ABSTRACT
RESUMEN: Introducción: Los pacientes con eritrocitosis patológicas en la altura, Eritrocitosis Secundaria o Eritrocitosis Patológica de Altura, ocasionalmente suelen presentar niveles de eritropoyetina (EPO) con variaciones notables respecto de los parámetros normales, reflejando ya sea concentraciones muy bajas o muy altas de EPO. Objetivo: Analizar la prevalencia de las eritrocitosis con EPO disminuida y de las eritrocitosis con EPO incrementada, así como, las características laboratoriales y clínicas inmiscuidas entre ellas. Material y Métodos: Se realizó un estudio descriptivo transversal de tipo retrospectivo. Se analizó historias clínicas de 44 pacientes eritrocíticos; de estos, 22 pacientes (5 mujeres, 17 varones) con registros de EPO sérica disminuida (100 mUI/ml) que constituyeron el Grupo 2. Todos ellos residentes a una altura >3650 m s. n. m. Se recolectó datos demográficos, clínicos y laboratoriales; asimismo, datos referentes a los tratamientos administrados, seguimiento y respectivas respuestas en ambos grupos. Resultados: La frecuencia de las eritrocitosis patológicas con EPO disminuida representó 5 % y de aquellas con EPO elevada 5 %.: Se debe considerar estudios específicos en pacientes eritrocíticos con EPO baja para descartar Policitemia Vera, asimismo, los pacientes con EPO incrementada implican mayor complejidad en el manejo médico.
ABSTRACT: Introduction: Patients with pathological erythrocytosis at high altitude, Secondary Erythrocytosis or High Altitude Pathological Erythrocytosis, occasionally present notable variations of erythropoietin (EPO) levels regarding normal parameters, reflecting either very low or very high EPO concentrations. Objective: To analyze the prevalence of erythrocytosis with decreased EPO and erythrocytosis with increased EPO, as well as the laboratory and clinical characteristics involved between them. Material and methods: A retrospective cross-sectional descriptive study was conducted. Clinical records of 44 patients with erythrocytosis were analyzed; of these, 22 (5 women, 17 men) with records of decreased serum EPO (100 mIU/ml) ml) specified as Group 2. All of them were high altitude dwellers (>3650 m a. s. l). Demographic, clinical and laboratory data were collected, including data about administered treatments, follow-up and responses in both groups. Results: Frequency of pathological erythrocytosis with decreased EPO was 5% and with elevated EPO 5%. There were no representative differences between both groups concerning the CBC variables. Patients with increased EPO showed more complications of erythrocytosis (27%) compared to those with decreased EPO (0%). Two types of treatment regimen were evidenced in each group: a) ATV+ASA, and b) ATV+ASA+HU. Erythrocytosis patients with decreased EPO receiving ATV+ASA had higher favorable responses 90% versus those with elevated EPO (80%). The ATV+ASA+HU regimen reflected better applicability in the increased EPO group. Conclusion: Specific studies should be considered in erythrocytosis patients with decreased EPO to rule out Polycythemia Vera, similarly, patients with increased EPO imply more complexity at medical management.
Subject(s)
Erythropoietin , LaboratoriesABSTRACT
Introducción. Los pobladores de grandes alturas se adaptaron de modo diferentes, siguiendo rutas distintas con el mismo objetivo de suministro de oxígeno y la supervivencia. En el presente trabajo se caracteriza la Eritrocitosis Patológica de Altura y se demuestra la eficacia de la atorvastatina en el tratamiento. Material y métodos. Se estudiaron: Sujetos varones como Controles Normales (CN), y pacientes con Eritrocitosis Patológica de Altura (EPA), Eritrocitosis Secundaria (ES) y Policitemia Vera (PV). Se realizaron estudios de laboratorio y de biología molecular. Se realizó estudio clínico de fase 2 con atorvastatina. Resultados. La EPA presenta: eritropoyetina normal, apoptosis retardada de progenitores eritroides, crecimiento autónomo de BFU-E e hipersensibilidad a la eritropoyetina. La atorvastatina como tratamiento en pacientes con EPA disminuye la concentración de hemoglobina y remite la sintomatología de la hiperviscosidad sanguínea. Conclusiones. La EPA tiene características propias que la distinguen de otras eritrocitosis patológicas y la atorvastatina se constituye en tratamiento eficaz.
Introduction. The residents of high altitude get use to it in different ways, following the same purpose in order to supply oxygen and survival. In the present paper, we characterize the High Altitude Pathological Erythrocytosis disease and demonstrate the effectiveness of atorvastatin in its treatment. Material and methods. We studied male subjects as normal controls (CN), and patients with High Altitude Pathological Erythrocytosis (EPA), Secondary Erythrocytosis (ES) and Polycythemia Vera (PV). Laboratory and molecular biology studies were conducted. We developed in the study of 2nd phase with atorvastatin. Results. The EPA presents: normal erythropoietin, delayed erythroid progenitors apoptosis, autonomous growth of BFU-E and hypersensitivity to erythropoietin. The atorvastatin in patient with EPA, decreased hemoglobin concentration and eliminates the symptomatology of blood hyperviscosity Conclusions. The EPA has characteristics that distinguish it from other pathologic erythrocytosis and atorvastatin becomes an effective treatment.
Subject(s)
PolycythemiaABSTRACT
Introducción La Eritrocitosis Patológica de Altura es la manifestación hematológica de la Enfermedad Crónica de Altura, por adaptación inadecuada a grandes alturas de genes reguladores de la eritropoyesis. Las estatinas son inhibidores de la vía del mevalonato involucrado en la regulación de la eritropoyesis. El presente trabajo describe los mecanismos moleculares de la inhibición de la eritropoyesis en pacientes con eritrocitosis patológicas. Material y métodos Se estudiaron 35 pacientes con eritrocitosis patológicas con radicatorias en las ciudades de La Paz y El Alto (3600 y 4000 msnm respectivamente). Se realizaron Cultivo de células progenitoras hematopoyéticas y Western Blot. Resultados Statins induce apoptosis of erythroid progenitors in the cell culture medium. Without the supplement of simvastatin the apoptosis was 12.3% and With simvastatin the apoptosis was 38.4% (p = 0.001). Furthermore statins inhibit the proliferation and differentiation of erythroid progenitors. Conclusiones Los mecanismos moleculares involucrados en la inhibición de la eritropoyesis son: a) Bloqueo de la isoprenilación de Rho y Ras, b) Inhibición de la fosforilación de Jak-2 y Stat-5, c) inhibición de la glicosilación del EpoR, d) Disminución de colesterol en microdominios de la membrana celular (raft lipid), e) Inducción de apoptosis a través de BCLxL y caspasa 9.
Introduction The High altitude Pathological Erythrocytosis is the chronic mountain sickness hematologic manifestation by inadequate adaptation to high altitudes of genes regulating erythropoiesis. Statins are inhibitors of the mevalonate pathway involved in the regulation of erythropoiesis. This paper describes the molecular mechanisms of erythropoiesis inhibitionin patients with pathological erythrocytosis. Material and methods We studied 35 patients with pathological erythrocytosis from La Paz and El Alto city (3600 and 4000 masl respectively). Were performed hematopoietic progenitor cell culture and Western blotting. Results Statins induce apoptosis in liquid culture medium. without simvastatin erythroid progenitors from apoptosis presentarón and 12.3% in the group supplemented with simvastatin 38.4% apoptosis (p = 0.001), statins also inhibit the proliferation and differentiation of erythroid progenitors, and inhibit transcription of STAT-5. Conclusions The molecular mechanisms involved in the erythropoiesis inhibition are: a) Inhibition of Ras and Rho isoprenylation, b) Inhibition of Jak-2 and Stat-5 phosphorylation, c) inhibition of EpoR glycosylation, d) Statins reduce lipid rafts cholesterol and reduce JAK2 localization to lipid rafts, e) Induction of apoptosis through caspase 9 and BclxL.