ABSTRACT
Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes.
Subject(s)
Aquaporin 1/biosynthesis , Erythrocytes/metabolism , Gene Expression Regulation , Spherocytosis, Hereditary/blood , Adolescent , Adult , Anemia, Hemolytic, Autoimmune/blood , Anemia, Hemolytic, Autoimmune/genetics , Aquaporin 1/blood , Aquaporin 1/genetics , Biological Transport , Body Water , Cell Line , Child , Child, Preschool , Erythrocyte Membrane/metabolism , Erythrocytes/pathology , Erythropoietin/pharmacology , Hemolysis , Heterozygote , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Middle Aged , Osmolar Concentration , Osmotic Fragility , Spherocytosis, Hereditary/genetics , Spherocytosis, Hereditary/surgery , SplenectomyABSTRACT
Introducción. Con el objetivo de clarificar la controversia sobre la eficacia del hidróxido férrico polimaltosado en relación al sulfato ferroso, se comparó prospectivamente la eficacia y la tolerabilidad deambos.Población, material y métodos. Niños de 6-48 meses,con hemoglobina <11,0 g/dl, volumen corpuscularmedio <72 fl y saturación de transferrina ≤15%o ferritina <16 ng/ml fueron estratificados por gruposetarios y aleatorizados para recibir hidróxidoférrico polimaltosado o sulfato ferroso (5 mg/kg/día)durante 90 días. Se analizaron hemoglobina, hematócrito,volumen corpuscular medio, ferremia, saturacióny ferritina. La tolerabilidad se evaluó comobuena, regular o mala, según el porcentaje de dosisque efectivamente recibía el niño.Resultados. Se incluyeron 59 pacientes (23 con hidróxidoférrico polimaltosado, 36 con sulfato ferroso).Hemoglobina y hematócrito mostraron valores significativamente más elevados en el grupo sulfatoferroso que en el hidróxido férrico polimaltosado desde el día 30 hasta el final (p <0,05). Ferremia,saturación y ferritina al día 90 fueron significativamente mayores en el grupo sulfato ferroso (p <0,05).La diferencia inicial-final fue significativamente mayor en el grupo sulfato ferroso para todas lasvariables. Un mayor porcentaje de pacientes delgrupo sulfato ferroso alcanzó valores normales parahemoglobina, hematócrito, volumen corpuscularmedio, ferremia y saturación (p <0,05). Sólo un paciente del grupo sulfato ferroso (por mala tolerancia)y uno del grupo hidróxido férrico polimaltosado(por caída de hemoglobina >1 g/dl) debieronsuspender tratamiento.Conclusiones. El sulfato ferroso es de elección pues produce incrementos más precoces y de mayor intensidad para todos los parámetros, permite la normalización de valores en mayor cantidad depacientes y presenta similar tolerabilidad y grado de adhesión al tratamiento que el hidróxido férricopolimaltosado.(AU)
Introduction. The usefulness of iron polymaltose (IP) for the treatment of iron deficiency anemia is still controversial. The aim of this prospective, randomized study was to compare efficacy and tolerability of IP and ferrous sulfate (FS). Patients, materials y methods. Children aged 6-48 months, with hemoglobin <11.0 g/dl, mean corpuscular volume <72 fl and transferrin saturation ≤15% or ferritin <16 ng/ml were stratified in age groups and randomized to receive IP or FS (5 mg/kg per day) throughout 90 days. Hemoglobin, hematocrit, mean corpuscular volume, serum iron, transferrin saturation, and ferritin were determined. Tolerability to oral administration was classified as good,intermediate or poor, according to the percentage of the total daily iron dose received. Results. Fifty-nine patients (23 IP, 36 FS) were included. Hemoglobin and hematocrit showed significantly higher values in group FS than in group IP from day 30 to the end of the study (p <0.05). Serum iron, saturation and ferritin at day 90 were significantly higher in group FS (p <0.05). The difference between initial and final values was significantly higher in group FS for every determination. Normal values for hemoglobin, hematocrit, mean corpuscular volume, serum iron and saturation were achieved by significantly more patients in group FS (p <0.05). Only one patient in group FS (due to poor tolerance) and another in group IP (due to hemoglobin fall >1 g/dl) had to discontinue treatment. Conclusions. The first choice for treatment is FS, since it is more effective, with similar safety, tolerability and compliance profiles than IP.(AU)
Subject(s)
Infant , Child , Hydroxides , Ferrous Sulfate , Anemia, Iron-Deficiency , Iron Deficiencies , Prospective Studies , Random AllocationABSTRACT
Introducción. Con el objetivo de clarificar la controversia sobre la eficacia del hidróxido férrico polimaltosado en relación al sulfato ferroso, se comparó prospectivamente la eficacia y la tolerabilidad deambos.Población, material y métodos. Niños de 6-48 meses,con hemoglobina <11,0 g/dl, volumen corpuscularmedio <72 fl y saturación de transferrina ≤15%o ferritina <16 ng/ml fueron estratificados por gruposetarios y aleatorizados para recibir hidróxidoférrico polimaltosado o sulfato ferroso (5 mg/kg/día)durante 90 días. Se analizaron hemoglobina, hematócrito,volumen corpuscular medio, ferremia, saturacióny ferritina. La tolerabilidad se evaluó comobuena, regular o mala, según el porcentaje de dosisque efectivamente recibía el niño.Resultados. Se incluyeron 59 pacientes (23 con hidróxidoférrico polimaltosado, 36 con sulfato ferroso).Hemoglobina y hematócrito mostraron valores significativamente más elevados en el grupo sulfatoferroso que en el hidróxido férrico polimaltosado desde el día 30 hasta el final (p <0,05). Ferremia,saturación y ferritina al día 90 fueron significativamente mayores en el grupo sulfato ferroso (p <0,05).La diferencia inicial-final fue significativamente mayor en el grupo sulfato ferroso para todas lasvariables. Un mayor porcentaje de pacientes delgrupo sulfato ferroso alcanzó valores normales parahemoglobina, hematócrito, volumen corpuscularmedio, ferremia y saturación (p <0,05). Sólo un paciente del grupo sulfato ferroso (por mala tolerancia)y uno del grupo hidróxido férrico polimaltosado(por caída de hemoglobina >1 g/dl) debieronsuspender tratamiento.Conclusiones. El sulfato ferroso es de elección pues produce incrementos más precoces y de mayor intensidad para todos los parámetros, permite la normalización de valores en mayor cantidad depacientes y presenta similar tolerabilidad y grado de adhesión al tratamiento que el hidróxido férricopolimaltosado.
Introduction. The usefulness of iron polymaltose (IP) for the treatment of iron deficiency anemia is still controversial. The aim of this prospective, randomized study was to compare efficacy and tolerability of IP and ferrous sulfate (FS). Patients, materials y methods. Children aged 6-48 months, with hemoglobin <11.0 g/dl, mean corpuscular volume <72 fl and transferrin saturation ≤15% or ferritin <16 ng/ml were stratified in age groups and randomized to receive IP or FS (5 mg/kg per day) throughout 90 days. Hemoglobin, hematocrit, mean corpuscular volume, serum iron, transferrin saturation, and ferritin were determined. Tolerability to oral administration was classified as good,intermediate or poor, according to the percentage of the total daily iron dose received. Results. Fifty-nine patients (23 IP, 36 FS) were included. Hemoglobin and hematocrit showed significantly higher values in group FS than in group IP from day 30 to the end of the study (p <0.05). Serum iron, saturation and ferritin at day 90 were significantly higher in group FS (p <0.05). The difference between initial and final values was significantly higher in group FS for every determination. Normal values for hemoglobin, hematocrit, mean corpuscular volume, serum iron and saturation were achieved by significantly more patients in group FS (p <0.05). Only one patient in group FS (due to poor tolerance) and another in group IP (due to hemoglobin fall >1 g/dl) had to discontinue treatment. Conclusions. The first choice for treatment is FS, since it is more effective, with similar safety, tolerability and compliance profiles than IP.