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1.
Rev. neurol. (Ed. impr.) ; 57(9): 411-421, 1 nov., 2013.
Artigo em Espanhol | IBECS | ID: ibc-117508

RESUMO

El rivaroxaban es un inhibidor oral altamente selectivo del factor Xa. Actualmente, el uso de rivaroxaban está aprobado para la prevención del tromboembolismo venoso en adultos a los que se va a realizar un reemplazo electivo tanto de rodilla como de cadera, para el tratamiento de la trombosis venosa profunda y embolia de pulmón y la prevención secundaria a largo plazo del tromboembolismo venoso, y para la prevención del ictus y del embolismo sistémico en pacientes con fibrilación auricular no valvular. El rivaroxaban posee múltiples ventajas sobre los antagonistas de la vitamina K, y esto puede facilitar su uso en la práctica clínica. En consecuencia, es probable que los nuevos anticoagulantes cambien las estrategias de manejo de los pacientes que requieran anticoagulación. Por otra parte, el rivaroxaban tiene algunas particularidades que es necesario conocer. El objetivo de este articulo ha sido revisar el uso del rivaroxaban no solo en la población general, sino también en diferentes subgrupos de pacientes y situaciones clínicas, para así lograr un manejo óptimo de este fármaco en la práctica clínica diaria (AU)


Rivaroxaban is an oral highly selective direct factor Xa inhibitor. Rivaroxaban is currently approved for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery, for the treatment of deep vein thrombosis and pulmonary embolism and long-term secondary prevention of venous thromboembolism, and for stroke and systemic embolism prevention in patients with nonvalvular atrial fibrillation. Rivaroxaban has many advantages over vitamin K antagonists and this may facilitate its use in clinical practice. As a result, it is expected that new oral anticoagulants may change patient management strategies. On the other hand, rivaroxaban has some particularities that are necessary to know. The aim of this manuscript was to review the use of rivaroxaban not only in general population, but also in specific patients groups and clinical situations to achieve an optimal management with this drug in daily clinical practice (AU)


Assuntos
Humanos , Fator Xa/antagonistas & inibidores , Tromboembolia Venosa/prevenção & controle , Osteoartrite/cirurgia , Cuidados Pré-Operatórios/métodos , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico
2.
Mem. Inst. Oswaldo Cruz ; 108(6): 679-685, set. 2013. graf
Artigo em Inglês | LILACS | ID: lil-685490

RESUMO

Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.


Assuntos
Animais , Humanos , Coagulação Sanguínea/fisiologia , Leishmania/metabolismo , Fosfatidilserinas/metabolismo , Psychodidae/parasitologia , Saliva/metabolismo , Anticoagulantes/metabolismo , Cisteína Endopeptidases , Fator V/antagonistas & inibidores , Fator X/antagonistas & inibidores , Fator Xa/antagonistas & inibidores , Insetos Vetores/parasitologia , Proteínas de Neoplasias/antagonistas & inibidores , Tempo de Tromboplastina Parcial , Fosfatidilcolinas/metabolismo , Psychodidae/metabolismo , Trombina/antagonistas & inibidores , Extratos de Tecidos/metabolismo
4.
Nefrología (Madr.) ; 32(5): 605-612, sept.-oct. 2012. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-106150

RESUMO

Introducción: Los sistemas de hemodiálisis tienen capacidad trombogénica, por lo que se utiliza de forma rutinaria la anticoagulación. Su prescripción no se encuentra exenta de riesgos, a pesar de lo cual las recomendaciones respecto a la dosis pautada siguen basándose en criterios muy diversos. Métodos: Se realizó un estudio experimental aleatorizado y cruzado. Seis pacientes realizaron seis sesiones de hemodiafiltración posdilución con el dializador de polisulfona HF80® y anticoagulación habitual con nadroparina, y seis sesiones con el dializador AN69ST® de poliacrilonitrilo con una cubierta de heparina sin el uso de anticoagulación sistémica. Evaluamos cada hora el grado de coagulación del dializador y del circuito extracorpóreo mediante una escala visual y las variaciones en los parámetros de coagulación, entre los que se incluyó el factor anti-Xa. Nuestro objetivo primario fue valorar las variaciones en la actividad del factor anti-Xa en ausencia de diferencias en la tasa de coagulación masiva entre los dos grupos. Resultados: No se coaguló el dializador de forma completa o grado 4 en ninguna de las 36 sesiones realizadas con cada dializador. Se produjo una coagulación parcial del dializador inferior del 25% (grado 1-2) en 32 (88,9%) sesiones con AN69ST® y 35 (97,2%) con el dializador habitual, y superior del 25% (grado 3-4) en 4 (11,1%) sesiones con AN69ST® y en 1 (2,8%) sesión con el dializador con heparina. La coagulación del atrapaburbujas arterial no fue superior al 25% (grados 3 y 4) en ninguna de las sesiones estudiadas, y la cámara venosa en sólo 1 (2,8%) sesión con el dializador habitual y 3 (8,4%) con AN69ST® sin diferencias entre los dos dializadores. El (..) (AU)


Background: Haemodialysis systems are potentially thrombogenic, so anticoagulation is routinely used. Its prescription involves certain risks, despite which the recommendations regarding dosage are still based on very disparate criteria. Methods: We performed a randomised, crossed pilot study. Six patients underwent six sessions of post-dilution haemodiafiltration with a polysulfone HF80® dialyser and standard anticoagulation with nadroparin, and six sessions with heparincoated poliacrylonitrile AN69ST® membrane without the administration of systemic anticoagulation therapy. The coagulation level of the dialyser and extracorporeal circuit was evaluated every hour using a visual scale along with variation in clotting parameters such as anti-Xa factor. Our primary objective was to assess anti-Xa activity in the absence of differences in the rate of massive coagulation between the two groups. Results: No complete or grade 4 dialyser clotting occurred in any of the 36 sessions with either dialyser. Partial clotting of the dialyser occurred below 25% (grade 1-2) in 32 (88.9%) AN69ST® sessions and 35 (97.2%) sessions using the standard dialyser, and partial clotting surpassed 25% (grade 3-4) in 4 (11.1%) AN69ST® sessions and 1 (2.8%) dialysis session with heparin. Arterial chamber blood clotting did not surpass 25% (grade 3 and 4) in any of the studied sessions, and venous chamber coagulation occurred in only 1 (2.8%) session with the usual dialyser and in 3 (8.4%) sessions with the AN69ST®, with no significant differences between the two (..) (AU)


Assuntos
Humanos , Insuficiência Renal Crônica/terapia , Diálise Renal/instrumentação , Soluções para Diálise/farmacologia , Hemodiafiltração/métodos , Fator Xa/antagonistas & inibidores , Heparina/uso terapêutico , Anticoagulantes/uso terapêutico , Hemorragia/prevenção & controle
5.
Rev. neurol. (Ed. impr.) ; 55(1): 11-19, 1 jul., 2012. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-101762

RESUMO

Introducción. Un 40% de los pacientes con anticoagulación oral no iniciaría el tratamiento con antagonistas de la vitamina K por la necesidad de controles periódicos y sus interferencias con la dieta y medicación concomitante. Objetivo. Analizar las preferencias de los pacientes con fibrilación auricular no valvular por anticoagulantes orales (AO) para la prevención del ictus. Pacientes y métodos. Estudio observacional, transversal, multicéntrico, de preferencias y disponibilidad a pagar: se definieron los atributos de los AO mediante revisión de la bibliografía, grupos focales y entrevistas semiestructuradas con médicos y pacientes. Posteriormente, se definieron escenarios que los pacientes ordenaron según sus preferencias. Se analizaron los datos de la muestra total y por conglomerados agrupados por sus preferencias. Resultados. Se definieron ocho escenarios basados en cinco atributos: eficacia, seguridad, dosis fija, necesidad de controles de la coagulación, e interacciones con la dieta y medicación. Se entrevistó a 295 pacientes ambulatorios (edad media: 71,76 ± 9,81 años) que recibían AO. El atributo preferido fue el ‘menor número de embolias/año’ (importancia: 30,15%), seguido de ‘dosis fija del AO’ (25,45%) y ‘menor número de hemorragias intracraneales anuales’ (21,57%). En la muestra se identificaron tres segmentos de población con preferencias diferentes. La máxima disponibilidad a pagar (media) por un AO fue 66,76 ± 54,64 euros mensuales. Conclusiones. Eficacia, dosis fija y seguridad son los atributos de los AO más valorados por los pacientes con fibrilación auricular no valvular. Estas preferencias deberían considerarse al instaurar o cambiar el tratamiento con AO para mejorar el cumplimiento y prevención en pacientes (AU)


Introduction. About 40% of patients who receive oral anticoagulation would not start treatment with vitamin K antagonists due to the regular control they require and their interference with the diet and other concomitant medications. Aim. To analyze the preferences of patients with non valvular atrial fibrillation for oral anticoagulants (OAs) for the stroke prevention. Patients and methods. Observational, multicentric study on preferences and maximum willingness to pay based on conjoint analysis: literature review, focus groups and semi-structured interviews with physicians and patients (n = 295) to define the attributes of OAs and their levels. Definition of scenarios that patients ordered according to their preferences. Clusters analysis to identify population groups by their preferences. Results. Eight scenarios were defined based on five attributes: efficacy, security, a fixed dose, need for coagulation controls and interactions with diet and medication. The most preferred attribute was the smaller number of embolisms in a year (importance: 30.15%) followed by the fixed dose of the OA (25.45%) and the smaller number of intracranial hemorrhage in a year (21.57%). Three clusters population were identified. The maximum amount patients’ were willingness to pay for the OA was 66.76 ± 54.64 euros (mean) per month. Conclusions. Efficacy and a fixed dose are the attributes of OA most valued by non valvular atrial fibrillation patients. There are groups of patients who differ in their preferences. This differences should be taken into account when deciding instauration or change on the OA treatment to ameliorate the accomplishment and prevention in this patients (AU)


Assuntos
Humanos , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Fibrilação Atrial/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Fator Xa/antagonistas & inibidores , Trombina/antagonistas & inibidores
6.
Rev. méd. Chile ; 139(10): 1347-1355, oct. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-612205

RESUMO

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.


Assuntos
Humanos , Anticoagulantes/classificação , Fator Xa/antagonistas & inibidores , Trombina/antagonistas & inibidores , Vitamina K/antagonistas & inibidores , Administração Oral
7.
Angiología ; 62(1): 26-32, ene.-feb. 2010. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-85803

RESUMO

Después de realizar una perspectiva histórica de los anticoagulantes, se relatan los problemas ylas limitaciones de los actuales, para posteriormente hacer una clasifi cación de los nuevos.El presente artículo de revisión focaliza su atención en los nuevos anticoagulantes orales. Setrata de una apuesta importante de la industria farmacéutica por unos anticoagulantes de administraciónoral, inicio de actividad precoz y una diana específi ca y directa anti-Xa o anti-IIa.Los productos que poseen el desarrollo clínico más avanzado son dabigatran etexilato y rivaroxaban.Se concluye que aunque los nuevos anticoagulantes orales son muy atractivos por diversas razones,todavía no sabemos cuándo reemplazarán a los anticoagulantes convencionales. Cada potencialindicación específica requerirá de nuevas y numerosas investigaciones(AU)


After carrying out a historical review of anticoagulants, the problems and limitations of currentanticoagulants are discussed, and the new anticoagulants are subsequently classify.This review article focuses on new oral anticoagulants. This represents a major commitment bythe pharmaceutical industry with some oral, fast-acting, specifi c target and direct anti-Xa oranti-IIa anticoagulants. Products such as dabigatran etexilate and rivaroxaban are in moreclinically advanced stages of development.It concludes that, although the new oral anticoagulants are more attractive for various reasons,we still do not know when they will replace conventional anticoagulants. Each specifi c potentialindication will need to be defi ned along with many studies(AU)


Assuntos
Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/história , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapêutico , Medicamentos de Referência , Administração Oral , Fator Xa/antagonistas & inibidores , Inibidores dos Fatores de Coagulação Sanguínea/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Vitamina K/antagonistas & inibidores
9.
Farm. hosp ; 33(3): 125-133, mayo-jun. 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-105292

RESUMO

Dabigatran es el primer anticoagulante inhibidor directo de la trombina disponible por vía oral. La absorción del profármaco dabigatran etexilato y su conversión a dabigatran es rápida (concentraciones máximas de 4-6 h tras cirugía y 2 h posteriormente) y, pese a la baja biodisponibilidad oral, presenta escasa variabilidad entre individuos. Inhibe específica y reversiblemente la trombina, la enzima llave de la cascada de la coagulación. Los estudios tanto en voluntarios sanos como en pacientes sometidos a cirugía ortopédica mayor muestran un perfil pk/pd predecible, lo que permite regímenes fijos de dosificación. El efecto anticoagulante se correlaciona bien con las concentraciones plasmáticas del fármaco, lo que aúna una efectiva anticoagulación con un bajo riesgo de hemorragia. La excreción es mayoritariamente renal (lo que condiciona su dosificación en pacientes ancianos y con insuficiencia renal), y no sufre metabolismo hepático por el sistema del citocromo P450, por lo que presenta un perfil de fármaco sin grandes problemas de interacción con otros medicamentos. Rivaroxaban será probablemente el primer fármaco anticoagulante oral inhibidor directo del factor Xa (FXa) disponible. Produce una inhibición reversible y predecible de la actividad del FXa con capacidad de inhibir el FXa ligado al coágulo. Sus características farmacocinéticas incluyen rápida absorción, con elevadas biodisponibilidad y unión a proteínas plasmáticas y semivida de eliminación de, aproximadamente, 8 h. La eliminación es de tipo dual, renal (mayoritaria) y biliar. Aunque ha demostrado tener un potencial moderado de interacción con inhibidores fuertes del citocromo P450-A4, no parece inhibir ni inducir ninguna enzima P450 (AU)


Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme (AU)


Assuntos
Humanos , Anticoagulantes/farmacocinética , Trombina/antagonistas & inibidores , Fator Xa/antagonistas & inibidores , Interações Medicamentosas , Fibrinolíticos/farmacocinética , Disponibilidade Biológica
10.
Braz. j. med. biol. res ; 39(11): 1409-1415, Nov. 2006. graf, tab
Artigo em Inglês | LILACS | ID: lil-437832

RESUMO

In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10 percent of mammalian heparin and about 5 percent as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porcine heparin in rat models of venous thrombosis and blood loss. Intravenous administration of the oocyte test cell heparin to Wistar rats (both sexes, weighing ~300 g, N = 4 in each group) at a dose of 5.0 mg/kg body weight, which produced a 1.8-fold increase in plasma activated partial thromboplastin time, inhibited thrombosis by 45 ± 13.5 percent (mean ± SD) without any bleeding effect. The same dose of porcine heparin inhibited thrombosis by 100 ± 1.4 percent, but produced a blood loss three times greater than that of the saline-treated control. However, 10-fold reduction of the dose of porcine heparin to 0.5 mg/kg body weight, which produced a 5-fold increase in plasma-activated partial thromboplastin time, inhibited thrombosis by 70 ± 13 percent without any bleeding effect. The antithrombotic properties of a new heparin isolated from test cells of the sea squirt S. plicata, reported here for the first time, indicate that, although sea squirt oocyte test cell heparin was a poor anticoagulant compared to porcine heparin, it had a significant antithrombotic effect without causing bleeding.


Assuntos
Animais , Masculino , Feminino , Ratos , Anticoagulantes/isolamento & purificação , Antitrombinas/isolamento & purificação , Heparina/isolamento & purificação , Oócitos/química , Urocordados/química , Trombose Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Modelos Animais de Doenças , Fator Xa/antagonistas & inibidores , Hemorragia/tratamento farmacológico , Heparina/uso terapêutico , Tempo de Tromboplastina Parcial , Ratos Wistar , Suínos , Urocordados/citologia
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