Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

Get With The Guidelines®-Stroke performance indicators in patients with transient ischemic attack / Indicadores de desempenho do programa "Get With The Guidelines®-Stroke" em pacientes com ataque isquêmico transitório

ABSTRACT Get With The Guidelines®-Stroke is an in-hospital program for improving stroke care by promoting adherence to scientific guidelines. Of the patients with transient ischemic attack (TIA), 10-15% have a stroke within three months, and many patients do not receive the recommended interventions to prevent this outcome. Objective: The goal of this study was to assess the adherence to stroke quality indicators in patients with TIA. Methods: This retrospective observational study evaluated consecutive patients admitted to a primary stroke center with TIA or acute ischemic stroke (AIS) from August 2008 to December 2013. Six quality indicators applicable to both TIA and AIS were analyzed and compared between groups. Results: A total of 357 patients with TIA and 787 patients with AIS were evaluated. Antithrombotic medication use within 48 hours of admission, discharge use of anticoagulation for atrial fibrillation and counseling for smoking cessation were similar between groups. In the TIA group, discharge use of antithrombotic medication (95% versus 98%; p = 0.01), lipid-lowering treatment (57.7% versus 64.1%; p < 0.01) and stroke education (56.5% versus 74.5%; p < 0.01) were all less frequently observed compared with patients with AIS. Conclusions: The adherence to some of the Get With The Guidelines®-Stroke quality indicators was lower in patients with TIA than in patients with AIS. Measures should be undertaken to reinforce the importance of such clinical interventions in patients with TIA.

RESUMO O "Get With The Guidelines®-Stroke (GWTG-S)" é um programa hospitalar criado para melhorar os cuidados em pacientes com AVC ao promover a adesão às diretrizes. Dez a quinze porcento dos pacientes com ataque isquêmico transitório terão um AVC em 3 meses, sendo que muitos não recebem intervenções de prevenção secundária recomendadas. Objetivo: Avaliar a adesão aos indicadores de qualidade do programa GWTG em pacientes com ataque isquêmico transitório. Métodos: Este estudo retrospectivo observacional avaliou pacientes consecutivos admitidos em um centro de AVC com suspeita de ataque isquêmico transitório ou AVC isquêmico agudo de agosto/2008 a dezembro/2013. Seis indicadores de qualidade aplicáveis tanto ao ataque isquêmico transitório quanto ao AVC isquêmico agudo foram analisados e comparados entre os grupos. Resultados: Um total de 357 pacientes com ataque isquêmico transitório e 787 pacientes com AVC isquêmico agudo foram avaliados. O uso de antiagregante dentro das primeiras 48 horas da admissão, liberação na alta com anticoagulante para fibrilação atrial e aconselhamento para cessação do tabagismo foram similares entre os grupos. No grupo com ataque isquêmico transitório, o uso de antiagregante na alta hospitalar, o tratamento com estatina e a educação sobre o AVC foram observados menos frequentemente quando comparados ao grupo de pacientes com AVC isquêmico agudo. Conclusões: A adesão a alguns dos indicadores de qualidade do programa GWTG-S foi mais baixa em pacientes com ataque isquêmico transitório quando compara a pacientes com AVC isquêmico agudo. Medidas devem ser tomadas para reforçar a importância dessas intervenções em pacientes admitidos com ataque isquêmico transitório.

Protective Effect of Ischemic Preconditioning on Myocardium Against Remote Tissue Injury Following Transient Focal Cerebral Ischemia in Diabetic Rats / Efeito Protetor do Pré-Condicionamento Isquêmico no Miocárdio Contra Lesão Remota de Tecidos após Isquemia Cerebral Focal Transitória em Ratos Diabéticos

Abstract Background: Remote ischemic preconditioning (IPreC) could provide tissue-protective effect at a remote site by anti-inflammatory, neuronal, and humoral signaling pathways. Objectives: The aim of the study was to investigate the possible protective effects of remote IPreC on myocardium after transient middle cerebral artery occlusion (MCAo) in streptozotocin- induced diabetic (STZ) and non-diabetic rats. Methods: 48 male Spraque Dawley rats were divided into eight groups: Sham, STZ, IPreC, MCAo, IPreC+MCAo, STZ+IPreC, STZ+MCAo and STZ+IPreC+MCAo groups. We induced transient MCAo seven days after STZ-induced diabetes, and performed IPreC 72 hours before transient MCAo. Remote myocardial injury was investigated histopathologically. Bax, Bcl2 and caspase-3 protein levels were measured by Western blot analysis. Total antioxidant status (TAS), total oxidant status (TOS) of myocardial tissue were measured by colorimetric assay. Oxidative stress index(OSI) was calculated as TOS-to-TAS ratio. For all statistical analysis, p values < 0.05 were considered significant. Results: We observed serious damage including necrosis, congestion and mononuclear cell infiltration in myocardial tissue of the diabetic and ischemic groups. In these groups TOS and OSI levels were significantly higher; TAS levels were lower than those of IPreC related groups (p < 0.05). IPreC had markedly improved histopathological alterations and increased TAS levels in IPreC+MCAo and STZ+IPreC+MCAo compared to MCAo and STZ+MCAo groups (p < 0.05). In non-diabetic rats, MCAo activated apoptotic cell death via increasing Bax/Bcl2 ratio and caspase-3 levels. IPreC reduced apoptotic cell death by suppressing pro-apoptotic proteins. Diabetes markedly increased apoptotic protein levels and the effect did not reversed by IPreC. Conclusions: We could suggest that IPreC attenuates myocardial injury via ameliorating histological findings, activating antioxidant mechanisms, and inducing antiapoptotic activity in diabetic rats.

Resumo Fundamentos: O pré-condicionamento isquêmico remoto (IPreC) poderia fornecer efeito protetor de tecido em um local remoto por vias de sinalização anti-inflamatórias, neuronais e humorais. Objetivos: O objetivo do estudo foi investigar os possíveis efeitos protetores do IPreC remoto no miocárdio após a oclusão transitória da artéria cerebral média (MCAo) em ratos com diabetes induzida por estreptozotocina (STZ) e ratos não diabéticos. Métodos: 48 ratos Spraque Dawley machos foram divididos em oito grupos: grupos Sham, STZ, IPreC, MCAo, IPreC + MCAo, STZ + IPreC, STZ + MCAo e STZ + IPreC + MCAo. Induzimos MCAo sete dias após a diabetes induzida por STZ e realizamos IPreC 72 horas antes do MCAo. A lesão miocárdica remota foi investigada histopatologicamente. Os níveis de proteína Bax, Bcl2 e caspase-3 foram medidos pela análise Western Blot. O estado de antioxidante total (TAS), e o estado de oxidação total (TOS) do tecido miocárdico foram medidos por meio de um estudo colorimétrico. O índice de estresse oxidativo (OSI) foi calculado como a relação TOS-TAS. Para todas as análises estatísticas, os valores de p < 0,05 foram considerados significativos. Resultados: Observamos danos graves, incluindo necrose, congestão e infiltração de células mononucleares no tecido miocárdico dos grupos diabético e isquêmico. Nesses grupos os níveis de TOS e OSI foram significativamente maiores; os níveis de TAS foram inferiores aos dos grupos relacionados com IPreC (p < 0,05). O IPreC melhorou marcadamente as alterações histopatológicas e aumentou os níveis de TAS em IPreC + MCAo e STZ + IPreC + MCAo em comparação com os grupos MCAo e STZ + MCAo (p < 0,05). Em ratos não diabéticos, MCAo activou a morte celular apoptótica através do aumento da relação Bax / Bcl2 e dos níveis de caspase-3. IPreC reduziu a morte celular apoptótica pela supressão de proteínas pró-apoptóticas. O diabetes aumentou acentuadamente os níveis de proteína apoptótica e o efeito não foi revertido pelo IPreC. Conclusões: Podemos sugerir que o IPreC atenua a lesão miocárdica através da melhora dos achados histológicos, ativando mecanismos antioxidantes e induzindo atividade antiapoptótica em ratos diabéticos.

The Role of Histone Deacetylase Inhibitors in Regulation of Akt/GSK-3ß Signaling Pathway in Mice Following Transient Focal Cerebral Ischemia

Abstract Purpose: To investigate whether the neuroprotective effect of TSA on cerebral ischemia reperfusion injury is mediated by the activation of Akt/GSK-3β signaling pathway. Methods: Mice were randomly divided into four groups (n=15): sham group (S); ischemia reperfusion group (IR); ischemia reperfusion and pretreated with TSA group (IR+T); ischemia reperfusion and pretreated with TSA and LY294002 group (IR+T+L). The model of cerebral ischemia reperfusion was established by 1h of MCAO following 24h of reperfusion. TSA (5mg/kg) was intraperitoneally given for 3 days before MCAO, Akt inhibitor, LY294002 (15 nmol/kg) was injected by tail vein 30 min before the MCAO. Results: TSA significantly increased the expression of p-Akt, p-GSK-3β proteins and the levels of SOD, Bcl-2, reduced the infarct volume and the levels of MDA, ROS, TNF-α, IL-1β, Bax, Caspase-3, TUNEL and attenuated neurological deficit in mice with transient MCAO, LY294002 weakened such effect of TSA dramatically. Conclusions: TSA could significantly decrease the neurological deficit and reduce the cerebral infarct volume, oxidative stress, inflammation, as well as apoptosis during cerebral ischemia reperfusion injury, which was achieved by activation of the Akt/GSK-3β signaling pathway.

Accidente isquémico transitorio de causa hemodinámica / Transient ischemic attack of hemodynamic cause

El síncope es una perdida súbita y transitoria del estado de conciencia y el tono postural con restitución completa. Según su etiología se clasifica como reflejo (neuromediado), cardíaco, neurológico (isquemia vertebrobasilar) o indeterminado. Los síncopes neurológicos se observan en contexto de accidente cerebrovascular isquémico o accidente isquémico transitorio; frecuentemente se asocian a signos deficitarios focales. Presentamos el caso de un síncope no neurológico con signos deficitarios focales en una paciente con marcada enfermedad ateromatosa. (AU)

Syncope is the abrupt and transient loss of consciousness associated with absence of postural tone, followed by complete and usually rapid spontaneous recovery. In terms of etiology, syncope is classified as reflex (neurally mediated), cardiac, neurologic (vertebrobasilar ischemia) or indeterminate. The neurologic syncope occurs in the setting of stroke or transient ischemic attack, being most frequently associated with focal neurologic symptoms. We report a case of non-neurologic syncope followed with focal neurologic symptoms in a patient with atherosclerosis disease. (AU)

Score for atrial fibrillation detection in acute stroke and transient ischemic attack patients in a Brazilian population: The acute stroke atrial fibrillation scoring system

OBJECTIVE: Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings. METHODS: We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS). RESULTS: A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76). CONCLUSIONS: Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement. .

Avoiding pitfalls in diagnosing basilar artery occlusive disease: clinical and imaging clues - case report / Evitando erros no diagnóstico de doença oclusiva da artéria basilar: pistas clínicas e radiológicas - relato de caso

CONTEXT: The aim of this paper was to report on the characteristics that aid in establishing the diagnosis of basilar artery occlusive disease (BAOD) among patients with hemiparesis and few or minor symptoms of vertebrobasilar disease. CASE REPORT: This report describes two cases in a public university hospital in São Paulo, Brazil. We present clinical and imaging findings from two patients with hemiparesis and severe BAOD, but without clinically relevant carotid artery disease (CAD). One patient presented transient ischemic attacks consisting of spells of right hemiparesis that became progressively more frequent, up to twice a week. The neurological examination revealed slight right hemiparesis and right homonymous hemianopsia. Magnetic resonance imaging (MRI) revealed pontine and occipital infarcts. Magnetic resonance angiography and digital subtraction angiography revealed severe basilar artery stenosis. The other patient presented sudden left-side hemiparesis and hypoesthesia. One year earlier, she had reported sudden onset of vertigo that, at that time, was attributed to peripheral vestibulopathy and was not further investigated. MRI showed a right-side pontine infarct and an old infarct in the right cerebellar hemisphere. Basilar artery occlusion was diagnosed. Both patients presented their symptoms while receiving aspirin, and became asymptomatic after treatment with warfarin. CONCLUSIONS: Misdiagnosing asymptomatic CAD as the cause of symptoms in BAOD can have disastrous consequences, such as unnecessary carotid endarterectomy and exposure to this surgical risk while failing to offer the best available treatment for BAOD. Clinical and imaging features provided important clues for diagnosis in the cases presented.

CONTEXTO: O objetivo deste artigo foi de relatar as características que auxiliam no estabelecimento do diagnóstico da doença oclusiva da artéria basilar (DOAB) em pacientes com hemiparesia e poucos sintomas, ou sintomas leves de doença vertebrobasilar. RELATO DE CASO: Descrição de dois casos em um hospital público universitário em São Paulo, Brasil. Apresentamos características clínicas e radiológicas de dois pacientes com hemiparesia e DOAB grave, na ausência de doença carotídea (DCA) relevante. Um paciente apresentou ataques isquêmicos transitórios consistindo de hemiparesia direita transitória, que se tornaram progressivamente mais frequentes, até duas vezes por semana. O exame neurológico revelou hemiparesia direita e hemianopsia homônima direita. A ressonância magnética (RM) revelou infartos pontinos e occipitais. As angiografias por ressonância magnética e por subtração digital revelaram estenose grave da artéria basilar. Outra paciente apresentou hemiparesia e hipoestesia de instalação súbita, à esquerda. Um ano antes, ela havia apresentado vertigem súbita, na ocasião atribuída a vestibulopatia periférica, não investigada em maior profundidade. A RM mostrou infarto pontino à direita e infarto antigo no hemisfério cerebelar direito. Foi diagnosticada oclusão da artéria basilar. Ambos os pacientes apresentaram os sintomas enquanto faziam tratamento com aspirina, e se tornaram assintomáticos após tratamento com warfarina. CONCLUSÕES: O diagnóstico errôneo de DCA como causa de sintomas na DOAB pode ter conseqüências desastrosas, como a endarterectomia carotídea desnecessária e a exposição a tal risco cirúrgico, ao invés de oferecimento do melhor tratamento disponível para a DOAB. Características clínicas e radiológicas forneceram pistas importantes para o diagnóstico nos casos apresentados.

Isquemia cerebral transitoria y riesgo de infarto cerebral isquémico / Transitory cerebral isquemia and risk of cerebral ischemic stroke

La enfermedad vascular cerebral es la principal causa de hospitalización neurológica en el mundo. Costa Rica no es la excepción; en nuestros hospitales cada día es más frecuente el número de pacientes que ingresan con infartos cerebrales isquémicos. Esta común enfermedad obedece a la prevalencia de enfermedades crónicas con la hipertensión arterial, diabetes mellitus, dislipidemias, tabaquismo y la alta expectativa de vida de los costarricenses, todos considera dos factores de riesgo. Aproximadamente un 80 por ciento de los infartos cerebrales son isquémicos secundarios a la oclusión arterial aguda de un territorio vascular específico, el restante 20 por ciento corresponde a la variante hemorrágica. Las secuelas neurológicas secudarias a esta entidad son la principal causa de discapacidad crónica en los pacientes y conlleva una alta morbilidad y mortalidad. Aunque muchos sufren el infarto cerebral isquémico en forma aguda, otro grupo de pacientes experimenta uno o varios episodios previos de isquemia cerebral transitoria, lo cual los pone en riesgo de sufrir un infarto cerebral isquémico durante un periodo corto, es decir son pacientes vulnerables. Esta revisión pretende actualizar los conocimientos médicos, especialmente para aquellos que trabajan en la atención primaria y en los servicios de urgencias hospitalarias, que reconozcan a este grupo de pacientes y les brinden la atención médica necesaria para de prevenir un infarto cerebral isquémico. La isquemia cerebral transitoria debe ser considerada como una emergencia neurológica. Descriptores: Isquemia cerebral transitoria, emergencia neurológica, infarto cerebral isquémico.

Valoración y tratamiento de la isquemia cerebral transitoria y del déficit neurológico isquémico menor

La elucidación del mecanismo patogénico específico responsable de un cuadro de isquemia cerebral transitoria o de déficit neurológico isquémico menor permite por lo general predecir el riesgo subsiguiente de accidente cerebrovascular con mayor certidumbre que la pura y simple descripción de inumerables detalles sobre la presentación clínica del evento.

Hemorragia subaracnoidea - parte II: o papel do tratamento clinico / subarchnoid hemorrhage - part II: the role of clinical treatment

A hemorragia subaracnoidea (HSA) representa um grande desafio terapeutico para neurocirurgioes, neurologistas e intensivistas. Estes profissionais estao decepcionados com ressangramentos fatais no pre-operatorio e operatoria imediata, seguem um curso intratavel fatal em decorrencia do vasoespasmo. O assunto e extenso e muitas vezes controverso. Com objetivo de tentar sistematizar o tratamento e talvez servir de base para o estabelecimento de um protocolo funcional,, os autores fazem uma revisao dos artigos mais recentes sobre o tema mas baseiam-se principalmente na conduta adotada por F. Espinosa, B. Weir e T. Noseworth no Hospital Royal Alexandra de Alberta, Canada.

Neuropéptidos Vasculares y Vasoespasmo Cerebral

A nivel de Sistema Nervioso Central coexisten múltiples neurotransmisores y neuromoduladores que a través de complejas interrelaciones participan en la regulación del flujo y perfusión cerebral tanto en condiciones normales como patológicas. A continuación se revisarán los principales neuropéptidos vasculares reconocidos hasta el momento, que participan en esta regulación

Aspectos fisiopatológicos do vasoespasmo cerebral por aneurisma intracraniano roto / Physiopathological aspects of cerebral vasospasm by ruptured intracranial aneurysm

Os autores näo pretendem esgotar nem a literatura pertinente ao tema nem o próprio assunto, mas a revisäo do täo controverso tema foi realizada, no sentido de compreender os mecanismos pelos quais a hemorragia subaracnóidea proporciona a täo temida angiopatia decorrentes do sangramento de aneurisma sacular intracraniano, responsável pelo óbito de 30% dos pacientes, mesmo submetidos a tratamento clínico e cirúrgico

Correlation of postural and pathological findings in a modified four-vessel occlusion model of rat forebrain ischemia

The Pulsinelli preparation has largely simplified and avoided the complications of other models of brain ischemia in the rat. We present here modifications which improve the Pulsinelli preparation, based on a new and atraumatic technique for arterial clamping. Effective cauterization of vertebral arteries was obtained using a modified pyrographic device. Histopathological results demonstrate that the modified method was capable of reproducing the features of transient forebrain ischemia reported in the literature. Consistent postural changes were induced by the ischemic insult. The intensity and interhemispheric symmetry of brain damage correlated well with the occurrence and maintenance of postural alterations throughout the ischemic period as well as with the duration of the latter

Vasoespasmo cerebral: fisiopatología y tratamiento / Cerebral vasoespasm: physiopathology and treatment

El vasoespasmo cerebral es un fenómeno que complica frecuentemente la hemorragia subaracnoídea secubdaria a un aneurisma cerebral roto, presentándose en el 40-50% durante su curso clínico. Existen algunos hechos comunes a los casos que se complican con un vasoespasmo: a) Hay un "intervalo libre" de 2 a 3 días entre la ruptura del aneurisma y la aparición del déficit isquémico neurológico retardado. b) Este déficit isquémico retardado siempre se correlaciona con la presencia de coágulos sanguíneos en el espacio subaracnoídeo, alrededor de las arterias de la base del cerebro. c) Mientras mayor sea la cuantía del sangramiento y por ende, de los coágulos en el espacio subaracnoídeo, mayor es la posibilidad de desarrollo de un vasoespasmo. En esta revisión se detallan las posibilidades etiopatogénicas y fisiopatológicas más aceprtadas, como explicación a este debatido e importante fenómeno y se reseñan las tentativas terapéuticas más en boga

Vasoespasmo cerebral en hemorragia subaracnoidea debida a ruptura de aneurisma / Cerebral vasospasm in subarachnoid hemorrhage due to a ruptured aneurysm

El pronóstico de la hemorragia subaracnoidea depende de una serie de factores, pero principalmente de la cantidad de sangre derramada y el eventual resangrado, que determinan el estado general del paciente y conducen al espasmo arterial. El lugar de la ruptura, la presión intracreneana, eventualmente un hematoma intracerebral, también participan en la determinación de ese pronóstico, así como la edad del paciente y otras enfermedades que coincidentemente éste pueda padecer. La cirugía precoz, clipando el aneurisma y evacuando coágulos, puede evitar en buena medida al resangrado y al espasmo. El LCR escaso o carente de una cantidad de dispositivos metabólicos que en el resto del organismo impiden la producción de radicales libres, los que a su vez producen la preoxidación de lípidos, causa muy probable del espasmo arterial. A la cirugía precoz pueden agregarse medicamentos que protejan al cerebro de la isquemia, drogas recolectoras de radicales libres y otras que disminuyan su producción, antagonistas del calcio, etc