Guía para Uso de Componentes Sanguíneos

Niveles de Hemoglobina en Pacientes con Neoplasias Malignas

I Instituto de Evaluación Tecnológica en Salud

7.7 Intervención para Mejorar los Niveles de Hemoglobina en Pacientes con Neoplasias Malignas(Pregunta de antecedentes)

En pacientes con malignidades (tumores sólidos) sometidos a radioterapia, ¿las intervenciones (transfusión o AEE) dirigidas a aumentar la concentración de Hb durante la radioterapia afectan los resultados del paciente (ej. la tasa de respuesta, la recurrencia del tumor o la supervivencia libre de tumor)?

Evidencia

7.7.1 Hipoxia tumoral: fisiopatología y efectos

Se observan áreas hipóxicas distribuidas heterogéneamente (pO2 <2,5 mm Hg) en hasta 60% de tumores sólidos localmente avanzados, como cáncer de mama, uterino, cervical, de cabeza, cuello y recto, sarcomas de tejidos blandos y melanomas malignos (143). Una alta incidencia de las áreas hipóxicas se ha correlacionado con el comportamiento agresivo del tumor y una propensión a la metástasis.

La hipoxia afecta las vías de señalización que intervienen en la angiogénesis, el transporte de glucosa, la regulación del pH y la eritropoyesis (144). Por lo tanto, los tumores se vuelven hipóxicos debido al desarrollo de una vasculatura anormal. La familia de factores inducibles por hipoxia (HIF) es importante en la respuesta celular a la homeostasis del oxígeno; la sobre-expresión del HIF-1 en cáncer se correlaciona con un mal diagnóstico y un aumento de la agresión tumoral. La hipoxia sostenida del tumor altera la respuesta a la radiación y a muchos agentes quimioterapéuticos en las líneas celulares, pero este efecto también depende del pH micro-ambiental y de la depleción de la glucosa.

La anemia es común en pacientes con tumores sólidos, y está relacionada con la malignidad y el tratamiento del tumor. Se ha observado una asociación entre los bajos niveles de hemoglobina y el mal resultado tanto de la radioterapia como de la quimioterapia (146-147) en varios tumores sólidos. La reducción de la capacidad de transporte de oxígeno en la sangre en la anemia, puede ser un factor importante en la hipoxia tisular, porque la vasculatura anormal del tumor es menos capaz de compensar la anemia mediante el aumento de la perfusión tisular.

Hipoxia tumoral y resistencia a la radioterapia

Los fotones de alta energía utilizados en la radioterapia inducen el daño del ácido desoxirribonucleico (ADN). Los fotones pueden causar directamente electrones para ionizar los átomos de hélice del ADN, o pueden producir especies altamente reactivas de radicales libres, que luego interactúan con el ADN y lo dañan. El daño irreparable del ADN inhibe la proliferación celular y conduce a la muerte celular. La presencia de oxígeno contribuye al proceso indirecto al prolongar la vida útil de los radicales libres. El oxígeno también disminuye la capacidad de las células para reparar el daño del ADN, de modo que las células bien oxigenadas son más radiosensibles que las células hipóxicas.

La hipoxia también puede contribuir a la resistencia a la radiación tumoral. Esto puede ser causado por la alteración de la cinética de proliferación celular, la reducción de la apoptosis y la diferenciación, y el crecimiento celular reducido asociado con un proceso de síntesis de proteínas más lento. La hipoxia también puede aumentar la progresión maligna y la agresividad a través de la selección clonal y cambios en el genoma, con un efecto adverso en los resultados del paciente.

Impacto de la corrección de la anemia en el resultado de la radioterapia

La anemia (con umbrales de Hb de 90-145 g/L (9-14.5 g/dL)) se ha asociado con una respuesta reducida a la terapia y una supervivencia acortada en el cáncer cervical, vesical, bronquial y de cabeza y cuello (148).

Agentes estimulantes de la eritropoyesis

Los AEE reducen la terapia de la anemia y la necesidad de transfusión (82-149). Sin embargo, la supervivencia libre de progresión local-regional fue significativamente peor en el brazo de tratamiento en un gran ensayo multicéntrico controlado con placebo de fase III de terapia con AEE en pacientes sometidos a radioterapia para cáncer de cabeza y cuello (150).

Una revisión de Cochrane (151) examinó el uso de AEE con radioterapia o quimioterapia en pacientes con cáncer de cabeza y cuello, y demostró una menor supervivencia en pacientes que recibieron AEE, aunque la Hb diana fue más alta de lo que actualmente se consideró apropiado en cuatro de los cinco ensayos incluidos.

El ensayo 0191 del Gynecologic Oncology Group (GOG) evaluó el efecto del uso de AEE para mantener la Hb a 100 g/L (10 g/dL) en comparación con el tratamiento con AEE o transfusión a una Hb de 120 -130 g/L (12 – 13 g/dL) en mujeres con cáncer cervical localmente avanzado (152). El estudio se acabó prematuramente debido al aumento de los eventos tromboembólicos en el último brazo. La supervivencia libre de progresión a tres años y la supervivencia global fueron inferiores en el grupo de tratamiento con AEE.

Los desenlaces adversos pueden resultar de un exceso de eventos tromboembólicos entre pacientes tratados con un umbral de Hb alto. Los AEE también pueden promover la progresión del tumor, porque los receptores de eritropoyetina pueden expresarse en la superficie de algunas líneas celulares tumorales.

La transfusión de glóbulos rojos

La opinión de que la transfusión de glóbulos rojos para mantener una Hb de 125 g/L (12.5 g/dL) en pacientes sometidos a radioterapia para tumores sólidos, se asocia con una tasa de recaída local reducida se basa en una publicación de 1978 (153). Sin embargo, el análisis posterior del estudio basado en la intención de tratar, demostraron que no había ninguna diferencia en la mortalidad relacionada con la enfermedad. Un estudio reciente que evaluó la importancia pronostica de la anemia y su modificación por transfusión en pacientes con cáncer de cabeza y cuello tratados con radioterapia no mostró ningún beneficio (154). La transfusión puede mejorar el suministro de oxígeno en pacientes profundamente anémicos, pero no supera necesariamente otros factores que conducen a hipoxia tumoral.

Se ha propuesto que el aumento de la morbilidad y la mortalidad en los pacientes transfundidos se deben a la inmunosupresión. (155-157) La revisión de Varlotto y Stevenson (158) concluyó que la corrección de la anemia por transfusiones de sangre ha tenido un efecto adverso sobre la supervivencia del paciente. Los autores postularon que esto se debía a la modulación de vías inflamatorias o inmunosupresoras.

La relación entre la anemia, la hipoxia tumoral y los efectos del tratamiento para corregir la anemia en pacientes con tumores sólidos es mucho más compleja de lo inicialmente percibido. La hipoxia está probablemente muy relacionada de forma predominante con la vasculatura tumoral anormal, y no se ha demostrado que la corrección de la anemia mejore el resultado de la radioterapia. El uso de AEE, particularmente con umbrales de Hb más altos, se ha asociado con un impacto adverso en la supervivencia en pacientes con malignidad.

7.7.2 Evaluación de los pacientes después de la transfusión de glóbulos rojos. (Pregunta de antecedentes)

¿Cuándo se debe volver a evaluar a un paciente después de una transfusión para determinar la respuesta, para guiar la necesidad de transfusiones adicionales y evitar la sobretransfusión?

Evidencia

Cuando se prescribe una transfusión de glóbulos rojos, decidir cuántas unidades transfundir es tan importante como la propia decisión transfusional, ya que cada transfusión de la unidad conlleva riesgos adicionales.

Existe un creciente número de publicaciones sobre los umbrales de Hb o criterios apropiados para la transfusión de glóbulos rojos, tanto en pacientes con patología general como en varios subgrupos clínicos. Sin embargo, estos estudios generalmente no abordan la cuestión de la sobre-transfusión y sus riesgos asociados, que son de significativa importancia práctica (159-160).

Cuando se considera la decisión de transfundir y la dosis, es mejor realizar una evaluación clínica cuidadosa de los pacientes. Debe llevarse a cabo la transfusión de una sola unidad, con una evaluación clínica posterior tras la transfusión. No se requieren más transfusiones si se alivian los signos y síntomas. La experiencia clínica sugiere que muchos pacientes pueden tardar 24 horas o más en reportar una mejoría en los síntomas.

En algunas situaciones, puede ser apropiado prescribir más de una unidad a la vez

Por ejemplo, cuando hay pérdida significativa o anticipada de sangre, anemia severa o el paciente tiene necesidades crónicas de transfusión (ej. falla de la médula ósea). El número de unidades prescritas, sin embargo, todavía debe ser cuidadosamente considerado sobre la base de los factores individuales del paciente.

Hay poca información en la literatura acerca de cuándo se debe probar el nivel de Hb después de una transfusión de glóbulos rojos. Cuando se indica, la transfusión de una sola unidad de GR seguida de reevaluación clínica es apropiada. Esta evaluación guiará la decisión sobre si volver a determinar el nivel de Hb. Un estudio informó una alta correlación entre los niveles de Hb tomados a los 15 minutos, 1 hora y 2 horas después de la transfusión (161).

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Instituto de Evaluación Tecnológica en Salud

IETS Colombia - Instituto de Evaluación Tecnológica en Salud. Instituto de Evaluación Tecnológica en Salud. Fue creado en el 2011 según lo estipulado en la Ley 1438, como una corporación sin ánimo de lucro, con participación de entidades públicas y privadas. De acuerdo con el Departamento Administrativo de la Función Pública, nuestro Instituto es una entidad descentralizada del sector de la salud. Es la Agencia Nacional de Evaluación de Tecnología Sanitaria de Colombia, que genera evidencia con rigor científico para soportar la toma de decisiones, promueve el desarrollo de mejores políticas públicas y prácticas asistenciales en salud con el fin de contribuir al mejoramiento de la salud de los colombianos, y a la sostenibilidad del sistema con legitimidad, innovación, calidad, equidad y eficiencia.

Anterior Siguiente

7.7 Intervención para Mejorar los Niveles de Hemoglobina en Pacientes con Neoplasias Malignas(Pregunta de antecedentes)

Evidencia

7.7.1 Hipoxia tumoral: fisiopatología y efectos

Hipoxia tumoral y resistencia a la radioterapia

Impacto de la corrección de la anemia en el resultado de la radioterapia

Agentes estimulantes de la eritropoyesis

La transfusión de glóbulos rojos

7.7.2 Evaluación de los pacientes después de la transfusión de glóbulos rojos. (Pregunta de antecedentes)

Evidencia

En algunas situaciones, puede ser apropiado prescribir más de una unidad a la vez

Referencias

1. National Health and Medical Research Council (NHMRC) and Australasian Society of Blood Transfusion (ASBT) (2001). Clinical practice guidelines on the use of blood components, NHMRC, Canberra, Australia. http://www.nhmrc.gov.au/_files_nhmrc/file/publications/synopses/cp78.pdf

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