COVID-19-associated coagulopathy and acute kidney injury in critically ill patients

ABSTRACT Objective The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. Methods Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. Results Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. Conclusion Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Low platelet reactivity in patients with myocardial infarction treated with aspirin plus ticagrelor

ABSTRACT Objective: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. Methods: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. Results: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). Conclusion: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Consenso Colombiano para la prevención, diagnóstico y manejo de condiciones trombóticas en pacientes adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adult patients with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

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Abstract Recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. In this context, the aim was to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: A rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: Recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Incidence, diagnosis, treatment methods, and outcomes of clinically suspected venous thromboembolic disease in patients with COVID-19 in a quaternary hospital in Brazil / Incidência, diagnóstico, métodos terapêuticos e desfechos de eventos tromboembólicos venosos em pacientes com COVID-19 em um hospital quaternário do Brasil

Abstract Background Prothrombotic states have been associated with viral infections and the novel Sars-COV-2 infection has been associated with elevated D-dimer levels, although no causal relation has been clearly established. Objectives This study presents an epidemiological analysis of manifest VTE episodes in a group of patients hospitalized because of COVID-19. Methods Medical records of patients who presented symptomatic deep vein thrombosis and/or pulmonary embolism in concomitance with confirmed COVID-19 were retrospectively studied. Demographic characteristics, prevalence of VTE, site of occurrence, D-dimer variation over time, management, and outcomes were analyzed. Results During the study period, 484 confirmed cases of COVID-19 were admitted, 64 of which displayed VTE symptoms and 13 of which had confirmed symptomatic VTE(2.68% of total sample and 20.31% of symptomatic cases). Most cases (76.92%) occurred in intensive care. On the day attributed to VTE onset, D-dimer levels were over 3,000 ng/mL in 8 (80%) patients, a significant increase from baseline admission levels (p < 0.05). A significant decrease was also observed in D-dimer values at hospital discharge (p < 0.05). All patients received pharmacological thromboprophylaxis and/or anticoagulation as indicated. Two deaths occurred during the study, both patients with severe comorbidities. At the end of our study protocol, nine patients had been discharged and two remained hospitalized, but had no signs of VTE worsening. Conclusions VTE prevalence in hospitalized COVID-19 patients was 2.7%, and higher in intensive care units. Early institution of prophylaxis and immediate full anticoagulation when VTE is diagnosed should be the goals of those who treat this kind of patient.

Resumo Contexto Os estados pró-trombóticos têm sido associados a infecções virais. A nova infecção pela síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) sabidamente eleva os níveis de D-dímero, embora a relação causal não tenha sido bem estabelecida. Objetivos Este estudo apresenta uma análise epidemiológica de episódios sintomáticos de tromboembolismo em um grupo de pacientes hospitalizados pela doença do novo coronavírus (COVID-19). Métodos Foi realizada uma revisão retrospectiva de prontuários de pacientes internados por COVID-19 que apresentaram trombose venosa profunda e/ou embolia pulmonar sintomáticas. Foram avaliados os dados demográficos, a prevalência de tromboembolismo, a variação do D-dímero ao longo do tempo, o manejo e os desfechos. Resultados Dos 484 casos confirmados de COVID-19 admitidos entre março e julho de 2020, 64 apresentaram sintomas de tromboembolismo, que foram investigados, e 13 tiveram tromboembolismo confirmado (2,68% do total e 20,31% dos sintomáticos). A maioria dos casos ocorreu em regime de terapia intensiva (76,92%). Houve um aumento significativo no número de pacientes com D-dímero acima de 3.000 ng/mL no dia atribuído ao diagnóstico de tromboembolismo com relação aos níveis do momento da admissão (80%, p < 0,05).Uma queda significativa de pacientes nesse limiar também foi observada no momento da alta (p < 0,05). Todos os pacientes receberam tromboprofilaxia ou anticoagulação conforme indicado. Houve dois óbitos na amostra, ambos pacientes com comorbidades severas. Ao fim do protocolo, nove pacientes receberam alta e dois permaneceram hospitalizados, mas sem sinais de piora. Conclusões A prevalência de tromboembolismo em pacientes hospitalizados por COVID-19 foi de 2,7%, sendo mais frequente em regime de terapia intensiva. A instituição precoce de profilaxia e anticoagulação imediata ao diagnóstico é primordial nesse grupo de pacientes.

Consenso colombiano para la prevención, el diagnóstico y el tratamiento de condiciones trombóticas en adultos con COVID-19: aplicando el Marco de la Evidencia a la Decisión (EtD) GRADE / Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introducción estudios recientes han reportado fenómenos trombóticos o coagulopatía en pacientes con COVID-19. Hay posiciones divergentes en cuanto a la prevención, el diagnóstico y el tratamiento de estos fenómenos, y la práctica clínica actual está basada únicamente en deducciones por extensión a partir de estudios retrospectivos, series de casos, estudios observacionales y guías internacionales desarrolladas previas a la pandemia. Objetivo establecer una serie de recomendaciones sobre prevención, diagnóstico y manejo de las complicaciones trombóticas asociadas a COVID-19. Métodos se desarrolló una guía rápida en la que se aplicó el marco de la evidencia a la decisión (EtD) de GRADE y un sistema de participación iterativo, con análisis estadísticos y cualitativos de sus resultados. Resultados se generaron 31 recomendaciones clínicas enfocadas a: a) Pruebas de coagulación en adultos sintomáticos con sospecha de infección o infección confirmada por SARS-CoV-2; b) Tromboprofilaxis en personas adultas con diagnóstico de COVID-19 (escalas de riesgo, tromboprofilaxis de manejo ambulatorio, intrahospitalario y duración de tromboprofilaxis después del egreso de hospitalización), c) Diagnóstico y tratamiento de las complicaciones trombóticas y d) Manejo de personas con indicación previa a usar agentes anticoagulantes. Conclusiones las recomendaciones clínicas de este consenso orientan la toma de decisiones clínicas respecto a prevención, diagnóstico y tratamiento de fenómenos trombóticos en pacientes con COVID-19, y representan un acuerdo que ayudará a disminuir la dispersión en las prácticas clínicas acorde con el desafío que impone la pandemia.

Abstract Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection; b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

A tromboelastometria identifica coagulopatia associada à insuficiência hepática e coagulação intravascular disseminada causadas por febre amarela, orientando a terapia hemostática específica: um relato de caso / Thromboelastometry identifies coagulopathy associated with liver failure and disseminated intravascular coagulation caused by yellow fever, guiding specific hemostatic therapy: a case report

RESUMO Este relato de caso detalha um caso grave de febre amarela complicada por insuficiência hepática e coagulação intravascular disseminada. A tromboelastometria foi capaz de identificar os distúrbios da coagulação e orientar o tratamento hemostático. Relatamos o caso de um homem com 23 anos de idade admitido na unidade de terapia intensiva com quadro com início abrupto de febre e dor muscular generalizada associados a insuficiência hepática e coagulação intravascular disseminada. Os resultados dos exames laboratoriais convencionais revelaram trombocitopenia, enquanto a tromboelastometria sugeriu coagulopatia com discreta hipofibrinogenemia, consumo de fatores de coagulação e, consequentemente, aumento do risco de sangramento. Diferentemente dos exames laboratoriais convencionais, a tromboelastometria identificou o distúrbio de coagulação específico e, assim, orientou o tratamento hemostático. Administraram-se concentrados de fibrinogênio e vitamina K, não sendo necessária a transfusão de qualquer componente do sangue, mesmo na presença de trombocitopenia. A tromboelastometria permitiu a identificação precoce da coagulopatia e ajudou a orientar a terapêutica hemostática. A administração de fármacos hemostáticos, incluindo concentrados de fibrinogênio e vitamina K, melhorou os parâmetros tromboelastométricos, com correção do transtorno da coagulação. Não se realizou transfusão de hemocomponentes, e não ocorreu qualquer sangramento.

Abstract This case report a severe case of yellow fever complicated by liver failure and disseminated intravascular coagulation. Thromboelastometry was capable of identifying clotting disorders and guiding hemostatic therapy. We report the case of a 23-year-old male admitted to the Intensive Care Unit with sudden onset of fever, generalized muscle pain associated with liver failure, and disseminated intravascular coagulation. The results of conventional laboratory tests showed thrombocytopenia, whereas thromboelastometry suggested coagulopathy with slight hypofibrinogenemia, clotting factor consumption, and, consequently, an increased risk of bleeding. Unlike conventional laboratory tests, thromboelastometry identified the specific coagulation disorder and thereby guided hemostatic therapy. Both fibrinogen concentrates and vitamin K were administered, and no blood component transfusion was required, even in the presence of thrombocytopenia. Administration of hemostatic drugs, including fibrinogen concentrate and vitamin K, improved thromboelastometric parameters, correcting the complex coagulation disorder. Blood component transfusion was not performed, and there was no bleeding.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection / Recomendações de suporte intensivo para pacientes graves com infecção suspeita ou confirmada pela COVID-19

ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).

Bleeding management after implementation of the Hemorrhage Code (Code H) at the Hospital Israelita Albert Einstein, São Paulo, Brazil / Manejo de sangramento após implantação do Código Hemorrágico (Código H) no Hospital Israelita Albert Einstein, São Paulo, Brasil

ABSTRACT Objective To describe the implementation of a care protocol based on rapid response teams, for management and resolution of bleeding. Methods A hospital protocol called Hemorrhage Code (Code H) was devised and developed. In a flow line, a multidisciplinary team provides comprehensive, fast and effective care to the patient with a severe hemorrhagic condition. In another flow line, professionals based at the hospital pharmacy focus on identifying patients at risk of bleeding, to avoid this event. Several hospital professionals and sectors were trained, each with specific roles, ensuring full support to the medical and nursing staffs. Results After implementing this protocol, we were able to significantly reduce the number of catastrophic events related to failure in bleeding management. Conclusion Code H is an example of a value-based medicine and precision medicine project by delivering comprehensive and multidisciplinary care, in addition to point-of-care testing introduced in clinical practice, optimizing patient safety and care practices at the hospital. Furthermore, it will be possible to minimize the risk of lawsuits for the hospital and physicians, as well as rationalizing resources with benefits for administrators and payers.

RESUMO Objetivo Descrever a implantação de um protocolo de atendimento nos moldes de times de resposta rápida, para manejo e resolução do sangramento. Métodos Foi idealizado e desenvolvido um protocolo institucional, chamado Código Hemorrágico, ou Código H, no qual, em um fluxo, um time multiprofissional e multidisciplinar foi constituído para atendimento integral, rápido e eficaz do paciente com doença hemorrágica grave. Em um outro fluxo, os profissionais, centralizados na farmácia do hospital, focavam na identificação do paciente com risco de hemorragia, no sentido de evitar o evento. Vários profissionais e setores do hospital foram treinados, e cada um, com funções específicas, deveria oferecer garantia total de apoio e suporte às equipes médica e de enfermagem. Resultados Após a implementação do protocolo, o número de eventos catastróficos relacionados à falha no manejo do sangramento reduziu significativamente. Conclusão O Código H é um exemplo de projeto de medicina baseada em valor e de medicina de precisão, por meio de atendimento integral e multidisciplinar, além de testes point of care introduzidos na prática clínica, com otimização da segurança do paciente e da prática assistencial na instituição. Ainda, por meio dele, deve ser possível minimizar o risco de ações judiciais para o hospital e os médicos, além de racionalizar recursos, com benefícios para administradores e fontes pagadoras.

Magnetic resonance cholangiopancreatography (mrcp) versus endosonography-guided fine needle aspiration (eus-fna) for diagnosis and follow-up of pancreatic intraductal papillary mucinous neoplasms / Análise comparativa entre colangiopancreatoressonância magnética (cprm) e punção ecoguiada com agulha fina (epaaf) para diagnóstico e seguimento das neoplasias intraductais mucinosas papilíferas pancreáticas

ABSTRACT Background: Intraductal papillary mucinous tumor (IPMN) are being diagnosed with increasing frequency. Computerized tomography scanning is commonly used as the primary imaging modality before surgery nonetheless magnetic resonance cholangiopancreatography (MRCP) provides better characterization. Endosonography-guided fine needle aspiration (EUS-FNA) has emerged as a way to reach pathological diagnose. Aim: To compare results of both methods with surgical pathology findings for classification of IPMN. Methods: Thirty-six patients submitted to surgical resection with preoperative suspect of IPMN were submitted preoperatively to MRCP and EUS-FNA. Images obtained were analyzed according to a classification determined for each method. ROC curve was used for statistical analysis, that compared the images tests with the purpose of finding the best method for diagnosis and classification of IPMN. Results: Sixteen patients underwent pancreatoduodenectomy, 16 to subtotal pancreatectomy and only four laparotomy. Pathological diagnosis was IPMN (n=33) and pancreatic intraepithelial neoplasia type 2 (n=3). Twenty-nine revealed non-invasive neoplasia and invasive form in four patients. MRCP and EUS-FNA have correctly diagnosed and classified (type of IPMN), in 62.5% and 83.3% (p=0.811), the affected segment location in 69% and 92% (p=0.638) and identification of nodules and/or vegetation presence in 45% and 90% (p=0.5). Regarding to histopathological diagnosis by EUS-FNA the sensitivity was 83.3%; specificity was 100%; positive predictive value was 100%; negative predictive value was 33.3% and accuracy was 91.7%. Conclusions: There was no significant difference in the diagnosis of IPMN. However, EUS-FNA showed better absolute results than MRCP to identify nodule and/or vegetation.

RESUMO Racional: A neoplasia intraductal mucinosa papilífera (NIMP) está sendo diagnosticada com maior frequência. O método mais utilizado para diagnóstico é a tomografia computadorizada. No entretanto, a colangiopancreatoressonância (CPRM) proporciona melhor caracterização tipo e extensão. A ecoendoscopia com punção por agulha fina (EPAAF), por sua vez, permite o diagnóstico histológico. Objetivo: Comparar resultados da CPRM e EPAAF com os achados cirúrgicos e patológicos para o diagnóstico e classificação da NIMP. Método: Foram estudados trinta e seis pacientes submetidos à ressecção cirúrgica por suspeita de NIMP que foram submetidos à CPRM e EPAAF pré-operatórias. Imagens obtidas por ambos os métodos foram analisadas utilizando-se padronização contendo o tipo e a classificação da lesão e os achados foram comparados, tendo como referência a análise patológica do espécime cirúrgico para definir-se qual o melhor método na caracterização do NIMP. Resultados: Vinte e nove revelaram neoplasia não-invasiva e quatro invasiva. A CPRM e a EPAAF fizeram o diagnóstico e classificaram corretamente (tipo de NIMP) em 62,5% e 83,3% (p=0,811), a localização do segmento pancreático acometido em 69% e 92% (p=0,638) e a identificação da presença de nódulos e/ou vegetações em 45% e 90 % (p=0,5). Quanto ao diagnóstico histológico pela EPAAF a sensibilidade foi 83,3%; especificidade 100%; VPP 100%; VPN 33,3%; e acurácia 91,7%. Conclusões: Os métodos diagnósticos não apresentaram diferença estatística. No entanto, a EPAAF mostrou resultados absolutos melhores do que a CPRM na identificação de nódulo e/ou vegetação intracístico.

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.

A new era of thromboelastometry / A nova era da tromboelastometria

ABSTRACT Severe hemorrhage with necessity of allogeneic blood transfusion is common complication in intensive care unit and is associated with increased morbidity and mortality. Prompt recognition and treatment of bleeding causes becomes essential for the effective control of hemorrhage, rationalizing the use of allogeneic blood components, and in this way, preventing an occurrence of their potential adverse effects. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time present limitations in predicting bleeding and guiding transfusion therapy in critically ill patients. Viscoelastic tests such as thromboelastography and rotational thromboelastometry allow rapid detection of coagulopathy and goal-directed therapy with specific hemostatic drugs. The new era of thromboelastometry relies on its efficacy, practicality, reproducibility and cost-effectiveness to establish itself as the main diagnostic tool and transfusion guide in patients with severe active bleeding.

RESUMO A hemorragia grave com necessidade de transfusão de sangue e componentes é uma complicação frequente na unidade de terapia intensiva e está associada ao aumento da morbidade e da mortalidade. A identificação adequada e o tratamento precoce da causa específica da coagulopatia tornam-se fundamentais para o controle efetivo da hemorragia, racionalizando a utilização de sangue e componentes, e desta forma, prevenindo a ocorrência de efeitos adversos. Testes convencionais da coagulação (tempo de ativação de protrombina e tempo de tromboplastina parcial ativada) apresentam limitações para prever sangramento e guiar a terapia transfusional em pacientes graves. Testes viscoelásticos como a tromboelastografia e tromboelastometria rotacional permitem a rápida detecção da coagulopatia e orientam a terapia de forma individualizada, alvo dirigida com drogas hemostáticas específicas. A nova era da tromboelastometria confia na sua eficácia, praticidade, reprodutibilidade e custo-eficácia para se firmar como a principal ferramenta diagnóstica e guia transfusional em pacientes com sangramento ativo grave.

Destaques do VII international symposium of thrombosis and anticoagulation (ISTA) / Highlights of VII international symposium of thrombosis and anticoagulation (ISTA)

O VII Simpósio Internacional de Trombose e Anticoagulação (ISTA) foi realizado em São Paulo, SP, Brasil, nos dias 24 e 25 de outubro de 2014, tendo como principais propósitos a discussão e o compartilhamento de conhecimentos sobre os avanços recentes na abordagem diagnóstica e terapêutica de pacientes com distúrbios trombóticos, nas suas diversas formas de apresentação clínica. O programa científico deste simpósio foi cuidadosamente desenvolvido por líderes de três importantes institutos de pesquisa clínica: o Instituto Brasileiro de Pesquisa Clínica(BCRI), o Duke Clinical Research Institute (DCRI), e Instituto de Pesquisa do Hospital do Coração. Composto por dois dias de apresentações acadêmicas e discussão aberta, o simpósio teve como principal objetivo educar, motivar e inspirar os clínicos, cardiologistas, hematologistas, e outros médicos através de apresentações e discussões de aspectos práticos de condutas que envolvem síndromes relacionadas à trombose e suas respectivas terapias antitrombóticas. Estas atividades possibilitaram uma interação direta entre a plateia e o corpo de palestrantes, composto por médicos de grande experiência clínica e pelos médicos pesquisadores que desenvolveram os principais estudos publicados que guiam nossas condutas em situações relacionadas ao tema "trombose e anticoagulação". Este artigo resume os anais deste simpósio.

The VII International Symposium on Thrombosis and Anticoagulation (ISTA) was held in São Paulo, Brazil, on 24 and 25 October 2014, with the main objectives to discuss and share knowledge on recent advances in the diagnosis and management of patients with thrombotic disorders. The scientific program of this symposium was carefully developed by leaders of three major clinical research institutes: the Brazilian Institute of Clinical Research (BCRI), the Duke Clinical Research Institute from Duke University, and the Research Institute from Hospital do Coração. Comprising two days of academic presentations and open discussion, the symposium aimed to educate, motivate and inspire clinicians, cardiologists, hematologists, and other doctors through presentations and discussions of practical aspects in themes related to thrombosis and anticoagulation. These activities were presented by physicians of great clinical experience and who participated in the main publications that guide our approach on situations related to the theme "thrombosis and anticoagulation". This article summarizes the proceedings of this symposium.

Vitamin D intoxication: case report / Intoxicação por vitamina D: relato de caso

Hypervitaminosis D is a rarely reported condition. In general it is only perceived when hypercalcemia is not resolved. The use of vitamin D has increased in recent years because of its benefits, but as a result, intoxication cases have occurred more frequently. This report describes a patient who presented worsening of renal function and hypercalcemia. After investigation, vitamin D intoxication was confirmed and it was due to an error in compounding.

A hipervitaminose D é pouco relatada. Geralmente, só é percebida quando o quadro de hipercalcemia não se resolve. Em razão de seus benefícios, o uso de vitamina D aumentou nos últimos anos; consequentemente, os casos de intoxicação também tiveram aumento. Este relato destacou um caso em que o paciente apresentava piora da função renal e hipercalcemia. Após investigação, ficou confirmada a intoxicação por vitamina D devido a um erro de manipulação da droga.

Implementation of vertical clinical pharmacist service on venous thromboembolism prophylaxis in hospitalized medical patients / Implantação do serviço do farmacêutico clínico vertical na profilaxia do tromboembolismo venoso em pacientes clínicos hospitalizados

Objective : To describe the vertical clinical pharmacist service’s interventions in prevention of venous thromboembolism. Methods : This prospective study was done at a private hospital. From January to May 2012, the clinical pharmacist evaluated medical patients without prophylaxis for thromboembolism. If the patient fulfilled criteria for thromboembolism and did not have contraindications, the clinical pharmacist suggested inclusion of pharmacologic agents and/or mechanical methods for venous thromboembolism prevention. In addition, the appropriate dose, route of administration, duplicity and replacement of the drug were suggested. Results : We evaluated 9,000 hospitalized medical patients and carried out 77 pharmaceutical interventions. A total of 71 cases (92.21%) adhered to treatment so that non-adherence occurred in 6 cases (7.79%). In 25 cases pharmacologic agents were included and in 20 cases mechanical prophylaxis. Dose adjustments, route, frequency, duplicity and replacement made up 32 cases. Conclusion : The vertical clinical pharmacist service included the prophylaxis for venous thromboembolism and promotion of appropriate use of medicines in the hospital. .

Objetivo : Descrever as intervenções do serviço do farmacêutico clínico vertical na prevenção do tromboembolismo venoso. Métodos : Estudo prospectivo, feito em hospital privado. Durante 5 meses, de janeiro a maio de 2012, o farmacêutico clínico avaliou os pacientes clínicos internados sem profilaxia para o tromboembolismo venoso. Se o paciente apresentasse critérios para desenvolver o tromboembolismo e não houvesse contraindicações para a profilaxia, o farmacêutico clínico sugeria a inclusão da profilaxia medicamentosa e/ou mecânica para equipe médica. Além disso, também foram feitas sugestões em relação à dose, via de administração, posologia, duplicidade terapêutica e substituição do medicamento profilático. Resultados : Foram avaliados 9.000 pacientes internados e feitas 77 intervenções farmacêuticas, houve adesão em 71 casos (92,21%); logo, a não adesão pelo médico ocorreu em 6 casos (7,79%). Em 25 casos houve a inclusão da profilaxia medicamentosa e, em 20 casos, a inclusão da profilaxia mecânica. Os ajustes de dose, via, frequência, duplicidade e substituição somaram 32 casos. Conclusão : A implantação do serviço do farmacêutico clínico vertical abrangeu a inclusão da profilaxia para tromboembolismo venoso e a promoção do uso correto de medicamentos no ambiente hospitalar. .

Fatores de risco hereditários e adquiridos na coagulação: impacto no desenvolvimento de eventos tromboembólicos em pacientes com lesão medular causada por trauma raquimedular / Hereditary and acquired clinical risk factors in the coagulation: impact in the development of thromboembolic events in patients with spinal injury caused by spinal cord injury

Objetivo: Avaliar o impacto de fatores de risco no desenvolvimento de eventos tromboembólicos em pacientes com lesão medular. Métodos: Estudo observacional, prospectivo e cruzado. Pacientes elegíveis (n=100) tinham lesão medular por trauma raquimedular e mais de 18 anos. O grau de lesão sensorial e motora foi avaliado com base na escala ASIA (ASIA Impairment Scale - AIS). Amostras de sangue foram coletadas para exames de coagulação, hemogramas, análises bioquímicas e laboratoriais. Exames de ultrassonografia foram realizados nos sistemas venosos superficial e profundo dos membros inferiores. Experimentos de PCR em tempo real foram realizados com o intuito de investigar mutações nos genes da protrombina (G20210A) e do fator V de Leiden (G1691A). Resultados: O principal achado deste estudo foi a maior ocorrência de Trombose Venosa Profunda (TVP) em pacientes com fator V de Leiden e hiperhomocisteinemia. Não houve associação entre Lesão Medular por TVP, Tromboembolismo Venoso (TEV) e trombofilia. Não houve também relação com lúpus anticoagulante e anti-cardiolipina. Conclusões: Houve importante diferença na incidência de TVP em pacientes com Lesão Medular, tanto aguda quanto crônica (após um ano da lesão). A investigação de trombofilia deve ter como base os fatores clínicos, fatores de risco para TVP e história familiar de trombose

Objective: Evaluate the impact of risk factors in the development of thromboembolic events in patients with spinal cord injury. Design: Observational, prospective and cross study. Eligible patients (n=100) had spinal injury (SI) by spinal cord injury (SCI), older than 18 years of age. The degree of motor and sensory lesion was evaluated based on ASIA Impairment Scale (AIS). Blood samples were collected for coagulation exams, hemogram, laboratory and biochemical analyses. Ultrasonography analyzes were performed from deep and superficial venous systems of lower limbs. Quantitative real-time PCR experiments were performed in order to investigate mutations in the prothrombin (G20210A) and Leiden factor V (G1691A) genes. Results: The main finding of this study was the higher occurrence of Deep Venous Thromboembolism (DVT) in patients with Leiden factor V and hyper homocysteinemia. There was no association between SI for DVT, venous thromboembolism (VT) and thrombophilia. Also, there was no relation between lupus anticoagulant and anti-cardiolipin. Conclusions: There is an important difference in the incidence of DVT in patients with SI by acute SCI and after 1 year. The conduct of the investigation for thrombophilia should be based on clinical factors, risk factors for DVT and family history of thrombosis

Transanal minimally invasive surgery with single-port (TAMIS) for the management of rectal neoplasms: a pilot study

Transanal endoscopic microsurgery (TEM) has been used since the 1980's for the treatment of selected rectal cancers, with clear benefits regarding morbidity and mortality, and good oncological outcomes when compared to radical surgery and conventional local resections. The high cost of equipment and the need for long learning curve did not allow the spread of the technique. The aim of this study was to describe the technical characteristics and outcomes of 4 patients operated by this technique, 3 with histologically confirmed adenomas and 1 carcinoid rectal tumor, with no recurrence after an average -follow-up of 12 months. The use of single port devices for transanal surgery is a safe method with good oncological results and allows a faster learning curve, by the similarity with conventional laparoscopic procedures and the availability of devices commonly used in laparoscopy. (AU)

A microcirurgia endoscópica transanal (TEM) é usada desde a década de 80 para o tratamento de neoplasias retais selecionadas, com claros benefícios relacionados à mortalidade e morbidade, e com bons resultados oncológicos, em comparação à cirurgia radical e a ressecções locais convencionais. O custo alto de equipamento de TEM e a necessidade de uma curva de aprendizagem longa ainda não permitiram a propagação da técnica. O objetivo deste estudo foi descrever a técnica cirúrgica e os desfechos oncológicos em 4 pacientes operados por esta técnica, 3 com diagnóstico final de adenomas e 1 de tumor carcinoide, sem recorrência após seguimento médio de 12 meses. A utilização de dispositivos de portal único para a cirurgia transanal é um método seguro e com bons resultados oncológicos, permitindo uma curva de aprendizado mais rápida pela semelhança com os procedimentos laparoscópicos convencionais e pela disponibilidade de dispositivos comumente utilizados em laparoscopia. (AU)

Plaquetopenias: diagnóstico usando citometria de fluxo e anticorpos antiplaquetas / Thrombocytopenia: diagnosis with flow cytometry and antiplatelet antibodies

Objective: To identify antiplatelet antibodies by flow cytometry (direct method) in patients with thrombocytopenia. Methods: Between January 1997 and March 2004 a total of 15100 patients were referred to the Centro de Hematologia de São Paulo for hematological investigation of several diagnoses (anemia, leukopenia, thrombocytopenia, coagulation abnormalities, adenomegaly, leukemia and others). Ofthose, 1057 were referred because of thrombocytopenia and were divided into two groups: Group Idiopathic thrombocytopenic purpura, with no identifiable cause; and Group Other thrombocytopenia, which included low normal platelet counts cause to be established, hepatitis C and HIV infection, hypersplenism, EDTA-induced artifacts, laboratory error, and other causes. Flow cytometry immunophenotyping was done in 115 cases to identify platelet autoantibodies (direct method). Results: Of the total number of patients, 1057 (7%) presented low platelet counts, 670 were females (63.4%) and age range of one to 75 years. Of the 115 cases (9.7%) submitted to immunophenotyping, the results were positive in 40% and the test was inconclusive in 5%. Idiopathic thrombocytopenic purpura was found in 52% of patients, more often in women. Hepatitis C virus infection was found in 7% and HIV infection in 1%. Low normal platelet counts were found in 17%, laboratory errors in 6%, and laboratory artifacts in 1% of cases. Platelet autoantibodies were found in 76.9% of all idiopathic thrombocytopenic purpura cases. It was negative in 83.3% of the low normal counts. Conclusion: antiplatelet autoantibodies when present help to diagnose idiopathic thrombocytopenic purpura. When absent, suggest other causes of thrombocytopenia.

Objetivo: Identificar anticorpos antiplaquetas por citometria de fluxo (método direto) em pacientes com plaquetopenia. Métodos: No período de Janeiro de 1997 a Março de 2004, foram encaminhados ao Centro de Hematologia de São Paulo 15.100 pacientes para investigação hematológica, com vários diagnósticos (anemia, leucopenia, plaquetopenia, alteração da coagulação, adenomegalias, leucemia e outros) dos quais 1.057 apresentavam plaquetopenia. Esses pacientes, conforme diagnóstico, foram separados em dois grupos: Grupo Púrpura Trombocitopênica Idiopática, quando não foi descoberta a etiologia da plaquetopenia; e Grupo Outra Trombocitopenia, que incluíafaixa de normalidade a esclarecer, infecção pelo vírus da hepatite C, HIV, hiperesplenismo, artefato EDTA, erro laboratorial e outras. Em 115 casos, foi realizada imunofenotipagem, para identificação de anticorpo antiplaquetas (método direto), por citometria de fluxo. Resultados: Dos 1.057 casos (7%) encaminhados por laquetopenia, 670 casos (63,4%) eram do sexo feminino. As idades variavam entre 1 e 75 anos. Dos 115 casos (9,7%) em que foi realizada imunofenotipagem, houve positividade em 40% e o exame foi duvidoso em 5%. A púrpura trombocitopênica idiopática foi encontrada em 52% dos casos, sendo mais frequente no sexo feminino, em crianças e adultos jovens. A prevalência do vírus da hepatite C foi encontrada em 7% dos casos e HIV em 1% dos casos. Faixa de normalidade foi encontrada em 17%; erro laboratorial em 6% e artefato laboratorial em 1% dos casos. Conclusão: O anticorpo antiplaquetas é um exame útil, quando positivo, para confirmar o diagnóstico de púrpura trombocitopênica idiopática e, quando negativo, sugere outras causas de trombocitopenia.