None; None

Resúmenes

Objetivo: El Hospital Nacional de Geriatría y Gerontología (HNGG) maneja decenas de pacientes que reciben terapia de anticoagulación oral y que provienen de diferentes provincias del país; el estudio realizó una caracterización clínica y socio demográfica de la población adulta mayor anticoagulada que recibe control y tratamiento en la consulta externa de anticoagulados durante el periodo 2006-2007. Métodos: Se estudiaron 141 pacientes adultos mayores, anticoagulados con warfarina durante el periodo 2006-2007. Se realizó un análisis descriptivo de las características demográficas y clínicas de todos los pacientes enfatizando en causas de la anticoagulación, comorbilidades, cantidad de medicamentos utilizados, estado cognitivo, funcional y social, calidad de la anticoagulación, razones de suspensión del tratamiento y complicaciones. Resultados: El promedio de edad de los pacientes fue de 78 años. La mayor parte de la población proviene de los cantones Central, Desamparados y Escazú, todos pertenecientes a la provincia de San José y poseen un nivel académico bajo que no sobrepasa la escolaridad primaria. La fibrilación auricular fue el principal diagnóstico, que justificó la terapia de anticoagulación. La comorbilidad más importante fue la combinación entre la insuficiencia cardiaca y la hipertensión arterial. La mayor parte de la población utiliza cinco o más medicamentos sin tomar en cuenta la warfarina. El grupo de estudio en su mayoría presentó una capacidad cognitiva normal, una independencia funcional total o dependencia mínima y no presentaban riesgo social. Existió una alta variabilidad en el efecto terapéutico de la warfarina, reflejada en la dificultad de alcanzar niveles óptimos de INR en la mayor parte de las citas de control y en la cantidad de ajustes de tratamiento necesarios para mejorar la calidad de la misma. Las principales razones para suspender la terapia de anticoagulación fueron: mala adherencia al tratamiento, red social poco comprometida y efectos adversos relacionados con la sobre anticoagulación (sangrados menores). Hubo una incidencia similar de sangrados menores y mayores (4.3%) y una mortalidad del 1.4%. Conclusión: El manejo del paciente adulto mayor que recibe terapia de anticoagulación oral es de alta complejidad hecho que se ve reflejado tanto en su perfil demográfico como clínico. Las complicaciones asociadas a la terapia no difirieron con las reportadas a nivel internacional.El manejo del paciente adulto mayor que recibe terapia de anticoagulación oral es de alta complejidad hecho que se ve reflejado tanto en su perfil demográfico como clínico. Las complicaciones asociadas a la terapia no difirieron con las reportadas a nivel internacional.

anticoagulación; warfarina; sangrado; trombosis

Aim: The National Hospital of Geriatrics and Gerontology (HNGG), handles tens of patients which receives an oral anti-coagulation therapy and which come from diverse provinces of the country; the study realised a clinical and socio-demographic characterization of the anticoagulated older adult population, which receives control and treatment in the external consultation of anti-coagulated persons during the period 2006-2007. Methods:141 older adult patients were studied, all of them anti-coagulated with warfarin during the period 2006-2007. It was performed a descriptive analysis of the demographic and clinical characteristics of all the patients, making emphasis in the causes of the anti-coagulation, comorbitities, amount of medicines used, cognitive, functional and social status, quality of the anti-coagulation, reasons for the suspension of the treatment and complications. Results: The average of age of the patients was of 78 years. The larger part of the population come from the cantons of San Jose province, and possess a low academic level which does not surpass the primary schooling. The Auricular Fibrillation was the main diagnostic, which justifies the anti -coagulation therapy. The most important comorbidity was the combination between the Cardiac Insufficiency and the Arterial Hypertension. The larger part of the population uses 5 or more medicines apart from the warfarin. The group of study mainly presents an adequate cognitive status, a total functional independence or a minimal dependency, and they do not present a social risk. There was a high variability in the therapeutical effects of the warfarin, which reflects in the difficulty to reach optimal levels of INR in the larger part of the cites of control and in the amount of adjustments of treatment, necessary to improve the quality of same. The main reasons to suspend the therapy of anti-coagulation were the bad adherence to the treatment, a social network not involved and the adverse effects relationed with the over-anticoagulation (minor bleedings). There was a similar incidence of minor and major bleedings (4.3%), and mortality of 1.4%. Conclusion: The handling of the older adult patients which receive an oral anti-coagulation therapy is of high complexity, which is reflected both in its demographic as well as clinic profile. The complications associated to the therapy, do not differ to the ones reported to an international level.The handling of the older adult patients which receive an oral anti-coagulation therapy is of high complexity, which is reflected both in its demographic as well as clinic profile. The complications associated to the therapy, do not differ to the ones reported to an international level.

anti-coagulations; warfarin; bleeding; thrombosis

Aim: The National Hospital of Geriatrics and Gerontology (HNGG), handles tens of patients which receives an oral anti-coagulation therapy and which come from diverse provinces of the country; the study realised a clinical and socio-demographic characterization of the anticoagulated older adult population, which receives control and treatment in the external consultation of anti-coagulated persons during the period 2006-2007. Methods:141 older adult patients were studied, all of them anti-coagulated with warfarin during the period 2006-2007. It was performed a descriptive analysis of the demographic and clinical characteristics of all the patients, making emphasis in the causes of the anti-coagulation, comorbitities, amount of medicines used, cognitive, functional and social status, quality of the anti-coagulation, reasons for the suspension of the treatment and complications. Results: The average of age of the patients was of 78 years. The larger part of the population come from the cantons of San Jose province, and possess a low academic level which does not surpass the primary schooling. The Auricular Fibrillation was the main diagnostic, which justifies the anti -coagulation therapy. The most important comorbidity was the combination between the Cardiac Insufficiency and the Arterial Hypertension. The larger part of the population uses 5 or more medicines apart from the warfarin. The group of study mainly presents an adequate cognitive status, a total functional independence or a minimal dependency, and they do not present a social risk. There was a high variability in the therapeutical effects of the warfarin, which reflects in the difficulty to reach optimal levels of INR in the larger part of the cites of control and in the amount of adjustments of treatment, necessary to improve the quality of same. The main reasons to suspend the therapy of anti-coagulation were the bad adherence to the treatment, a social network not involved and the adverse effects relationed with the over-anticoagulation (minor bleedings). There was a similar incidence of minor and major bleedings (4.3%), and mortality of 1.4%. Conclusion: The handling of the older adult patients which receive an oral anti-coagulation therapy is of high complexity, which is reflected both in its demographic as well as clinic profile. The complications associated to the therapy, do not differ to the ones reported to an international level.

anti-coagulations; warfarin; bleeding; thrombosis

Original

Perfil clínico de los pacientes adultos mayores anticoagulados con warfarina del Hospital Nacional de Geriatría y Gerontología

(Clinical Profile of Elderly Patients on Anticoagulation Therapy with Warfarin)

Luis Alberto Laínez-Sánchez¹, Cynthia Villalobos-Masis²

*^{Correspondencia}

Resumen

Objetivo: El Hospital Nacional de Geriatría y Gerontología (HNGG) maneja decenas de pacientes que reciben terapia de anticoagulación oral y que provienen de diferentes provincias del país; el estudio realizó una caracterización clínica y socio demográfica de la población adulta mayor anticoagulada que recibe control y tratamiento en la consulta externa de anticoagulados durante el periodo 2006-2007.

Métodos: Se estudiaron 141 pacientes adultos mayores, anticoagulados con warfarina durante el periodo 2006-2007. Se realizó un análisis descriptivo de las características demográficas y clínicas de todos los pacientes enfatizando en causas de la anticoagulación, comorbilidades, cantidad de medicamentos utilizados, estado cognitivo, funcional y social, calidad de la anticoagulación, razones de suspensión del tratamiento y complicaciones.

Resultados: El promedio de edad de los pacientes fue de 78 años. La mayor parte de la población proviene de los cantones Central, Desamparados y Escazú, todos pertenecientes a la provincia de San José y poseen un nivel académico bajo que no sobrepasa la escolaridad primaria. La fibrilación auricular fue el principal diagnóstico, que justificó la terapia de anticoagulación. La comorbilidad más importante fue la combinación entre la insuficiencia cardiaca y la hipertensión arterial. La mayor parte de la población utiliza cinco o más medicamentos sin tomar en cuenta la warfarina. El grupo de estudio en su mayoría presentó una capacidad cognitiva normal, una independencia funcional total o dependencia mínima y no presentaban riesgo social. Existió una alta variabilidad en el efecto terapéutico de la warfarina, reflejada en la dificultad de alcanzar niveles óptimos de INR en la mayor parte de las citas de control y en la cantidad de ajustes de tratamiento necesarios para mejorar la calidad de la misma. Las principales razones para suspender la terapia de anticoagulación fueron: mala adherencia al tratamiento, red social poco comprometida y efectos adversos relacionados con la sobre anticoagulación (sangrados menores). Hubo una incidencia similar de sangrados menores y mayores (4.3%) y una mortalidad del 1.4%.

Conclusión: El manejo del paciente adulto mayor que recibe terapia de anticoagulación oral es de alta complejidad hecho que se ve reflejado tanto en su perfil demográfico como clínico. Las complicaciones asociadas a la terapia no difirieron con las reportadas a nivel internacional.

Descriptores: anticoagulación, warfarina, sangrado, trombosis

Abstract

Aim: The National Hospital of Geriatrics and Gerontology (HNGG), handles tens of patients which receives an oral anti-coagulation therapy and which come from diverse provinces of the country; the study realised a clinical and socio-demographic characterization of the anticoagulated older adult population, which receives control and treatment in the external consultation of anti-coagulated persons during the period 2006-2007.

Methods:141 older adult patients were studied, all of them anti-coagulated with warfarin during the period 2006-2007. It was performed a descriptive analysis of the demographic and clinical characteristics of all the patients, making emphasis in the causes of the anti-coagulation, comorbitities, amount of medicines used, cognitive, functional and social status, quality of the anti-coagulation, reasons for the suspension of the treatment and complications.

Results: The average of age of the patients was of 78 years. The larger part of the population come from the cantons of San Jose province, and possess a low academic level which does not surpass the primary schooling. The Auricular Fibrillation was the main diagnostic, which justifies the anti –coagulation therapy. The most important comorbidity was the combination between the Cardiac Insufficiency and the Arterial Hypertension. The larger part of the population uses 5 or more medicines apart from the warfarin. The group of study mainly presents an adequate cognitive status, a total functional independence or a minimal dependency, and they do not present a social risk. There was a high variability in the therapeutical effects of the warfarin, which reflects in the difficulty to reach optimal levels of INR in the larger part of the cites of control and in the amount of adjustments of treatment, necessary to improve the quality of same. The main reasons to suspend the therapy of anti-coagulation were the bad adherence to the treatment, a social network not involved and the adverse effects relationed with the over-anticoagulation (minor bleedings). There was a similar incidence of minor and major bleedings (4.3%), and mortality of 1.4%.

Conclusion: The handling of the older adult patients which receive an oral anti-coagulation therapy is of high complexity, which is reflected both in its demographic as well as clinic profile. The complications associated to the therapy, do not differ to the ones reported to an international level.

Keywords: anti-coagulations, warfarin, bleeding, thrombosis

El envejecimiento es considerado un factor de riesgo cardiovascular mayor. Las enfermedades cardiacas son la causa más común de muerte en los ancianos.¹Debido al incremento de la longevidad y la disminución de la fertilidad, la población geriátrica se ha incrementado considerablemente en países industrializados. Para el 2020, se espera que la población mayor de 80 años pase de 3.7% a 7.5%.²

La terapia de anticoagulación representa uno de los principales tratamientos en pacientes mayores con cardiopatías. Los beneficios de esta terapia en esta población están demostrados, sin embargo es este mismo grupo el más vulnerable a presentar efectos adversos. Esto podría estar potenciado por la presencia de enfermedades con un potencial trombo embólico elevado, como la fibrilación auricular. ³-⁶

Diversos factores propios de la población mayor hacen que la terapia de anticoagulación sea compleja. Entre ellos destacan: la alteración de la homeostasis asociada al envejecimiento, caracterizada por un incremento en la actividad plaquetaria,⁷,⁸la estasis sanguínea y la degeneración de la pared vascular con disfunción endotelial.⁹Los aspectos farmacocinéticos y farmacodinámicos relacionados con la absorción, distribución, metabolismo y aclaramiento de drogas antitrombóticas, deben ser considerados cuando se inicie terapia de anticoagulación. La polifarmacia, fenómeno propio de la población geriátrica, genera un mayor riesgo de efectos adversos por interacciones droga-droga.¹⁰

Actualmente no hay consenso general en la definición de adulto mayor, por lo que generalizar los hallazgos de diferentes estudios es problemático. Frecuentemente la población mayor es excluida de estudios clínicos cardiovasculares, de tal forma que los tratamientos actuales se han desarrollado con base en poblaciones más jóvenes. Esta es una de las razones por la cual la terapia de anticoagulación es infrautilizada en el paciente adulto mayor.¹¹-¹³

En general el tratamiento con anticoagulantes orales, esta asociado a un 0.3% a 0.5% de riesgo anual de sangrados mayores.¹⁴Hay una tendencia al incremento de sangrados menores y hemorragia intracraneal en los ancianos de 2 a 3 veces.¹⁴,¹⁵Esta es otra importante razón por la que los médicos tienden a infrautilizar este tratamiento, debido al elevado riesgo de sangrados y caídas, que pueden provocar complicaciones hemorrágicas serias.¹⁶Las dosis para mantener rangos adecuados de INR en personas mayores de 60 años disminuye con la edad, posiblemente por la reducción del aclaramiento de estos fármacos con el envejecimiento. Por tanto, debe ser tomado en consideración siempre que se inicie terapia de anticoagulación.¹⁷,¹⁸

El Hospital Nacional de Geriatría y Gerontología brinda atención a un número importante de pacientes que reciben terapia de anticoagulación oral y que provienen de diferentes provincias del país. En este estudio se analizó la información general de un grupo de pacientes anti coagulados con warfarina, atendidos en el HNGG, con el objetivo de conocer el perfil clínico y sociodemográfico de esta población.

Materiales y métodos

Se realizó un estudio observacional descriptivo de la totalidad de pacientes anti coagulados con warfarina, que seguían control en la consulta externa del HNGG, desde el 1 de enero del 2006 al 31 de diciembre del 2007. El análisis realizado fue retrospectivo, utilizando la información de los expedientes clínicos de cada paciente. La investigación recibió el aval del Comité de Ética en Investigación del Hospital Nacional de Geriatría y Gerontología y no requirió de Consentimiento Informado, ya que se trató de un estudio no intervencionista, manteniendo la confidencialidad de los sujetos incluidos en la investigación.

Se obtuvo una muestra de 141 pacientes anti coagulados con warfarina, entre el 1 de enero del 2006 y el 31 de diciembre del 2007, los cuales eran atendidos periódicamente en la consulta externa del HNGG. Se definieron las siguientes variables: edad, género, procedencia, nivel educativo, motivo de anticoagulación, comorbilidades, polifarmacia (uso de 5 o más medicamentos), estado cognitivo (para su valoración se utilizó la escala para detección de deterioro cognitivo Mini Mental State Examination - MMSE),¹⁹estado funcional (para su valoración se utilizó la escala de Actividades Básicas de Vida Diaria - BARTHEL),²⁰riesgo social (se consideró cuando existía mala adherencia al tratamiento, red familiar poco comprometida en el control del paciente e institucionalización), número de citas control, promedio de ajustes de tratamiento (número de ajustes en las dosis de warfarina ya sea en aumento o disminución con respecto a las citas control), calidad de la terapia de anticoagulación (se valoró según niveles de Índice Normalizado Internacional – INR: óptimo 2-3, sub terapéutico <2 y supra terapéutico >3, dosis utilizada de warfarina, razones de suspensión de tratamiento (de índole médico, psíquico, funcional y social) y complicaciones.

El criterio de inclusión comprendía los pacientes anti coagulados con warfarina, en control y seguimiento en la consulta externa del HNGG entre el 1 de enero del 2006 y el 31 de diciembre del 2007. Los criterios de exclusión utilizados fueron: pacientes controlados con otro tipo de terapia anticoagulante diferente a warfarina e información incompleta en los expediente clínicos.

Se hicieron distribuciones de frecuencias absolutas y relativas de todas las variables, para las variables cuantitativas se obtuvo el promedio, la mediana y la desviación estándar.

Para determinar el número de pacientes que alcanzaron niveles adecuados de anticoagulación, se definió como “nivel aceptable de normalidad”, el haber tenido niveles óptimos de INR (2-3) al menos en el 50% de las citas a las que acudió en el período analizado.

Para las variables diagnóstico, tipo de complicación, polifarmacia, comorbilidades, dosis utilizada de warfarina, capacidad cognitiva, capacidad funcional y riesgo social se realizaron comparaciones por edad y género de los pacientes. Los resultados de las comparaciones de estas variables se sometieron a pruebas de significancia estadística.

Para las variables cualitativas se aplicó el Chi-Cuadrado, para las cuantitativas se utilizó la prueba t de student o el análisis de variancias dependiendo del número de grupos a comparar. Cuando el análisis de variancia resultó estadísticamente significativo se realizaron los post test de Bonferroni y Tukey para identificar los grupos que mostraron diferencias.

Se realizó una correlación de Pearson con las variables cuantitativas número de consultas y ajustes de tratamiento. La información se resumió en cuadros y gráficos. En ambos análisis se considera significativo a un nivel de confianza <0,05. La información fue transferida a una base de datos y procesada en el paquete estadístico SPSS versión 13 y Excel para la elaboración de gráficos.

Resultados

La población global del estudio (N=141) tuvo una distribución por sexo similar, con un promedio de edad de 78.3 años, desviación estándar (DE) de 7.4 años, mediana de 78 años.

La mayoría provenían de la provincia de San José (Cantón Central 34.2%, Desamparados 22.2% y Escazú 10.3%) y poseían un nivel académico bajo que no sobrepasó la escolaridad primaria 74.5%.

La fibrilación auricular fue el principal diagnóstico, para la indicación de la terapia de anticoagulación 61% (Figura 1). La combinación de insuficiencia cardiaca e hipertensión arterial fueron las comorbilidades más prevalentes 37.6%.

La mayor parte de la población utilizó 5 o más medicamentos sin tomar en cuenta la warfarina 80.9% (^{Cuadro 1}).

Los casos analizados presentaron una capacidad cognitiva adecuada 72.3% , una independencia funcional total o dependencia funcional mínima 85.8% y no presentaron factores de riesgo social 85.1%.

Se logró determinar que el 42.6% de los pacientes tuvo niveles aceptables de INR, no se encontraron diferencias estadísticamente significativas entre hombres y mujeres p=0.78 (^{Cuadro 2}). En el grupo de pacientes que presentaron una calidad de anticoagulación no aceptable, los niveles de INR fueron variables desde la sub anticoagulación hasta la sobre anticoagulación en un mismo caso, por lo que la subdivisión de este último grupo no se pudo establecer.

La dosis promedio de warfarina utilizada por los pacientes que alcanzaron niveles óptimos de INR en la mayoría de sus consultas fue de 3.7 mg por día; mientras que en el grupo que no alcanzó nivelesóptimos de anticoagulación la dosis promedio fue de 3.5 mg por día, sin encontrar diferencia estadísticamente significativa (p=0.55).

Existió una alta variabilidad en el efecto terapéutico de la warfarina, lo cual se reflejó, en la dificultad de alcanzar niveles óptimos de INR en la mayor parte de las citas de control y en la cantidad de ajustes de tratamiento necesarios para optimizar la misma (r2=0.89, p=0.00).

Las principales razones para suspender la terapia de anticoagulación fueron la mala adherencia al tratamiento, pobre supervisión familiar en el control del paciente y los efectos adversos relacionados con la sobre anticoagulación -sangrados menores.

Hubo una incidencia similar de sangrados menores y mayores 4.3%, estos últimos se distribuyeron en sangrados del sistema nervioso central y hematomas retroperitoneales. Hubo una mortalidad del 1.4% y no se documentaron eventos trombóticos asociados a niveles subterapéuticos de anticoagulación, ni casos de necrosis de piel secundaria al uso de warfarina (^{Cuadro 3}).

Discusión

El perfil clínico de los adultos mayores que recibieron terapia de anticoagulación oral con warfarina analizados en este estudio es de alta complejidad. Esto se refleja en sus características tanto sociodemográficas como clínicas.

Con el envejecimiento, el riesgo de sufrir enfermedades con alto potencial trombo embólico se incrementa considerablemente. Una de las patologías que demuestra este hecho es la fibrilación auricular. Este trastorno del ritmo crece a medida que la población envejece y su asociación con embolismo cerebral se potencia; como lo demostró el estudio de Framingham, donde la población mayor presentó 5.6 veces más riesgo de desarrollar esta asociación.³,⁴Tal y como se demuestra en este estudio, la principal causa de anticoagulación fue la fibrilación auricular, lo cual es compatible con la literatura.

Diversos factores propios de la población mayor hacen que la terapia anticoagulante sea compleja. Dentro de ellos destacan factores biológicos y farmacológicos que dificultan la obtención de niveles adecuados de anticoagulación y pueden generar efectos adversos por interacciones no deseadas.⁷Los adultos mayores que recibieron terapia anticoagulante en este estudio presentaron 2 características particulares: la presencia de múltiples comorbilidades, fundamentalmente de tipo cardiovascular y polifarmacia. Es importante enfatizar en estos factores cuando se va iniciar terapia de anticoagulación oral con warfarina en el anciano, para tratar de reducir las complicaciones asociadas al tratamiento, ya que el envejecimiento pos sí solo confiere un incremento en la actividad plaquetaria, estasis sanguínea y degeneración de pared vascular con disfunción endotelial.⁸,⁹

La valoración integral de los pacientes mayores incluye la evaluación de 4 áreas fundamentales: médica, psíquica, funcional y social. Existe poca evidencia sobre el papel de la integridad psíquica, funcional y social del paciente mayor con relación a la terapia de anticoagulación, sin embargo los estudios existentes han demostrado una mayor tasa de complicaciones en aquellos pacientes con deterioro de su capacidad cognitiva, limitación funcional importante y riesgo social.²²,²³En la mayor parte de los pacientes estudiados se logró demostrar de una manera objetiva (a través de instrumentos validados), una capacidad cognitiva, funcional y un entorno social adecuado. En términos de riesgo-beneficio es importante considerar estos factores integralmente al momento de seleccionar a un paciente candidato a terapia de anticoagulación oral. La valoración cuadrifuncional (médica, psíquica, funcional y social) es una herramienta importante para decidir si el paciente es apto para tratamiento crónico anticoagulante o para un manejo más conservador.²¹

Con relación a la calidad de la anticoagulación, los resultados demuestran que no se alcanzaron niveles óptimos de INR en la mayor parte de los pacientes estudiados, fenómeno que tiene una base multifactorial. Lo anterior se demostró al analizar la respuesta terapéutica de la warfarina tanto en los pacientes que alcanzaron niveles óptimos de INR, como aquellos que no lo alcanzaron. Apesar que ambos grupos utilizaron dosis (mg) similares de medicamento, la respuesta terapéutica difirió entre un paciente y otro. Esta variabilidad individual justificó una mayor de cantidad de citas control en diferentes pacientes, debido a los ajustes de dosis efectuados para tratar de optimizar la anticoagulación.

Un aspecto importante del estudio, es que existieron casos en los cuales valorando el riesgo-beneficio del tratamiento se decidió suspender la terapia de anticoagulación. Las razones más importantes de suspensión de terapia en el grupo de estudio fueron de índole social y médico. Llama la atención que aunque el porcentaje de suspensión de tratamiento fue bajo, la falta de supervisión familiar, en relación a la adherencia de la medicación fue el factor más importante para suspender la medicación. Esto debido a que la warfarina posee un perfil de seguridad reducido y es un fármaco que se debe controlar periódicamente; de tal forma que el paciente mayor necesita de apoyo y supervisión para obtener resultados óptimos en su terapia y evitar complicaciones asociadas a la misma.²⁴,²⁵Por tanto, la valoración del entorno social es un requisito indispensable previo al inicio de terapia crónica con warfarina en el anciano.

A mayor edad el riesgo de complicaciones asociado a la terapia de ACO aumenta considerablemente, sin embargo si esta terapia se realiza de una manera integral, las complicaciones no difieren de forma significativa al compararlas con otros grupos etareos y el beneficio obtenido en términos de prevención secundaria es mayor que el obtenido en poblaciones más jóvenes. El comportamiento de las complicaciones para este estudio, tanto para los eventos hemorrágicos mayores y menores fue similar al descrito en la literatura,¹⁴,¹⁵y la mortalidad asociada a la terapia muy cercana a la establecida en diferentes investigaciones.¹⁶

Dentro de las limitaciones del estudio cabe mencionar el tipo de diseño del mismo. Al ser este un estudio descriptivo basado en la recopilación de datos de expedientes clínicos en la consulta de anticoagulación, se puede omitir información importante con relación a la terapia en notas de servicios de emergencia y hospitalización. En relación con el análisis estadístico de las variables, la calidad de la anticoagulación fue difícil de obtener, ya que por la variabilidad multifactorial de la respuesta al tratamiento la mayor parte de los pacientes en algún momento presentaron niveles óptimos de anticoagulación, subanticoagulación y sobre anticoagulación durante sus citas control. Por esta razón se agruparon a los pacientes en aquellos que tuvieron niveles aceptables y no aceptables por clasificación personal del autor ya que esta no tiene respaldo en la literatura internacional.

En vista de la complejidad del paciente adulto mayor que recibe terapia de anticoagulación oral, es necesario implementar un enfoque de manejo interdisciplinario, el cual debe incluir la formación de clínicas de anticoagulación donde se fomente la participación de diferentes especialistas en salud, se efectué un monitoreo cercano del paciente y donde se involucre en el manejo tanto al paciente como a sus familiares.

Referencias

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5. Hyleck EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96.
6. The Stroke Prevention in Atrial Fibrillation Investigators. Bleeding during antithrombotic therapy in patients with atrial fibrillation. Arch Intern Med 1996; 156: 409–16.
7. Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol 2006; 60: 144–51.
8. Bastyr EJ 3rd, Kadrofske MM, Vinik AI. Platelet activity and phosphoinositide turnover increase with advancing age. Am J Med 1990; 88: 601–6.
9. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res 2005; 66: 286–94.
10. Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol 2003; 38: 843–53.
11. Skolnick AH, Alexander KP, Chen AY. Characteristics, management, and outcomes of 5,557 patients age > or = 90 years with acute coronary syndromes: results from the CRUSADE Initiative. J Am Coll Cardiol 2007; 49: 1790–7.
12. GRACE Investigators. Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J 2001; 141: 190–9.
13. Alexander KP, Chen AY, Roe MT. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA 2005; 294: 3108–16.
14. Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic complications of anticoagulant and thrombolytic treatment. Chest 2008; 133: 257S–98S.
15. Hyleck EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96.
16. Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005; 118: 612–7.
17. Garcia D, Regan S, Crowther M. Warfarin maintenance dosing patterns in clinical practice. Chest 2005; 127: 2049–56.
18. Klein TE, Altman RB, Eriksson N. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360: 753–764.
19. Crum RM, Anthony JC, Bassett SS and Folstein MF. Population-based norms for the mini-mental state examination by age and educational level. JAMA. 1993; 18: 2386-2391.
20. J A Mirallas Martinez. M^aC Real Collado. Indice de Barthel o Medida de independencia functional. Rehabilitación (Madr). 2003; 37: 152-7.
21. Bellelli G, Bianchetti A, Trabucchi M. Anticoagulation to prevent stroke in atrial fibrillation: comprehensive geriatric evaluation should be routine before treatment is started [letter]. BMJ 2000; 321: 1157.
22. Palareti G, Poggi M, Guazzaloca G, Savino A, Coccheri S. Assessment of mental ability in elderly anticoagulated patients: its reduction is associated with a less satisfactory quality of treatment. Blood Coagul Fibrinolysis 1997; 8: 411-417.
23. Bellelli G, Guerini F, Bianchetti A, Trabucchi M. Anticoagulation in disabled patients [letter]. Arch Intern Med 2002; 162: 107-108.
24. Beyth RJ, Quinn L, Landefeld CS. A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin: a randomized, controlled trial. Ann Intern Med 2000; 133: 687-695.
25. Tang EO, Lai CS, Lee KK, Wong RS, Cheng G, Chan TY. Relationship between patients’ warfarin knowledge and anticoagulation control. Ann Pharmacother. 2003; 37: 34-39.

^*1 Médico especialista en Geriatría y Gerontología, Hospital San Rafael de Alajuela

^*2 Médico especialista en Geriatría y Gerontología, Hospital Nacional de Geriatría y Gerontología

Nombre de departamento: Hospital Nacional de Geriatría y Gerontología Consulta Externa de Anticoagulados

Abreviaturas: ACO: Anticoagulación oral;BARTHEL, Test de valoración funcional de actividades básicas de vida diaria. HNGG, Hospital Nacional de Geriatría y Gerontología; Mg, Miligramos; INR, Índice Normalizado Internacional; MMSE, Mini Mental State Examination - Test de tamizaje para Deterioro Cognitivo.

^*Correspondencia a: Luis Alberto Laínez Sánchez

Correo electrónico: luislainez69@gmail.com

Recibido: 12 de julio de 2010 Aceptado: 30 de junio de 2011

en_aart4.htm

Original

Clinical Profile of Elderly Patients on Anticoagulation Therapy with Warfarin

Luis Alberto Laínez-Sánchez ¹ , Cynthia Villalobos-Masis ²

^{*Contact information}

Abstract

Aim: The National Geriatrics and Gerontology Hospital (HNGG) handles tens of patients which receive oral anticoagulation therapy and which come from different provinces of the country; the study did a clinical and socio-demographic characterization of the anticoagulated elderly population that receives control and treatment in the outpatient consultation clinic for anticoagulation patients during the period 2006-2007.
Methods: 141 elderly patients that received anticoagulation therapy with warfarin during the period 2006-2007 were studied. A descriptive analysis of the demographic and clinical characteristics of all the patients was performed, emphasizing on the causes of anticoagulation, comorbidities, number of drugs used; cognitive, functional and social status, quality of the anticoagulation, reasons for suspension of the treatment and complications.
Results: The average age of the patients was of 78 years. Most of the population comes from the Central, Desamparados and Escazú cantons of the Province of San Jose and have a low academic level, which does not surpass primary schooling. Atrial fibrillation was the main diagnostic, which justified the anticoagulation therapy. The most important comorbidity was the combination between heart failure and hypertension. Most of the population uses 5 or more drugs apart from warfarin. The majority of the individuals in the group studied showed an adequate cognitive status, total functional independence or a minimum dependency, and they did not show a social risk. There was a high variability in the therapeutical effects of warfarin, which was reflected in the difficulty to reach optimal levels of INR in a large part of the control consultations and in the amount of treatment adjustments necessary to improve its quality. The main reasons to suspend the anticoagulation therapy were bad adherence to treatment, a poorly committed social network and the adverse effects related to over anticoagulation (minor bleedings). There was a similar incidence of minor and major bleedings (4.3%), and a mortality of 1.4%.
Conclusion: The handling of elderly patients that receive oral anticoagulation therapy is highly comple, an aspect that is reflected both in its demographic as well as clinic profile. The complications associated to the therapy, did not differ from the ones reported at an international level.

Key words: anticoagulation, warfarin, bleeding, thrombosis.

Aging is considered a major cardiovascular risk factor. Heart diseases are the most common cause of death among the elderly.¹ Due to increased longevity and declining fertility, the geriatric population has considerably increased in industrialized countries. By 2020, the population age 80 years and above is expected to rise from 3.7% to 7.5%.²

Anticoagulation therapy is one of the main treatments in elderly patients with heart disease. The benefits of this therapy in said population are well established, however, it is the most vulnerable group to adverse effects. This could be further exacerbated by the presence of diseases at high risk for thromboembolism potential, such as atrial fibrillation.^3-6

Several factors inherent to the elderly population add complexity to anticoagulation therapy. Among these factors, the following stand out: age-dependent alterations of homeostasis, characterized by increased platelet activity, ⁷.⁸ blood stasis, and vessel wall degeneration with endothelial dysfunction.⁹ The pharmacokinetic and pharmacodynamic aspects related to the absorption, distribution, metabolism and clearance of antithrombotic drugs must be considered when commencing anticoagulation therapy. Polypharmacy, a common phenomenon in the geriatric population, generates a greater risk of adverse drug-drug interactions.¹⁰

Currently, there is no general consensus about the definition of elderly; therefore, to generalize the findings of different studies is problematic. The elderly population is frequently excluded from cardiovascular clinical trials, therefore current treatments have been developed on the basis of younger populations. This is one of the reasons for the underutilization of anticoagulation therapy in elderly patients.^11-13

In general, treatment with oral anticoagulants is associated with a 0.3% to 0.5% of major bleeding per year.¹⁴ There is a tendency towards a 2- to 3-fold increase in minor bleeding and intracranial haemorrhages among elderly patients.¹⁴, ¹⁵ This is another important reason that explains physicians’ tendency to underutilize this treatment due to the high risk of bleeding and falls, which can cause serious hemorrhagic complications.¹⁶

The doses required to maintain adequate INR ranges in patients over 60 years of age decreases with increasing age, possibly due to the reduction in the clearance of these drugs with ageing. Therefore, it should be taken into consideration whenever anticoagulation therapy commences.¹⁷, ¹⁸

The Hospital Nacional de Geriatría and Gerontología [National Geriatrics and Gerontology Hospital] provides medical care to a significant number of patients that receive oral anticoagulation therapy and who come from different provinces in the country. In this study, the general information of a group of patients that received anticoagulation therapy with warfarin at the HNGG was analysed, in order to determine the clinical and sociodemographic profile of this population.

Materials and methods

An observational- descriptive study was carried out about the total number of patients that received anticoagulation therapy with warfarin, who attended outpatient control consultation at the HNGG, from January 1, 2006 to December 31, 2007. The analysis performed was retrospective, using the information in each patient’s medical records. Research was approved by the Comité de Ética en Investigación del Hospital Nacional de Geriatría y Gerontología [HNGG Research Ethics Committee] and it did not require informed consent because it was a non- interventional study that safeguarded the confidentiality of the subjects included.

A sample was obtained of 141 patients that received anticoagulation therapy with warfarin between January 1, 2006 and December 31, 2007 and who received periodical outpatient consultation attention at the HNGG. The following variables were determined: age, sex, origin, education level, reason for anticoagulation, comorbidities, polypharmacy (use of 5 or more drugs), cognitive status (for its assessment, the Mini Mental State Examination for cognitive impairment detection- MMSE- was used), ¹⁹ functional status (for its assessment, the Basic Activities of Daily Living Index – BARTHEL- was used), 20 social risk (the factors considered were: poor adherence to treatment, low commitment of family network with the patient’s monitoring and institutionalization), number of control appointments, average number of treatment adjustments (number of adjustments in the warfarin dose, either increase or decrease as a result of control appointments), quality of the anticoagulation therapy (assessed according to International Normalised Ratio- INR- levels: optimal 3), warfarin dose used, reasons for suspension of>2 and supra therapeutic <2-3, sub therapeutic treatment (medical, psychological, functional and social), and complications.

The inclusion criteria comprised the patients that received anticoagulation therapy with warfarin, under control and monitored at the HNGG outpatient consultation between January 1, 2006 and December 31, 2007. The exclusion criteria used were: patients treated with other therapies different from warfarin and incomplete information in the medical records.
Absolute and relative frequency distributions were calculated for all variables; for quantitative variables, the mean, median and standard deviation values were found.

To determine the number of patients that achieved adequate levels of anticoagulation, the "acceptable level of normality” was defined by obtaining optimal levels of INR (2-3) in at least 50% of the appointments attended during the analyzed period.
Comparisons according to age and sex of patients were made for diagnostic variables, type of complication, polypharmacy, comorbidities, warfarin dose used, cognitive ability, functional ability and social risk. The results obtained from the comparison of these variables were tested for statistical significance.

For qualitative variables, chi-square was applied; for the quantitative ones, the student t test or variance analysis was used, depending on the number of groups to be compared. When the variance analysis was found to be statistically significant, the Bonferroni and Tukey post-tests were performed to identify the groups that showed differences.

A Pearson correlation was performed using the quantitative variables number of consultations and treatment adjustments. The information was summarized in tables and graphs. In both analyses, significance is considered at a confidence level of <0.05. The information was transferred to a database and processed using the SPSS statistical programme version 13 and Excel, in order to make charts.

Results

The study’s overall population (N=141) had a similar distribution per sex, an average age of 78.3 years, standard deviation (SD) of 7.4 years, median, 78 years.
A majority of the patients came from the province of San José (Central Canton 34.2%, Desamparados 22.2% and Escazú10.3%) and 74.5% had a low academic level that did not exceed primary school education.

Atrial fibrillation was the main diagnosis for prescription of anticoagulation therapy 61% (Figure 1). The combination of heart failure and hypertension were the most prevalent comorbidities, 37.6%.

Apart from warfarin, the majority of the population used 5 or more drugs 80.9% (Table 1).

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The analyzed cases showed an adequate cognitive capacity 72.3%, total functional independence or minimum functional dependence 85.8% and did not show social risk factors 85.1%.

It was determined that 42.6% of patients had acceptable levels of INR, no statistically significant differences between men and women were found, p=0.78 (Table 2). In the group of patients who showed an unacceptable quality of anticoagulation, INR ranges varied from under-anticoagulation to over-anticoagulation in a same case, thus, the subdivision of the latter group could not be established.

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The average warfarin dose used by patients who achieved optimal INR levels in most of their consultation visits was 3.7 mg per day; while in the group that did not reach optimal levels of anticoagulation the average dose was 3.5 mg per day, no statistically significant difference was found (p=0.55).

There was a high variability in the therapeutic effect of warfarin. This was reflected in the difficulty to achieve optimal levels of INR in most of the control appointments and in the number of necessary adjustments to the amount of treatment required to optimize it (r2=0.89, p=0.00).

The main reasons to suspend anticoagulation therapy were bad adherence to treatment, poor family supervision in the patient’s monitoring and adverse effects associated to anticoagulation, such as minor bleeding.

There was a similar incidence of minor and major bleeding 4.3%, the latter were distributed in central nervous system bleeding and retroperitoneal haematomas. The mortality rate was 1.4% and no thrombotic events associated with subtherapeutic levels of anticoagulation were registered nor cases of skin necrosis secondary to the use of warfarin (Table 3).

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Discussion

The clinical profile analyzed in this study, of elderly patients who received oral anticoagulation therapy with warfarin, is highly complex. This is reflected in both, their sociodemographic and clinical characteristics.

With aging, the risk of suffering from diseases with high potential for thromboembolism increases significantly. Atrial fibrillation is one of the pathologies that evidences this fact. This disorder in cardiac rhythm increases as the population ages and its association with cerebral embolism is enhanced; as demonstrated by Framingham’s study, where the population showed 5.6 times greater risk of developing this asociación.³, ⁴ As shown in this study, the main cause of anticoagulation was atrial fibrillation; all of which is consistent with the literature.
Several factors inherent to the elderly population make anticoagulant therapy a complex one. Among them, biological and pharmacological factors stand out, as they challenge the attainment of adequate levels of anticoagulation and can generate adverse effects due to undesirable interactions.⁷Elderly patients who received anticoagulation therapy in this study showed two particular characteristics: the presence of multiple comorbidities, mainly of a cardiovascular type, and polypharmacy. It is important to pay close attention to these factors when commencing oral anticoagulation therapy with warfarin in elderly patients, in order to endeavour to reduce the complications associated to treatment, as aging by itself entails an increase in platelet activity, blood stasis and vessel wall degeneration with of endothelial dysfunction.⁸, ⁹

The comprehensive assessment of elderly patients includes the assessment of 4 key areas: medical, psychological, functional and social. There is scant evidence on the role of mental, functional and social integrity on the elderly patient with regard to anticoagulation therapy, however existing studies have shown a higher rate of complications in those patients with impaired cognitive ability, significant functional limitations and at social risk.²², ²³ It was possible to establish for most of the patients studied, in an objective manner (through validated instruments), an appropriate cognitive ability, functional status and social environment. In terms of risk-benefit analysis, it is important to consider these factors in an integral manner when selecting a patient as a candidate for oral anticoagulation therapy. A assessment of the four functions (medical, psychological, functional and social) is an important tool to decide whether the patient is suitable for chronic anticoagulant treatment or for a more conservative management.²¹

With regard to the quality of anticoagulation, the results show that optimal INR levels were not obtained from the majority of the patients studied, a phenomenon that has a multi-factor basis. This was demonstrated by analyzing the warfarin’s therapeutic response in both, patients who reached optimal levels of INR and in those who did not reach them. Although both groups used similar drug doses (mg), the therapeutic response was different from one patient to another. This individual variability justified a greater amount of control appointments in different patients due to dose adjustments prescribed to try to optimize anticoagulation.

An important aspect of the study is that there were cases in which assessment of the treatment’s risk-benefit led to the decision to suspend anticoagulation therapy. The most important reasons for the suspension of therapy in the study group were of a social and medical character.

It is noteworthy that, although the percentage of treatment suspension was low, lack of family monitoring in relation to medication adherence was the most important factor influencing the suspension of medication. This occurs because warfarin has a low safety profile and is a drug that should be monitored periodically; therefore the elderly patient requires support and supervision in order to obtain optimal results in its therapy and to prevent associated complications.²⁴,²⁵ Therefore, assessment of the social environment is a prerequisite prior to commencing chronic warfarin therapy in the elderly.

The risk of complications associated with OAC therapy significantly rises with increasing age, however if this therapy is practised in a comprehensive manner, the complications do not differ significantly when compared with other age groups and the benefit in terms of secondary prevention is greater than that obtained in younger populations. The behaviour of complications in this study for both, major and minor bleeding events, was similar to that described by the literature,¹⁴,¹⁵ and mortality associated to this therapy was very close to that established in different reports.¹⁶

Within the study’s limitations, it is worth mentioning its type of design. Since this is a descriptive study, based on data collection from medical records in the anticoagulation outpatient consultation, important information about the therapy from the emergency and hospitalization services’ notes could have been omitted. Regarding the statistical analysis of the variables, the quality of anticoagulation was difficult to obtain; because of the multi-factor variability response to treatment, most patients showed at some point during their monitoring appointments optimal levels of anticoagulation, under-coagulation and over- coagulation. For this reason, patients were grouped into those who had acceptable and unacceptable levels as a result of the author's personal criteria, as this classification is not supported by international literature.

Given the complexity of administering oral anticoagulation therapy to elderly patients, it is necessary to implement an interdisciplinary management approach, which should include the establishment of anticoagulation clinics that promote the participation of different health specialists, conduct a close monitoring of the patient and that involve in its management both, the patient and its family.
References

en_art4()

¹. Specialist in Geriatrics and Gerontology, Hospital San Rafael de Alajuela [San Rafael de Alajuela Hospital.]

². Specialist in Geriatrics and Gerontology, Hospital Nacional de Geriatría y Gerontología [National Geriatrics and Gerontology Hospital]

Name of the department: Hospital Nacional de Geriatría y Gerontología

Anticoagulants Outpatient Consultation

^*Contact information:

Luis Alberto Laínez Sánchez

Email address: luislainez69@gmail.com

Abbreviations: ACO: oral anticoagulation; BARTHEL, Barthel's Index of Activities of Daily Living. HNGG, Hospital Nacional de Geriatría y Gerontología; Mg, milligrams; INR, International Normalized Ratio; MMSE, Mini Mental State Examination.

Received: July 12, 2010 Accepted: June 30, 2011

Fechas de Publicación

Publicación en esta colección
08 Feb 2012
Fecha del número
Dic 2011

Histórico

Recibido
12 Jul 2010
Acepto
30 Jun 2011

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[2] 2. Anderson GF, Hussey PS. Population aging: a comparison among industrialized countries. Health Aff 2000; 19: 191–203.

[3] 3. Alan S. Go MD; Elaine M. Hylek, MD, MPH; Kathleen A. Phillips, BA; YuChiao Chang, PhD; Lori E. Henault, MPH; Joe V. Selby, MD, MPH; Daniel E. Singer, MD. Prevalence of diagnosed atrial fibrillation in adults: National implications for rhythm management and stroke prevention: the anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-2375.

[4] 4. Goto S, Bhatt DL, Röther J. Prevalence, clinical profile, and cardio- vascular outcomes of atrial fibrillation patients with atherothrombosis. Am Heart J 2008; 156: 855–63.

[5] 5. Hyleck EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96.

[6] 6. The Stroke Prevention in Atrial Fibrillation Investigators. Bleeding during antithrombotic therapy in patients with atrial fibrillation. Arch Intern Med 1996; 156: 409–16.

[7] 7. Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol 2006; 60: 144–51.

[8] 8. Bastyr EJ 3rd, Kadrofske MM, Vinik AI. Platelet activity and phosphoinositide turnover increase with advancing age. Am J Med 1990; 88: 601–6.

[9] 9. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res 2005; 66: 286–94.

[10] 10. Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol 2003; 38: 843–53.

[11] 11. Skolnick AH, Alexander KP, Chen AY. Characteristics, management, and outcomes of 5,557 patients age > or = 90 years with acute coronary syndromes: results from the CRUSADE Initiative. J Am Coll Cardiol 2007; 49: 1790–7.

[12] 12. GRACE Investigators. Rationale and design of the GRACE (Global Registry of Acute Coronary Events) project: a multinational registry of patients hospitalized with acute coronary syndromes. Am Heart J 2001; 141: 190–9.

[13] 13. Alexander KP, Chen AY, Roe MT. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA 2005; 294: 3108–16.

[14] 14. Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic complications of anticoagulant and thrombolytic treatment. Chest 2008; 133: 257S–98S.

[15] 15. Hyleck EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689–96.

[16] 16. Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005; 118: 612–7.

[17] 17. Garcia D, Regan S, Crowther M. Warfarin maintenance dosing patterns in clinical practice. Chest 2005; 127: 2049–56.

[18] 18. Klein TE, Altman RB, Eriksson N. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360: 753–764.

[19] 19. Crum RM, Anthony JC, Bassett SS and Folstein MF. Population-based norms for the mini-mental state examination by age and educational level. JAMA. 1993; 18: 2386-2391.

[20] 20. J A Mirallas Martinez. M^aC Real Collado. Indice de Barthel o Medida de independencia functional. Rehabilitación (Madr). 2003; 37: 152-7.

[21] 21. Bellelli G, Bianchetti A, Trabucchi M. Anticoagulation to prevent stroke in atrial fibrillation: comprehensive geriatric evaluation should be routine before treatment is started [letter]. BMJ 2000; 321: 1157.

[22] 22. Palareti G, Poggi M, Guazzaloca G, Savino A, Coccheri S. Assessment of mental ability in elderly anticoagulated patients: its reduction is associated with a less satisfactory quality of treatment. Blood Coagul Fibrinolysis 1997; 8: 411-417.

[23] 23. Bellelli G, Guerini F, Bianchetti A, Trabucchi M. Anticoagulation in disabled patients [letter]. Arch Intern Med 2002; 162: 107-108.

[24] 24. Beyth RJ, Quinn L, Landefeld CS. A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin: a randomized, controlled trial. Ann Intern Med 2000; 133: 687-695.

[25] 25. Tang EO, Lai CS, Lee KK, Wong RS, Cheng G, Chan TY. Relationship between patients’ warfarin knowledge and anticoagulation control. Ann Pharmacother. 2003; 37: 34-39.

Perfil clínico de los pacientes adultos mayores anticoagulados con warfarina del Hospital Nacional de Geriatría y Gerontología

Clinical Profile of Elderly Patients on Anticoagulation with Warfarin

Resúmenes

Perfil clínico de los pacientes adultos mayores anticoagulados con warfarina del Hospital Nacional de Geriatría y Gerontología

(Clinical Profile of Elderly Patients on Anticoagulation Therapy with Warfarin)

Resumen

Abstract

Materiales y métodos

Resultados

Discusión

Referencias

Referencias bibliográficas

Fechas de Publicación

Histórico