Acute myocardial infarction after switching from warfarin to dabigatran

Dabigatran etexilate is a recently approved direct thrombin inhibitor [DTI], which is superior to warfarin in the prevention of stroke and systemic embolism in patients with atrial fibrillation [AF]. However, dabigatran use is associated with an increased risk of myocardial infarction [MI] compared to warfarin. The mechanisms for this association effect remain speculative. We present a case of an acute MI and cardiac arrest in a patient with chronic AF who had been recently switched from warfarin to dabigatran. Urgent coronary angiography, at St. Michael's hospital [Toronto, Canada], revealed evidence of thromboembolism to the distal posterior descending artery. The patient was treated medically and switched back from dabigatran to warfarin. He did well and was discharged after an uneventful stay in the coronary care unit

Comportamentos e práticas sexuais de homens que fazem sexo com homens / Sexual behaviors and practices of men who have sex with men / Conductas y prácticas sexuales de los hombres que tienen sexo con hombres

Objetivou-se identificar comportamentos e práticas sexuais de homens que fazem sexo com homens no contexto da vulnerabilidade ao HIV/AIDS. Estudo transversal, exploratório descritivo. Foi realizado em um local de sociabilidade gay de Fortaleza, no Estado do Ceará, entre novembro de 2010 e março de 2011, por meio de entrevista com 189 homens que fazem sexo com homens. Encontrou-se uma amostra composta, majoritariamente, por jovens, solteiros e com alto nível educacional. A história sexual demonstrou o início precoce da vida sexual, com prevalência elevada de relação sexual com parceira do sexo oposto. Houve alta frequência de testagem para o HIV. As práticas sexuais revelaram prevalência superior da realização de sexo oral e anal, bem como altos níveis de proteção no sexo anal, apesar de baixa no sexo oral. Constatou-se uma maior incorporação das práticas de prevenção em relação ao panorama nacional do início da epidemia.

The objective was to identify behaviors and sexual practices of men who have sexual relations with other men in the context of vulnerability to HIV/AIDS. This was a cross-sectional, exploratory and descriptive study. It was carried out in a gay sociability place in Fortaleza, Ceará, Brazil, between November 2010 and March 2011, through interviews with 189 men who have sex with men. The ethical aspects were respected. We found a sample consisting mostly by young, single, and highly educated men. The sexual history demonstrated the early onset of sexual activity, with a high prevalence of sexual intercourse with a partner of the opposite sex. There was also a high prevalence of HIV testing. Sexual practices revealed high prevalence of performing oral and anal sex, as well as high levels of protection in anal sex, despite the low protection in oral sex. A greater incorporation of prevention practices was found compared to the national scene in the beginning of the disease outbreak.

El objetivo fue identificar los comportamientos y las prácticas sexuales de los hombres que tienen sexo con hombres en el contexto de la vulnerabilidad al VIH/SIDA. Fue un estudio transversal, descriptivo y exploratorio. Se celebró en una sociabilidad local gay de Fortaleza, Ceará, Brasil, entre noviembre de 2010 y marzo de 2011, a través de entrevistas con 189 hombres que tienen sexo con hombres. Se encontró una muestra compuesta en su mayoría por jóvenes, solteros y con alto nivel de educación. La historia sexual demostró el inicio temprano de la actividad sexual, la alta prevalencia de relaciones sexuales con una pareja del sexo opuesto. Hubo alta prevalencia de la prueba del VIH. Las prácticas sexuales revelaron una alta prevalencia de realizar sexo oral y anal, así como altos niveles de protección en el sexo anal, a pesar de la baja protección en el sexo oral. Se encontró una mayor incorporación de las prácticas de prevención en relación con la escena nacional en el inicio de la epidemia.

Hemodiálisis para remover el anticoagulante dabigatrán en situaciones de urgencia / Hemodialysis to remove anticoagulant dabigatran during emergencies

El dabigatrán es un nuevo inhibidor directo de la trombina, de administración oral, empleado para la prevención de eventos tromboembólicos en pacientes con fibrilación auricular no valvular. A diferencia de la warfarina, no se dispone de un antídoto conocido. La hemodiálisis ha sido sugerida como un método para remover el dabigatrán y reducir el efecto anticoagulante. Se presenta el caso de un paciente con antecedente de fibrilación auricular y medicado con dabigatrán, que fue admitido en el hospital para una cirugía abdominal de urgencia. A las seis horas de la última dosis recibida, los estudios de coagulación mostraban alteración. Ante la falta de antídoto para revertir los efectos, se decidió realizar hemodiálisis. Luego de tres horas de diálisis los parámetros de coagulación tendieron a normalizarse y el paciente fue operado sin presentar hemorragias anormales durante la cirugía o en el postoperatorio.

Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors, indicated for prevention of thromboembolic events in patients with non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known antidote. Hemodialysis has been suggested as a method for removing dabigatran and thereby reducing its anticoagulant effect. We report the case of a patient with a known history of atrial fibrillation, treated with dabigatran, who was admitted for emergency abdominal surgery. At six hours after the last dose received, coagulation studies were altered. In absence of an antidote to reverse its effects, it was decided to perform hemodialysis. After three hours of dialysis coagulation parameters were improved and the patient underwent surgery without showing abnormal bleeding during surgery or in the postoperative period.

New orally active anticoagulants in critical care and anesthesia practice: The good, the bad and the ugly.

With the adoption of dabigatran, rivaroxaban, and apixaban into clinical practice, a new era has arrived in the practice of oral anticoagulants. Venous thromboembolism (VTE) has traditionally been underdiagnosed and under treated in Asia. With increasing longevity, the diagnosis and the need for management of atrial fibrillation (AF) and VTE is likely to increase significantly. The new orally active anticoagulants (NOACs) have reasonably filled the lacunae that clinicians traditionally faced when treating patients with vitamin K antagonist (VKA). Unlike VKA, NOACs do not need frequent monitoring. Therefore, more patients are likely to get therapeutic effects of anticoagulation and thus reduce morbidity and mortality associated with VTE and AF. However, the clinicians need to be circumspect and exercise caution in use of these medications. In particular (in geriatric population), the clinicians should look out for drug-drug interactions and underlying renal insufficiency. This would ensure therapeutic efficacy and minimize bleeding complications. Here, it is important to note that the antidote for NOACs is not available and is a major concern if emergency surgical procedure is required in their presence.

Nuevos anticoagulantes orales en la prevención del ataque cerebrovascular / New oral anticoagulants in stroke prevention

Introduction: Atrial fibrillation (AF) is the most common arrhythmia. AF increases stroke risk by 5-fold and accounts for 15 percent of stroke. For more than 50 years, vitamin K antagonists were the only available oral anticoagulation. The two major classes of novel oral agents are direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban or rivaroxaban). These new agents require no routine laboratory monitoring and they are administered in a fixed dose. Method: A non systematic literature review was performed. Results: We performed a critical review of articles about new oral anticoagulants in stroke prevention. We evaluated properties of these agents and we compare efficacy and safety outcomes shown in clinical trials about new oral anticoagulants in AF. Discussion: New oral anticoagulants are at least as good as warfarin at preventing stroke in patients with AF. They seem to be safer than warfarin with significantly less intracranial bleeding. Trials demonstrate dabigatran to be the most effective in decreasing ischemic strokes, apixaban superior to warfarin with statistically lower mortality, and rivaroxaban no worse than warfarin for those with higher stroke risk. Conclussion: New oral anticoagulants have several advantages in comparison with warfarin, but we need further trials to know better the efficacy and safety of these new agents.

Introducción: La fibrilación auricular (FA) es la arritmia más frecuente, se asocia a un riesgo 5 veces mayor de ataque cerebrovascular (ACV), y da cuenta del 15 por ciento de los ACV isquémicos. Por más de medio siglo el tratamiento anticoagulante oral en FA ha estado limitado al uso de antagonistas de la vitamina K. Los nuevos anticoagulantes orales, se clasifican en dos categorías principales: inhibidores de la trombina como el dabigatrán y los inhibidores del factor Xa, como el apixabán y el rivaroxabán. Estos fármacos no requieren monitorización de los niveles de anticoagulación y se administran en dosis fija. Método: Revisión no sistemática de la literatura. Resultados: Se analizan de manera crítica los artículos sobre nuevos anticoagulantes orales en la prevención de ACV. Se evalúan las propiedades de estos nuevos agentes y se comparan los desenlaces de eficacia y de seguridad de los ensayos clínicos de los estos fármacos. Discusión: Los nuevos anticoagulantes orales son al menos tan efectivos que la warfarina en la prevención de ACV cardioembólico en pacientes con FA. Parecen ser más seguros con menor frecuencia de hemorragia intracranial. El dabigatrán es el más efectivo en disminuir el ACV isquémico, el apixabán es superior a la warfarina con una mortalidad significativamente inferior, y el rivaroxabán es no inferior a warfarina para pacientes con alto riesgo de ACV. Conclusión: Los nuevos anticoagulantes orales ofrecen varias ventajas en comparación a warfarina, sin embargo, se requiere se estudios adicionales para conocer más detalladamente su efectividad y perfil de seguridad.

Characterisation and starvation induced regulation of methionine uptake sites in mouse mammary gland.

The sites of methionine uptake by 10 day lactating mouse mammary gland were determined in vitro. Four modes of methionine entry characterised were: (i) A sodium-dependent, N-(methylamino) isobutyric acid (MeAIB)--sensitive system with a Vmax of 18.8 nmol/g cells/min (this mode of entry was similar to the A site in other tissues); (ii) A sodium-dependent, MeAIB--insensitive uptake system with a Vmax of 12.4 nmol/g cells/min); this mode of entry was inhibited by substrates preferred by ASC system); (iii) A sodium-independent, 2-amino-bicyclo heptane 2-carboxylic acid (BCH)-sensitive system L with a Vmax of 30 nmol/g cells/min; and (iv) A sodium-independent entry which was not inhibited by high concentrations of MeAIB or BCH. The Km value of each of the former three carrier mediated transport systems was 0.46 mM. Starvation of animals brought about important increase in the Vmax of the A system by 97% and that of ASC system by 1003% which was accompanied by similar increases in the Km values of these systems. These results show an adaptive regulation of these two sodium-dependent sites as a result of starvation.

Characterisation of the routes of methionine transport in mouse mammary glands.

The sites of methionine uptake by mammary glands from late pregnant and lactating mice were studied in vitro. Using the specific A system inhibitor, N-(methylamino) isobutyric acid (MeAIB) and the specific L system inhibitor, 2-amino-bicyclo (2.2.1) heptane 2-carboxylic acid (BCH), we have defined four modes of methionine entry into these tissues. (i) A sodium-dependent A system with a Vmax of 13.4 and 18.8 n mol/g cells/min in pregnant and lactating mice, respectively. This mode of entry was completely inhibited by MeAIB and its Km value was similar (0.45 mM) in both groups. (ii) A sodium-dependent mode with a Vmax of 6.7 and 12.4 n mol/g cells/min and a Km of 0.24 and 0.46 mM in pregnant and lactating mice, respectively. This mode of entry was insensitive to inhibition by MeAIB, and was similar to the ASC (alanine, serine, cysteine) system in other tissues. (iii) A sodium-independent L system with a Vmax of 13.8 and 30.0 n mol/g cells/min and a Km of 0.27 and 0.46 mM in pregnant and lactating mice, respectively. This mode of entry was completely inhibited by BCH. (iv) A sodium-independent non-specific entry amounting to 25 per cent of the total entry at 0.1 mM external methionine which was not inhibited by high concentration of BCH. The results of our studies show an increase in the number of active carriers of the A, ASC and L systems of methionine uptake in mammary glands of mouse during lactation.