health care providers should be aware of the impact of bleeding disorders on their patients during any surgical procedures. The knowledge of the mechanisms of hemostasis and optimized management are very important. Initial recognition of a bleeding disorder, in such patients with a systemic pathologic process, may occur in surgical practice. The surgical treatment of those patients might be complicated during the surgery due to the use of anticoagulant and/or antiplatelet medications raises a challenge in the daily practice of surgical professionals. Adequate hemostasis is critical for the success of any surgical procedure because bleeding problems can give rise to complications associated with important morbidity-mortality. Besides, prophylactic, restorative, and surgical care of patients with any bleeding disorders is handled skillfully by practitioners who are well educated regarding the pathology, complications which could arise, and surgical options associated with these conditions. The purpose of this paper is to review common bleeding disorders and their effects on the surgical aspect. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from surgery.

Proposal for the management of COVID-19-associated coagulopathy in children / Propuesta para el manejo de la coagulopatía asociada a COVID-19 en niños

Abstract SARS-CoV-2 infection (COVID-19) has become a pandemic with a high case fatality rate that mainly affects adults. Most severely ill adult patients develop a coagulopathy that was not described until recently, and which is currently considered a main cause of death. Everything indicates that a similar phenomenon also occurs in children with COVID-19. Anticoagulant treatment has become one of the therapeutic foundations for this infection; however, its implementation in children can be difficult since, until recently, it was not considered in the pediatric population. Evidence regarding the use of anticoagulants in COVID-19 is rapidly generated, changes constantly, it is often difficult to interpret, and can be contradictory. After an extensive review of the published literature, a proposal was generated that offers suggestions for anticoagulant treatment, considering available resources in Mexico.

Resumen La infección por SARS-CoV-2 (COVID-19) se ha constituido en una pandemia con alto índice de letalidad que afecta principalmente a los adultos. La mayor parte de los pacientes adultos graves desarrolla una coagulopatía que no estaba descrita, la cual actualmente se considera la principal causa de muerte. Todo indica que un fenómeno parecido ocurre también en el niño con COVID-19. El tratamiento anticoagulante se ha convertido en uno de los fundamentos terapéuticos de esta infección; sin embargo, su establecimiento en el niño puede ser difícil ya que, hasta hace poco, no estaba considerado en la población pediátrica. La evidencia respecto al uso de anticoagulantes en COVID-19 se genera con rapidez, cambia constantemente, con frecuencia es difícil de interpretar y puede ser contradictoria. Después de una extensa revisión de la literatura publicada, se generó una propuesta que ofrece sugerencias para el tratamiento anticoagulante en la que se consideran los recursos disponibles en México.

SBA 2020: Regional anesthesia guideline for using anticoagulants update / SBA 2020: Atualização na diretriz da anestesia regional em uso de anticoagulantes

Abstract The development of protocols to prevent perioperative Venous Thromboembolism (VTE) and the introduction of increasingly potent antithrombotic drugs have resulted in concerns of increased risk of neuraxial bleeding. Since the Brazilian Society of Anesthesiology 2014 guideline, new oral anticoagulant drugs were approved by international regulating agencies, and by ANVISA. Societies and organizations that try to approach concerns through guidelines have presented conflicting perioperative management recommendations. As a response to these issues and to the need for a more rational approach, managements were updated in the present narrative review, and guideline statements made. They were projected to encourage safe and quality patient care, but cannot assure specific results. Like any clinical guide recommendation, they are subject to review as knowledge grows, on specific complications, for example. The objective was to assess safety aspects of regional analgesia and anesthesia in patients using antithrombotic drugs, such as: possible technique-associated complications; spinal hematoma-associated risk factors, prevention strategies, diagnosis and treatment; safe interval for discontinuing and reinitiating medication after regional blockade.

Resumo Os padrões evolutivos para a prevenção do tromboembolismo venoso perioperatório e a introdução de medicações antitrombóticas cada vez mais potentes resultaram em preocupações com o aumento do risco de sangramento neuroaxial. Após o consenso da Sociedade Brasileira de Anestesiologia em 2014, novos medicamentos anticoagulantes orais foram aprovados pelas instituições reguladoras internacionais, assim como pela ANVISA. As sociedades que buscam abordar o manejo perioperatório desses fármacos apresentam recomendações conflitantes. Em resposta a essas questões e à necessidade de uma abordagem mais racional, as condutas foram atualizadas nesta revisão narrativa e feitas declarações de consenso. Elas foram projetadas para encorajar a assistência ao paciente de forma segura e de qualidade, mas não podem garantir um resultado específico. Tal como acontece com qualquer recomendação de orientação clínica, estas estão sujeitas a revisão com o conhecimento de avanços específicos de complicações. O objetivo foi avaliar aspectos da segurança em anestesia e analgesia regional em pacientes em uso de medicações antitrombóticas, tais como: possíveis complicações decorrentes da técnica; fatores de risco associados ao hematoma espinhal, estratégias de prevenção, diagnóstico e tratamento; intervalo seguro para suspensão e reinício da medicação após o bloqueio regional.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Warfarin drug interaction with vitamin K and other foodstuffs / Interacción de la droga warfarina con la vitamina K y otros productos alimenticios

Vitamin K is found in higher concentrations in dark green plant and in vegetable oils. The adequate intake of vitamin K is 90 and 120ug/day for adult elderly men and women, respectively. The main function of vitamin K is to act as an enzymatic cofactor for hepatic prothrombin synthesis, blood coagulation factors, and anticoagulant proteins. Prominent among the many available anticoagulants is warfarin, an antagonist of vitamin K, which exerts its anticoagulant effects by inhibiting the synthesis of vitamin K1 and vitamin KH2. From the beginning of the therapy it is necessary that the patients carry out the monitoring through the prothrombin time and the international normalized ratio. However, it is known that very low intake and/or fluctuations in vitamin K intake are as harmful as high consumption. In addition, other foods can interact with warfarin, despite their content of vitamin K. The aim of this study was to gather information on the drug interaction of warfarin with vitamin K and with dietary supplements and other foods.

La vitamina K se encuentra en concentraciones más altas en plantas de color verde oscuro y en aceites vegetales. La ingesta adecuada de vitamina K es de 90 y 120 ug/día para hombres y mujeres adultos mayores, respectivamente. La función principal de la vitamina K es actuar como un cofactor enzimático para la síntesis de protrombina hepática, factores de coagulación de la sangre y proteínas anticoagulantes. Entre los muchos anticoagulantes disponibles destaca la warfarina, un antagonista de la vitamina K, que ejerce sus efectos anticoagulantes al inhibir la síntesis de la vitamina K1 y la vitamina KH2. Desde el inicio de la terapia, es necesario que los pacientes realicen el monitoreo a través del tiempo de protrombina y la proporción normalizada internacional. Sin embargo, se sabe que una ingesta muy baja y/o fluctuaciones en la ingesta de vitamina K son tan dañinas como un consumo alto. Además, otros alimentos pueden interactuar con la warfarina, a pesar de su contenido de vitamina K. El objetivo de este estudio fue recopilar información sobre la interacción de los medicamentos de la warfarina con la vitamina K y con los suplementos dietéticos y otros alimentos.