RESUMO

Resumen La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

Abstract Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital´s reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

RESUMO

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

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Resumen El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la saludregión América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Abstract The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health OrganizationAmerican B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

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The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health Organization- American B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la salud- región América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

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Combined use of antiepileptic drugs and anticoagulants is common. We describe the first case documenting laboratory interaction between rivaroxaban and phenytoin. A 48-year-old woman was admitted to our hospital due to cerebral venous thrombosis, bilateral pulmonary embolism, and deep vein thrombosis. She came from a small town with difficult access to warfarin monitoring. She was receiving phenytoin 100 mg three times daily (t.i.d.) and started enoxaparin 60 mg twice daily (b.i.d.). An abdominal mass was diagnosed and removed by laparoscopy (gastrointestinal stromal tumor). On day 5, she was switched to rivaroxaban 15 mg b.i.d. First peak anti-Factor Xa was 70 ng/ml (reference value: 100-300 ng/ml). She was discharged on rivaroxaban 15 mg b.i.d. and phenytoin 100 mg t.i.d. A week later, anti-Xa levels were 90 ng/ml. Due to concerns about thrombosis progression, she was switched to dabigatran. During follow-up, she remained asymptomatic and thrombin time >180 s was measured several times along 3 months as surrogate for dabigatran activity. Phenytoin is a combined CYP3A4 and P-glycoprotein inducer, which might reduce rivaroxaban levels. Dabigatran is substrate of P-glycoprotein, meaning potential malabsorption. Despite unavailability of plasmatic dabigatran essays, our patient improved her symptoms without further symptomatic thromboembolism. Facing these interactions, either monitoring serum levels of anticoagulants or other therapeutic options should be considered.

RESUMO

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

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El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

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RESUMO

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

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La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

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RESUMO

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

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