Prophylactic low-molecular-weight heparin in women with thrombophilia undergoing in vitro fertilization.

OBJECTIVE: To verify whether low-molecular-weight heparin (LMWH) could increase pregnancy rates and/or decrease abortion rates in women with thrombophilia undergoing assisted reproduction cycles. METHODS: Cross-sectional study with patients undergoing in vitro fertilization (IVF) (N = 104). Women without thrombophilia (control group, n = 20), women with thrombophilia who did not receive LMWH (untreated group, n = 30), and women with thrombophilia, treated with daily enoxaparin from the day of embryo transfer until week 36 of gestation (treated group, n = 54). All women underwent controlled ovarian hyperstimulation. IVF was performed by intracytoplasmic sperm injection, and embryos were transferred on day 3. Pregnancy was detected by ß-human chorionic gonadotropin (biochemical pregnancy) and fetal heartbeat at week 5 to 6. Ongoing pregnancy was determined by ultrasound on week 12. RESULTS: Patients in the untreated thrombophilia group presented with significantly lower ongoing pregnancy rates and live birth rates and significantly higher early pregnancy loss and abortion rates when compared with the control and the treated thrombophilia groups. CONCLUSIONS: In women with diagnosed coagulation disorders, use of LMWH is important to avoid miscarriages.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity.

OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (ß=-0.081, p=0.014), resistance index of the umbilical artery (ß=0.601, p=0.039), and D-dimer (ß=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Coronavirus disease 2019-induced hypercoagulability and its clinical implications.

Coronavirus disease 2019 is the disease produced by severe acute respiratory syndrome-coronavirus-2, which is introduced into the host's cell thanks to the angiotensin-converting enzyme 2 receptor. Once there, it uses the cell's machinery to multiply itself. In this process, it generates an immune response that stimulates the lymphocytes to produce cytokines and reactive oxygen species that begin to deteriorate the endothelial cell. Complement activation, through the complement attack complex and C5a, contributes to this endothelial damage. The different mediators further promote the expression of adhesion molecules on the endothelial surface, which encourages all blood cells to adhere to the endothelial surface to form small conglomerates, called clots, which obstruct the lumen of the small blood vessels. Furthermore, the mediators of clot lysis are inhibited. All this promotes a prothrombotic environment within the pulmonary capillaries that is reflected in the elevation of D-dimer. The only solution for this cascade of events seems to be the implementation of an effective anticoagulation protocol that early counteracts the changes induced by thrombi in the pulmonary circulation and reflected in the functioning of the right ventricle.

Enoxaparina 60 mg/0, 6 mL injetável para a prevenção de tromboembolismo venoso em gestantes com trombofilia / Enoxaparin 60 mg/0. 6 mL injectable for the prevention of venous thromboembolism in pregnant women with thrombophilia

CONTEXTO: O tromboembolismo venoso (TEV) associado à gravidez, incluindo trombose venosa profunda (TVP) e embolia pulmonar (EP), embora incomum, continua sendo causa importante de morbimortalidade. Por ser uma condição próinflamatória com ativação de células endoteliais, as gestantes apresentam um risco maior de TEV quando comparado com mulheres não grávidas. Mulheres com trombofilia e aquelas que se submetem à cesariana representam a maioria das pacientes com TEV pós-parto. Atualmente, o Brasil possui um Protocolo Clínico e Diretrizes Terapêuticas (PCDT) de Profilaxia do Tromboembolismo Venoso em Gestantes com Trombofilia. O PCDT foi publicado por meio da Portaria Conjunta SAES-SCTIE nº 04, de 12 de fevereiro de 2020 e preconiza o uso do medicamento enoxaparina para prevenção e tratamento do tromboembolismo venoso em gestantes com trombofilia. Entretanto, a apresentação de 60 mg/0,6 mL de enoxaparina, necessária para uma dose precisa em grávidas ou puérperas com trombofilia com massa corporal acima de 90 kg com indicação de anticoagulação profilática ou em grávidas ou puérperas com trombofilia e indicação de esquema de anticoagulação plena, independentemente do peso corporal, atualmente não está disponível no SUS. TECNOLOGIA: Enoxaparina sódica 60 mg/0,6 mL injetável. PERGUNTA: A enoxaparina 60 mg/0,6mL é eficaz, efetiva e segura em grávidas ou puérperas com trombofilia com massa corporal acima de 90 kg que estiverem em tratamento com esquema de anticoagulação profilática ou em gestantes com indicação esquema de anticoagulação plena, independentemente do peso corporal? EVIDÊNCIAS CLÍNICAS: Foram incluídos 4 estudos descritos em 5 referências, sendo 02 ensaios clínicos randomizados (ECR) e dois estudos observacionais do tipo coorte retrospectiva. Os estudos apontam que não há diferenças significativas para os desfechos de eficácia, efetividade e segurança entre a dose mínima e o ajuste de dose de enoxaparina na Prevenção de Tromboembolismo Venoso em Gestantes com Trombofilia. Para o desfecho mais relevante que corresponde ao número de nascidos vivos por gestação, a meta-análise incluiu 165 gestantes recebendo enoxaparina com dose ajustada e 155 gestantes recebendo 40 mg/dia de enoxaparina em dose fixa. O resultado agrupado dos dois ECRs gerou um RR de 0,95 sem diferença estatisticamente significante entre os grupos no modelo de efeitos randômicos, (IC95% = 0,86 ­ 1,04; I 2 = 0%; p = 0,55). Nos efeitos indesejáveis da tecnologia, ambas as doses de enoxaparina indicam ser seguras e bem toleradas (Anexo 1). ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foi adotado um horizonte temporal de cinco anos (2021 a 2025). No cenário mais conservador, a análise de impacto orçamentário evidenciou uma economia de R$ 55.369.020,00 diante da incorporação da enoxaparina 60 mg/0,6 mL no SUS (Anexo 2). MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Não foram detectadas tecnologias para compor o esquema terapêutico de prevenção de tromboembolismo venoso em gestantes com trombofilia. No Brasil, a enoxaparina não está sob proteção patentária. CONSIDERAÇÕES FINAIS: Considerou-se que a enoxaparina 60 mg/0,6 mL mostra-se como uma alternativa segura quando comparada à dose mínima de 40 mg/0,4 mL. Ademais, a incorporação da enoxaparina 60 mg/0,6 mL pode levar à economia de R$ 55.369.020,00 ao longo de cinco anos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da Conitec, em sua 96ª Reunião Ordinária, no dia 07 de abril de 2021, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à incorporação da enoxaparina 60 mg/0,6 mL injetável para a prevenção de tromboembolismo venoso em gestantes com trombofilia no SUS. Os membros da Conitec consideraram que a incorporação desta nova apresentação de enoxaparina é necessária para a prevenção de tromboembolismo venoso em gestantes com sobrepeso ou com indicação de anticoagulação plena. Além disso, considerou-se que essa incorporação potencialmente irá representar economia para o Sistema Único de Saúde. CONSULTA PÚBLICA: Foram recebidas 16 contribuições, sendo 8 técnico-científicas e 8 sobre experiência ou opinião. A grande maioria destas concordou da recomendação inicial da Conitec. Ao final, o Plenário da Conitec entendeu que não foram apresentadas novas evidências que mudassem seu entendimento sobre o tema, fazendo com que sua recomendação preliminar fosse mantida. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 98ª Reunião Ordinária, no dia 09 de junho de 2021, deliberou por unanimidade recomendar a incorporação da enoxaparina 60 mg/0,6 mL injetável para a prevenção de tromboembolismo venoso em gestantes com trombofilia. Assim, foi assinado o Registro de Deliberação nº 622/2021. DECISÃO: Incorporar a enoxaparina 60 mg/0,6 mL injetável para a prevenção de tromboembolismo venoso em gestantes com trombofilia, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 35, publicada no Diário Oficial da União nº 127, seção 1, página 143, em 08 de julho de 2021.

An evaluation of ticagrelor for the treatment of sickle cell anemia.

INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.

Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review.

BACKGROUND: The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. CASE PRESENTATION: A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1­Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. CONCLUSION: Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.

Anticoagulação e prevenção de morbidade obstétrica em trombofilias hereditárias: mito ou verdade? / Anticoagulation and prevention of obstetric morbidity in hereditary thrombophilia: myth or truth?

Tem sido observado, corriqueiramente, o uso indiscriminado de anticoagulantes durante a gravidez com a finalidade de evitar perdas gestacionais. A eficácia do uso de anticoagulantes na prevenção de perdas, precoces e tardias, tem sido questionada, levando-se em consideração os impactos econômicos, sociais e psicológicos gerados nas famílias a partir da indicação da utilização dessa terapia. Dada a relevância do tema, realizou-se uma revisão da literatura nos bancos de dados PubMed, Cochrane Library e Medline com a finalidade de avaliar evidências científicas do uso e da eficácia de anticoagulação na gravidez. Na literatura revisada, não foi possível sustentar a hipótese de que a anticoagulação é capaz de intervir ativamente no sucesso do curso da gravidez. Conclui-se, portanto, que mais estudos devem ser realizados a fim de determinar intervenções eficazes ao casal, preservar a saúde do concepto e minimizar o impacto econômico, social e psicológico da utilização de anticoagulantes durante a gravidez.(AU)

In medical practice, the anticoagulants indiscriminate use during pregnancy has been commonly observed to prevent future pregnancy losses. The effectiveness of using anticoagulants in preventing losses, early and late, has been questioned taking into account the economic, social and psychological impacts generated on families from the indication of the use of such drugs. Given the relevance of the topic, a literature review was carried out in the PubMed, Cochrane Library and Medline databases in order to assess scientific evidence on the anticoagulation efficacy use in pregnancy. It was not possible to support the hypothesis that anticoagulation is able to actively intervene in the success of the course of pregnancy. It is concluded, therefore, that more studies should be carried out in order to determine effective interventions for the couple, preserve the health of the fetus and minimize the economic, social and psychological impact of the anticoagulants use during pregnancy.(AU)

Consensus on the investigation of thrombophilia in women and clinical management.

OBJECTIVE: To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. METHODOLOGY: A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. CONCLUSION: The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

Statin Therapy to Revert Hypercoagulability and Prevent Venous Thromboembolism: A Narrative Review.

Venous thromboembolism (VTE) causes a major disease burden worldwide, so that effective preventive measures are warranted. Although oral anticoagulation is effective in preventing VTE episodes, bleeding complications are a major concern that may lead to treatment avoidance. Statin therapy, which is widely used for prevention of arterial cardiovascular disease, is a promising alternative treatment for VTE prophylaxis, as the drug may affect hemostasis without increasing the risk of bleeding. In the past years, clinical studies have suggested that statins can interfere with blood coagulation and, in turn, reduce the risk of VTE. These effects, however, are still regarded with skepticism, as the underlying mechanisms by which statins may affect hemostasis in humans are not clear and data showing that statin therapy reduces VTE risk mostly came from observational studies, while only one randomized trial was conducted to evaluate this issue. In this review, the authors summarize the currently available evidence regarding the effect of statin therapy on coagulation and on VTE prevention. Recent randomized data showed that statin therapy, in particular rosuvastatin, leads to decreased levels of coagulation factors in patients with prior VTE. This evidence provides a reasonable basis for interventional studies necessary to establish the efficacy of statins on reducing the risk of incident and recurrent VTE.

Consensus on the investigation of thrombophilia in women and clinical management / Consenso sobre a investigação de trombofilia em mulheres e manejo clínico

ABSTRACT Objective To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. Methodology A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. Conclusion The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

RESUMO Objetivo Padronizar a investigação e o manejo clínico de mulheres com anormalidades clínicas e exames laboratoriais sugestivos de trombofilia, para melhorar a abordagem antitrombótica e otimizar a indicação de exames laboratoriais. Metodologia Foi conduzida discussão incluindo 107 médicos (ginecologistas/obstetras, hematologistas e cirurgiões vasculares) participantes de um fórum realizado no Hospital Israelita Albert Einstein, em São Paulo (SP). Como critério mínimo, estabeleceu-se concordância de 80% em votação para cada recomendação de conduta registrada em documento como diretrizes finais. Os casos em que a concordância esteve abaixo de 80% foram rediscutidos, para definir consenso na conduta. Conclusão A padronização e o estabelecimento de consenso institucional, com sugestões para abordagem clínica, contribui para melhorar o manejo do grupo a ser avaliado e minimizar os riscos de intercorrências. Este foi o primeiro consenso nacional sobre investigação de trombofilia em mulheres.

Diagnóstico y tratamiento de las trombofilias en edad fértil / Diagnosis and treatment of thrombophilias of childbearing age

INTRODUCCIÓN: El embarazo se caracteriza por ser un estado protrombótico, con aumento del potencial procoagulante, disminución de la actividad anticoagulante y de la actividad fibrinolítica. A esto se le suma la estasis venosa de miembros inferiores por compresión del útero sobre los grandes vasos venosos pelvianos, aumento de la capacitancia venosa, aumento de la resistencia a la insulina y del perfil lipídico protrombótico. Existe asociación entre la trombofilia y la ocurrencia de trombosis venosa profunda. Adicionalmente, las trombofilias tanto hereditarias como adquiridas se han asociado a resultados adversos en los embarazos, tales como abortos espontáneos, muerte fetal tardía, preeclampsia, restricción en el crecimiento intrauterino (RCIU) y desprendimento placentario. ESTRATEGIA DE BÚSQUEDA: Se realizó una búsqueda no sistemática de la evidencia para responder a los interrogantes clínicos. Los sitios de búsqueda incluyeron bases de datos electrónicas (PUBMED, Cochrane library, TripDatabase, Epistemonikos), Agencias de Evaluación de Tecnologías Sanitarias, organismos elaboradores de Guías de Práctica Clínica y sumários electrónicos de alta calidad. Se recuperó adicionalmente información relevante proveniente de las citas de los trabajos encontrados mediante la estrategia inicial. Se utilizaron como criterios de inclusión estudios de investigación secundarios (Guías de Práctica Clínica y Consensos de Sociedades Científicas, Revisiones Sistemáticas, Informes de Evaluación de Tecnologías Sanitarias) que analizaran información sobre métodos diagnósticos y/o tratamiento de las trombofilias; complicaciones obstétricas y maternas tanto de la patología como de su tratamiento. RESULTADOS: Se seleccionaron 10 estudios considerados pertinentes. CONCLUSIONES: Existe evidencia escasa sobre cuatro puntos relevantes: si la presencia de trombofilias hereditarias y/o adquiridas se asocia con resultados adversos en los embarazos, qué subgrupo de pacientes es el que se puede beneficiar con la realización de pruebas de diagnóstico, si el tratamiento anticoagulante que se indica a partir de este diagnóstico mejora los resultados en salud de los embarazos; y si el tratamiento anticoagulante es razonablemente seguro para su indicación en las mujeres que reciban el diagnóstico de trombofilias. Estas preguntas no quedan respondidas con suficiente confianza a partir de este informe ultrarrápido, en donde no fue posible realizar una búsqueda exhaustiva ni sistemática de evidencia. Por otro lado, la calidad de la evidencia no fue evaluada de manera formal debido a la necesidad de una respuesta en un lapso breve de tiempo. Sin embargo se puede afirmar que, por el diseño de los estudios incluidos, es para la mayoría de los casos, baja. El punto en el que más coincidencia se encuentra es que las pruebas diagnósticas deben ser limitadas a un grupo seleccionado de pacientes (historia personal de aborto recurrente, de eventos tromboembólicos, o historia familiar de primer grado), y no deben ser solicitadas de rutina a mujeres en edad fértil, ni a mujeres con un antecedente de aborto, ni a mujeres que tengan hasta dos intentos de fertilización asistida fallidos. Y aún en estos grupos seleccionados el tratamiento posterior con anticoagulación se encuentra cuestionado. En caso de trombofilias hereditarias, el tratamiento con heparina de bajo peso molecular no mostró mejorar la tasa de nacidos vivos en comparación com pacientes que no recibieron HBPM. En cambio en el caso de Sindrome antifosfolipídico los estudios sí mostraron mejores resultados en cuanto a tasa de nacidos vivos em mujeres que recibieron HBPM en comparación con las que no lo recibieron. Todos los estudios en los que se basa este efecto fueron de bajo número de participantes, por los que estos datos deben interpretarse con cautela. Sobre cuáles son los estudios que deberían solicitarse, no se observa concordancia entre los hallados en las recomendaciones nacionales e internacionales y los propuestos en el artículo 6 del proyecto de ley recibido. Se efectuó una búsqueda sobre cada uno de los métodos mencionados en el artículo 6. Para ninguno de ellos se encontró recomendación a favor de incluirlos. La mayoría de los trabajos incluidos coincide en recomendar como pruebas diagnósticas al factor V de Leiden y a la mutación del gen de la protrombina em caso de trombofilias hereditarias; y a los anticuerpos antifosfolipídicos en el caso de trombofilias adquiridas. Debido a la relevancia de este tema en relación a su impacto en el sistema de salud, a que existen estudios heterogéneos con resultados contradictorios, y a que la evidencia es de calidad incierta, se recomienda complementar esta revisión rápida con la elaboración de Recomendaciones basadas en evidencia, a través de um Informe de Evaluación de Tecnología Sanitaria y/o una Guía de Práctica Clínica, que incluyan la valoración de la calidad de la evidencia existente y sínteses cuantitativa de los datos hallados.

Enoxaparina para gestantes com trombofilia / Enoxaparin for pregnant women with thrombophilia

CONTEXTO: Gestantes com trombofilia com ou sem causas hereditárias associadas. TECNOLOGIA: Enoxaparina sódica. INDICAÇÃO: Gestantes e puérperas com trombofilia. PERGUNTA: A enoxaparina é mais eficaz, efetiva e segura em comparação ao ácido acetilsalicílico (AAS) em mulheres grávidas com trombofilia? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos uma revisão sistemática (RS), dois Ensaios Clínicos Randomizados (ECR) e duas coortes (ambas não concorrentes). A RS de De Jong et al., 2013 (alta qualidade metodológica) demonstrou que, nas gestantes com história de aborto, houve um número significativamente maior de nascidos vivos no grupo tratado com enoxaparina, quando comparado ao grupo do AAS. O ECR de Elmahashi et al., 2014 (moderada qualidade metodológica) relatou superioridade da enoxaparina associada ao AAS, quando comparado ao AAS isolado para os desfechos número de abortos e número de nascidos vivos. O ECR de Gris et al., 2004 (moderada qualidade metodológica) relatou que o uso da enoxaparina em gestantes resultou em um número maior de nascidos vivos quando comparado ao AAS, sendo a diferença estatisticamente significante. A coorte conduzida por Bar et al., 2000 (baixa qualidade metodológica) constatou que, quanto ao potencial teratogênico, não houveram diferenças estatisticamente significantes entre enoxaparina e AAS. A coorte de Merviel et al., 2017 (baixa qualidade metodológica) mostrou superioridade estatisticamente significante da enoxaparina associada ao AAS para os desfechos número de nascidos vivos e taxa de aborto no 1° trimestre de gestação, quando comparado ao AAS isolado. AVALIAÇÃO ECONÔMICA: Foi conduzida avaliação econômica do tipo árvore de decisão, a perspectiva adotada foi a do SUS e o horizonte temporal utilizado foi o de uma gestação (40 semanas ­ 280 dias). O desfecho de efetividade considerado foi o sucesso da gestação, com o nascimento a termo ou pré-termo. Foram também considerados os eventos aborto e morte intrauterina. A análise de custo-efetividade mostrou que o uso da enoxaparina em comparação com AAS custaria R$3.466,42 a mais para o tratamento de cada gestante com trombofilia, sendo a razão de custo efetividade incremental de R$11.074,81 por nascido vivo. A estratégia AAS + Enoxaparina foi dominada, pois apresentou maior custo e menor efetividade que a Enoxaparina isoladamente. A análise de sensibilidade mostrou que a variável que mais altera o resultado final é o custo da enoxaparina. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Realizou-se análise de impacto orçamentário em um horizonte temporal de 5 anos. Assumiu-se um market share inicial de 20% para a enoxaparina, com incrementos anuais no mesmo valor, chegando a 100% no quinto ano. A estimativa de impacto orçamentário decorrente da incorporação de enoxaparina pode variar entre R$ 7.839.022,67 a R$ 17.739.592,58 milhões de reais em 5 anos. CONSIDERAÇÕES FINAIS: As evidências elencadas nesse relatório demonstram superioridade da enoxaparina em relação ao AAS para o maior número de nascidos vivos, e, consequentemente menor taxa de abortos, entre as gestantes trombofílicas. No que diz respeito aos eventos adversos, não se observa diferença entre as alternativas. Destaca-se que a bula da enoxaparina não possui indicação para o uso em mulheres gestantes e apresenta categoria de risco C na gravidez. O uso off-label da enoxaparina para profilaxia do TEV em gestantes, entretanto, já está consolidado na prática médica. CONSULTA PÚBLICA: O Relatório de Recomendação da CONITEC "Enoxaparina para gestantes com trombofilia" foi disponibilizado por meio da Consulta Pública nº 59/2017 entre os dias 25/10/2017 e 13/11/2017. Foram recebidas 83 contribuições, sendo 4 contribuições técnicocientíficas e 79 de experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Do total de contribuições, 96,4% (n = 80) concordaram totalmente, 2,4% (n = 2) concordaram parcialmente e 1,2% (n = 1) discordaram parcialmente da recomendação preliminar da CONITEC. Nenhuma sugestão ou oposição à incorporação da Enoxaparina foi relatada, a única contribuição parcialmente discordante referia-se a burocracia envolvida no acesso ao medicamento. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 62ª reunião ordinária, no dia 07 de dezembro de 2017, deliberaram, por unanimidade, recomendar a incorporação da enoxaparina sódica 40 mg/0,4 mL para o tratamento de gestantes com trombofilia. Foi assinado o Registro de Deliberação nº 316/2017. DECISÃO: Incorporar a enoxaparina sódica 40 mg/ 0,4 mL para o tratamento de gestantes com trombofilia no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria nº 10, publicada no DOU nº 18, do dia 25 de janeiro de 2018, seção 1, pág. 124.

[Thrombotic and haemorrhagic complications in patients with cerebral aneurysms treated by endovascular approach and their association with the use of antiplatelet agents: Descriptive evaluation]. / Complicaciones trombóticas y hemorrágicas en pacientes con aneurismas cerebrales tratados por vía endovascular y su relación con el uso de antiagregantes plaquetarios: evaluación descriptiva.

OBJECTIVE: The protocol for optimal antiplatelet therapy to prevent thrombotic complications following brain aneurysm embolisation is not clear. Our objective is to describe the characteristics of patients presenting with thrombotic or haemorrhagic complications secondary to endovascular treatment. METHODS: A cross sectional descriptive study was performed, which included all patients that required endovascular treatment for brain aneurysm at San Ignacio University Hospital from November 2007 to January 2016. Thrombotic and haemorrhagic complications over six months of follow-up were assessed, considering the premedication regimen with antiplatelet agents, location, size of the aneurysm and embolisation technique performed. RESULTS: 122 patients were evaluated, on whom 130 procedures were performed for endovascular treatment of brain aneurysms. Thrombotic complications were more frequent in patients who did not receive premedication (25%) compared to those who did receive an antiplatelet treatment regimen (standard dose 3.87% or loading dose 8.70%), and this difference was statistically significant (P=.043). CONCLUSIONS: Thromboembolic events are the most common complication of brain aneurysm embolisation. Both our study and the literature suggest that the use of dual antiplatelet therapy with aspirin and clopidogrel lowers the rate of symptomatic thromboembolic complications, regardless of the administration protocol.

Surgical Interventions for Organ and Limb Ischemia Associated With Primary and Secondary Antiphospholipid Antibody Syndrome With Arterial Involvement.

OBJECTIVE: The association of antiphospholipid antibody syndrome (APS) and hypercoagulability is well known. Arterial compromise leading to ischemia of organs and/or limbs in patients with APS is uncommon, frequently unrecognized, and rarely described. We evaluated our institutional experience. METHODS: Retrospective review was conducted. From August 2007 to September 2016, 807 patients with diagnosis of APS were managed in our Institution. Patients with primary and secondary APS who required interventions were examined. Demographics, comorbidities, manifestations, procedures, complications, and other factors affecting outcomes were recorded. RESULTS: Fourteen patients (mean age 35 years old, standard deviation ±14) were evaluated and treated by our service. Six (43%) of them had primary APS and 8 (57%) had secondary APS; 11 (79%) were female. Two (14%) experienced distal aorta and iliac arteries involvement, 3 (21%) visceral vessels disease, 2 (14%) in upper and 7 (50%) in the lower extremity vasculatures. Thirteen (93%) patients underwent direct open revascularization and 1 with hand ischemia (Raynaud disease) underwent sympathectomy. During the mean follow-up period of 48 months, reinterventions included a revision of the proximal anastomosis of an aortobifemoral bypass graft, 1 (7%) abdominal exploration for bleeding, 1 (7%) graft thrombectomy, and 4 (29%) amputations (2 below the knee, 1 above the knee, and 1 transmetatarsal). One (7%) death occurred secondary to sepsis in a patient who had acute mesenteric ischemia. Significant differences in clinical manifestations and outcomes were not observed among patients with primary and secondary APS. All patients remained on systemic anticoagulation. CONCLUSION: APS is a prothrombotic disorder that may lead to arterial involvement with less frequency than the venous circulation but has significant morbidity and limb loss rate. Arterial reconstruction seems feasible in an attempt to salvage organs and limbs; however, research is necessary to establish the optimal anticoagulation regime and long-term management following surgical interventions.

Early postoperative bridging anticoagulation after mechanical heart valve replacement: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of studies evaluating anticoagulation during the early postoperative period following mechanical heart valve implantation. METHODS: Five literature databases were searched to assess the rates of bleeding and thromboembolic events among patients receiving oral anticoagulation (OAC), both with and without bridging anticoagulation therapy with unfractionated heparin (UFH) or subcutaneous low molecular weight heparin (LMWH). The studies' results were pooled via a mixed effects meta-analysis. Heterogeneity (I(2) ) and publication bias were both evaluated. RESULTS: Twenty-three studies including 9534 patients were included. The bleeding rates were 1.8% (95% confidence interval CI 1.0-3.3) in the group receiving OAC, 2.2% (95% CI 0.9-5.3) in the OAC + UFH group, and 5.5% (95% CI 2.9-10.4) in the OAC + LMWH group (P = 0.042). The thromboembolic event rate was 2.1% (95% CI 1.5-2.9) in the group receiving OAC, as compared with 1.1% (95% CI 0.7-1.8) when the bridging therapy groups were combined as follows: OAC + UFH and OAC + LMWH (P = 0.035). Most of the analyses showed moderate heterogeneity and negative test results for publication bias. CONCLUSIONS: Bridging therapy following cardiac valve surgery was associated with a lower thromboembolic event rate, although the difference was small, with considerable overlap of the CIs. Direct comparisons are missing. Bridging therapy with UFH appears to be safe; however, this observation has a risk of bias. Early bridging therapy with LMWH appears to be associated with consistently high bleeding rates across multiple analyses. On the basis of the quality of the included studies, more trials are necessary to establish the clinical relevance of bridging therapy and the safety of LMWH.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

BACKGROUND: Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. METHODS AND RESULTS: Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. CONCLUSIONS: Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients.