早产儿贫血的发生机制与防治进展

贫血是早产儿生后常见的现象,而且出生体质量越低,贫血出现越早,程度越重,持续时间也越长.促红细胞生成素水平低下是早产儿贫血最主要的原因,而医源性失血是早产儿生后2周内早期贫血的重要原因.防治早产儿贫血的措施包括减少医源性失血、合理使用重组人类红细胞生成素、掌握严格的输血指征等.该文主要就早产儿贫血的病因、治疗及预防现状等方面作一综述.     

苯丙酸诺龙对早产儿贫血和体重的影响

早产儿贫血是较常见的现象，所有早产儿生后前几周均发现血红蛋白下降而出现贫血，而且出生体重越低，贫血程度越严重，持续时间也越长，其病因尚不完全清楚。有作者认为促红细胞生成素(E—po)水平低下是早产儿贫血的主要原因。但纠正贫血的方法国内仍以传统输血为主，间以补充VitE、叶酸、铁剂等造血药物。而输血存在某些风险，国内外已有试用基因重组红细胞生成素治疗早产儿贫血的报道，     

早产儿贫血现状及防治研究进展

随着现代医疗技术水平的不断提高,早产儿存活率也在不断提高,但早产儿贫血目前仍是早产儿营养管理上的常见问题之一。防治早产儿贫血的主要方法有不同途径的补充铁剂、红细胞输注及合理使用重组人红细胞生成素等,但上述防治方法各有利弊。文章就早产儿贫血的现状及防治方面进展进行论述。     

造血器官及血液疾病

063742珠海市城区3~6岁儿童常见血液病发生率的调查/崔娓…∥中国儿童保健杂志.-2006,14(4).-392~394063743重组人类红细胞生成素防治早产儿贫血的临床研究/黄晓虹…∥中国儿童保健杂志.-2006,14(3).-286~288将56例早产儿随机分3组,其中大剂量组于生后第8d给促红细胞生成素(r h     

国产重组人类促红细胞生成素防治早产儿贫血的临床效果研究

为评价国产重组人类促红细胞生成素（rhEPO）防治早产儿贫血的效果和安全性，将40例胎龄≤34周的早产儿随机分为治疗组及对照组各20例。治疗组予国产rhEPO750IU／（kg.w），每周分3次皮下注射，用药6周；对照组未用rhEPO；两组早产儿均口服铁剂。结果显示治疗组用药后血清促工细胞生成素水平显著高于对照组（P＜0．01）；治疗组血红蛋白、红细胞压积比、网积红细胞显著高于对照组（P＜0．01）；血清铁蛋白水平在用药后治疗组明显低于对照组（P＜0．01）；治疗组输血率较对照组明显减少（P＜0．01）；治疗组体重增长指标高于对照组9P＜0．05）。研究提示，国产rhEPO能有效防治早产儿贫血，且用药安全，无明显副作用。     

促红细胞生成素治疗早产儿贫血的疗效评定

为了验证人基因重组促红细胞生成素注射剂(EPO)对早产儿贫血的治疗效果,将53例早产儿贫血患儿随机分为EPO治疗组(31例)和对照组(22例),治疗组予以EPO 200IU/kg皮下注射,每周2次,8周后两组间外周血血红蛋白、红细胞、红细胞压积出现显著性差异(P＜0.001),治疗组上述指标均显著高于对照组,且无明显副作用,说明EPO治疗早产儿贫血安全有效.     

早产儿贫血时血清促红细胞生成素的动态变化

目的：探讨促红细胞生成素（ＥＰＯ）与早产儿贫血的关系。方法：采用放射免疫法检测１６例早产儿血清ＥＰＯ、血红蛋白（Ｈｂ）、红细胞压积比（φＲＢＣ）、网织红细胞计数（Ｒｅｔ）、股静脉氧分压（ＰｖＯ２）的动态变化。结果：①早产儿ＥＰＯ水平生后逐渐下降，第３周末最低，以后缓慢上升，但至第５周末仍低于成年男性水平。②当早产儿Ｈｂ下降引起组织缺氧时，ＥＰＯ水平增高，但增高的幅度明显低于成年男性。③ＰｖＯ２＜３７ｋＰａ时，ＥＰＯ浓度均上升。④胎龄越小，ＥＰＯ水平越低。结论：ＥＰＯ水平低下是导致早产儿贫血的主要因素，为应用重组人类促红细胞生成素（ｒｈＥＰＯ）治疗早产儿贫血提供了理论依据。     

促红细胞生成素在早产儿贫血和脑保护方面的研究进展

随着对促红细胞生成素(EPO)相关分子生物学研究的进展,早产儿贫血依赖输血的状况得以改观.EPO是组织氧合状态的一种主要因素,通过结合细胞表面特异性细胞受体而发挥作用,早产儿使用重组EPO可减少需要输血次数和输血总量.EPO的神经保护作用也得以证实.     

促红细胞生成素治疗早产儿贫血的疗效评定

为了验证人基因重组促红细胞生成素注射剂（EPO）对早产儿贫血的治疗效果，将53例早产儿贫血患儿随机分为EPO治疗组（31例）和对照组（22例），治疗组予以EPO 200IU／kg皮下注射，每周2次，8周后两组间外周血血红蛋白、红细胞、红细胞压积出现显著性差异（P＜0．001），治疗组上述指标均显著高于对照组，且无明显副作用，说明EPO治疗早产儿贫血安全有效。     

叶酸与维生素B12在强化促红细胞生成素促进早产儿造血中作用的研究

促红细胞生成素(erythropoietin,EPO)联合铁剂防治早产儿贫血已为大家广泛采用,而作为影响造血的另外两种物质:叶酸,Vitamin B12的作用尚不明确,事实上,早产儿在出生时及出生后的生长需求较足月儿处于缺乏状态,几乎2/3的早产儿在生后1～3个月经历着低叶酸的水平[1].     

Anemia of prematurity

Physiologic anemia is a common and normal finding in newborn infants. In preterm infants, anemia of prematurity is the result of this normal physiologic process compounded by the morbidity of prematurity. Premature infants reach their nadir hematocrit sooner and at a lower level than term. This article reviews the physiology of stem cell differentiation and the structure and function of the red blood cell, as well as examining red blood cell indices. It also addresses the etiology, symptomatology, diagnostic workups and treatment/prevention modalities of anemia of prematurity. Treatment for and prevention of anemia of prematurity remain controversial, and specific criteria are lacking.     

Recombinant human erythropoietin in anemia of prematurity

OBJECTIVE: To evaluate safety and efficacy of recombinant human erythropoietin (r-HuEPO)in reducing the need for red cell transfusions in anemia of prematurity. METHODS: forty -two preterm infants (gestational age <32 weeks) were randomly assigned to a "treatment" group (r-HuEPO 400 units/kg every alternate day * 10 doses) or "no treatment" (control) group. All infants on enteral feeds received oral iron 3 mg/kg/day, graded up to 6 mg/kg/day. RESULTS: Higher reticulocyte counts in week 2 and 3 and higher hemoglobin levels in week 4 were noted after treatment with r-HuEPO. Despite stumulated erythropoiesis, the frequency of transfusions could not be reduced with r-HuEPO therapy.Overall, Phlebotomy losses, frequency and volume of redcell transfusions were significantly more in neonates with birthweight <1000 grams compared with those with birthweight >1000 grams (p<0.05). Associated side effects of r-HuEPO such as neutropenia,sepsis, hypertension or increased risk of late death did not occur. CONCLUSION:r-HuEPO therapy was safe without any side effects.Inability of r-HuEPO therapy to minimize red cell transfusions for anemia of prematurity may be explained by a relatively strict red-cell transfusion policy and the desired degree of treatment effect.     

Erythropoietin to prevent and treat the anemia of prematurity

Human recombinant erythropoietin was first cloned in 1985, and is currently available for clinical use for a variety of anemias. Following successful clinical trials using erythropoietin to treat adults with the anemia of end-stage renal disease, the first clinical trial evaluating the use of erythropoietin in preterm infants to treat anemia was published in 1990. Since that initial report, numerous clinical trials have reported various levels of success in the treatment of this anemia. Most recently, erythropoietin has been used in the first weeks of life in an attempt to prevent the anemia of prematurity. This review describes mechanisms of erythropoiesis in the fetus and neonate, and focuses on recent clinical trials evaluating the use of erythropoietin to prevent and treat anemia in preterm infants.     

Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary?

OBJECTIVE: To examine the number and volume of red blood cell transfusions (RBCTs) in very and extremely low birthweight infants under restrictive red blood cell transfusion guidelines without erythropoietin administration, and to compare the results with those reported in similar infants receiving erythropoietin. METHODS: From April 1996 to June 1999, all RBCTs given to infants with a birth weight of less than 1500 g were prospectively recorded. Data on RBCT combined with erythropoietin treatment and RBCT guidelines were extracted from four prospective randomised trials of erythropoietin for anaemia of prematurity. RESULTS: When the restrictive RBCT guidelines were followed, the number of RBCTs and volume transfused were similar to those reported during erythropoietin administration. CONCLUSIONS: RBCT guidelines may have a similar impact on RBCT in very low birthweight infants to the administration of erythropoietin. The effect of RBCT guidelines on RBCT frequency should be considered when evaluating the efficacy of erythropoietin administration to preterm infants.     

Neonatal anemia

Neonatal anemia and the need for red blood cell (RBC) transfusions are very common in neonatal intensive care units. Neonatal anemia can be due to blood loss, decreased RBC production, or increased destruction of erythrocytes. Physiologic anemia of the newborn and anemia of prematurity are the two most common causes of anemia in neonates. Phlebotomy losses result in much of the anemia seen in extremely low birthweight infants (ELBW). Accepting a lower threshold level for transfusion in ELBW infants can prevent these infants being exposed to multiple donors.     

CERULOPLASMIN LEVELS AND ERYTHROCYTE SUPEROXIDE DISMUTASE ACTIVITY IN SMALL PRETERM INFANTS DURING THE EARLY ANEMIA OF PREMATURITY

Abstract. Hågå, P. (Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Ullevål Hospital, Oslo, Norway). Ceruloplasmin levels and erythrocyte superoxide dismutase activity in small preterm infants during the early anemia of prematurity. Acta Paediatr Scand, 70: 861, 1981.-Ceruloplasmin plasma levels and erythrocyte superoxide dismutase activity were studied in appropriate for gestational age preterm infants (birth weights ≤1500 g) during the first 10 weeks of life. Preterm infants had significantly lower ceruloplasmin concentrations in cord blood than term infants, the mean level in the preterm infants being 0.07 g/I. At 1 week of age ceruloplasmin levels had risen significantly, whereupon a fall occurred at 2 weeks of age. Ceruloplasmin concentrations increased slowly and progressively from 4 weeks of age. The low ceruloplasmin concentration during the early anemia of prematurity seems not to interfere with iron mobilization. The superoxide dismutase activity per gram hemoglobin in cord blood erythrocytes from normal term infants was significantly lower than that of red blood cells from adults. When the activity was expressed per erythrocyte no difference was found. The normochromic macrocytic red blood cells of the neonate most likely explain this discrepancy. The erythrocyte superoxide dismutase activity of the preterm infants did not change from birth until 10 weeks of age, and the levels seemed adequate judged from the levels found in red blood cells from adults and cord blood from term infants. Neither ceruloplasmin nor erythrocyte superoxide dismutase activity seem to play a role in the etiology of the early anemia of prematurity.     

Diffuse neonatal hemangiomatosis in a very low‐birthweight infant treated with erythropoietin

Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the concomitant development of multiple cutaneous infantile hemangiomas (IH) and visceral hemangiomas. Recently, an association between erythropoietin treatment and an increased incidence of infantile hemangioma was noted. A Japanese male infant was born via cesarean section at 27 weeks of gestation. Following the commencement of erythropoietin treatment for anemia of prematurity, he developed multiple cutaneous hemangiomas, high cardiac output heart failure and hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile hepatic hemanigomas, resulting in the final diagnosis of DNH. The discontinuation of erythropoietin treatment and long‐term therapy with propranolol improved the hepatic lesions and cutaneous hemangiomas. The possibility of multiple organ involvement and the exacerbating effects of erythropoietin treatment should be considered in cases in which multiple cutaneous hemangiomas develop in preterm infants receiving erythropoietin treatment.     

Anemia of prematurity: progress and prospects

Recombinant human erythropoietin (r-HuEPO) is of interest to pediatric hematologists and neonatologists because it may prove to be an effective alternative to blood transfusions in preventing and treating anemia in premature infants. The anemia of prematurity is the most promising setting for initial clinical trials. However, it is conceivable that recombinant erythropoietin will be given at birth to low-birth-weight infants in an effort to stimulate endogenous erythropoiesis and thereby prevent some of the erythrocyte transfusions required to replace blood sampled for laboratory tests. Beyond its appeal as a therapeutic alternative to red blood cell transfusions, recombinant human erythropoietin is likely to be the first member of an entirely new class of drugs to be used widely in neonatal medicine. These are drugs produced by cloning normal human genes and expressing them in the laboratory. Because many of the problems of premature birth are caused by developmental immaturity, transiently replacing crucial proteins with exact copies produced by the techniques of recombinant DNA technology is an approach that may have a major impact on morbidity and mortality of neonates. Carefully designed, controlled clinical trials will be essential to determine the role of new agents like r-HuEPO in the treatment of medical problems of premature infants.     

Erythropoietin. Biology and clinical applications.

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.     

Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.