RESUMO
In seven patients with bronchopulmonary dysplasia and anemia, we evaluated the mechanisms causing the anemia. All had a normocytic, normochromic, hyporegenerative anemia (mean hematocrit 26%; range 21% to 30%). The low hematocrit values seemed physiologically significant because mean (+/- SD), heart rates fell after transfusion (162 +/- 7 to 149 +/- 9 beats/min; p less than 0.005), as did blood lactate concentrations (1.2 +/- 0.3 mumol/gm blood before vs 0.5 +/- 0.3 after transfusion; p less than 0.05). Anemia could not be explained by blood withdrawal or deficiency of vitamin E, folate, or iron. No dyserthropoietic or megaloblastic changes were observed. No erythroid regenerative response was seen in the marrow; however, when recombinant erythropoietic growth factors were added to marrow cells in tissue culture, erythroid cell growth in vitro was normal. In contrast to patients with the "anemia of chronic disorders," these patients had a normal or increased number of marrow sideroblasts and increased serum transferrin saturation. Serum concentrations of erythropoietin were low for patients with anemia (range 11.4 to 47.1 mU/ml); yet the in vitro sensitivity of bone marrow erythroid progenitors (colony-forming units--erythroid) to recombinant erythropoietin was increased (p less than 0.001). We conclude that the anemia in these patients was the result of deficient production of erythropoietin, and we speculate that administration of recombinant erythropoietin would correct the anemia.
Assuntos
Anemia/etiologia , Displasia Broncopulmonar/complicações , Anemia/patologia , Anemia/fisiopatologia , Bilirrubina/sangue , Exame de Medula Óssea , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Células Cultivadas , Células Precursoras Eritroides/efeitos dos fármacos , Eritropoetina/sangue , Eritropoetina/farmacologia , Feminino , Ferritinas/sangue , Frequência Cardíaca , Hematócrito , Humanos , Lactente , Recém-Nascido , Lactatos/sangue , Ácido Láctico , Masculino , Proteínas Recombinantes , Células-Tronco/patologia , Transferrina/análise , Vitamina E/sangueRESUMO
We used cells from marrow aspirations that had been performed on 10 infants with the "anemia of prematurity" and tested the responsiveness of their erythroid colony-forming units (CFU-E) to recombinant human erythropoietin. For comparison, we also tested marrow-derived CFU-E from five healthy adults, and circulating CFU-E from cord blood of five healthy neonates. CFU-E from the anemic infants had a 50% maximal response at 0.073 +/- 0.024 U erythropoietin per milliliter (mean +/- SD). They were therefore at least as responsive as were CFU-E from adults, which displayed a 50% maximal response at 0.118 +/- 0.076 U/ml, and as were circulating CFU-E of cord blood origin, which had a 50% maximal response at 0.109 +/- 0.047 U/ml. Because CFU-E from infants with the "anemia of prematurity" appeared highly sensitive to erythropoietin in vitro, we propose that its administration to these patients would likely result in a significant increase in erythrocyte production in vivo.
Assuntos
Anemia Neonatal/fisiopatologia , Eritropoetina/farmacologia , Células-Tronco/fisiologia , Medula Óssea/fisiologia , Sangue Fetal/fisiologia , Humanos , Técnicas In Vitro , Recém-Nascido , Doenças do Prematuro/fisiopatologiaRESUMO
In groups of adults, and term and preterm neonates, we determined: the blood concentration, the proliferative rate, and the variety of progeny of committed granulocyte-macrophage progenitor cells (CFU-GM). In five of eight term neonates and in all premature infants, a potentially significant limitation of neutrophil production was detected. Unlike the slowly proliferating CFU-GM present in the blood of healthy adult subjects (7% thymidine suicide, range 0% to 32%), the circulating CFU-GM in the premature subjects were proliferating at a near maximal rate (55%, range 40% to 75%, P less than 0.001). Because CFU-GM proliferation is nearly maximal in the baseline, noninfected state, neonates may have restricted ability to increase neutrophil production from CFU-GM during times of increased neutrophil need, such as during bacterial infection. Such inability may predispose neonates to exhaustion of the neutrophil supply during bacterial infection.
Assuntos
Granulócitos/análise , Células-Tronco Hematopoéticas/análise , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Macrófagos/análise , Adulto , Animais , Ensaio de Unidades Formadoras de Colônias , Sangue Fetal/análise , Humanos , RatosRESUMO
The leukocyte left shift is commonly used as an adjunct to the early diagnosis of bacterial infection. Many different methods have been employed for its quantification, such as the absolute band count, band/seg ratio, band/total neutrophil ratio, and immature/total neutrophil ratio. We examined blood and bone marrow samples in groups of noninfected and infected neonatal dogs and human beings in order to determine which method most clearly reflects an increased call upon marrow neutrophil reserves and which correlates best with the presence and severity of infection. We found that the neutrophil ratios were more frequently abnormal during neonatal sepsis than was the the absolute band count. All subjects, canine and human, in whom the immature/total neutrophil ratio exceeded 0.800 were found to have depletion of the marrow neutrophil reserves, and those with the most profound depletion died. This study supports the concept that an elevated immature/total neutrophil ratio can aid in the diagnosis of bacterial infection in the newborn infant and suggests that the degree of elevation may serve as a method for detecting subjects at high risk for depletion of the marrow neutrophil reserves and death from sepsis.