Late Anemia Research Articles

Rhesus disease: postnatal management and outcome.

The incidence of rhesus haemolytic disease has been markedly reduced. Affected infants who have had intrauterine transfusions suffer a late hyporegenerative anaemia. Postnatal haemolysis and hence treatment for hyperbilirubinaemia is less commonly needed. Optimal phototherapy reduces the need for postnatal exchange transfusions, but data on the efficacy of inhibitors of bilirubin production such as haem oxygenase inhibitors or immunoglobulin are less secure. Even hydropic infants have less than 20% mortality and bilirubin encephalopathy is uncommon. There is, however, very limited information on the long-term outcome of infants with rhesus haemolytic disease. Multicentre collaboration is required to test strategies to improve the management of affected individuals further and to provide meaningful data on their prognosis.

Severe late anemia of hemolytic disease of the newborn

Late anemia is a well-recognized complication of Rhesus hemolytic disease of the newborn (HDN). The incidence of Rhesus HDN is declining, with a tendency for more severely affected pregnancies to be managed in specialist centres. Consequently, many paediatric departments may see relatively few affected infants with comparatively mild disease, and the risk of late anemia in such cases may not always be appreciated. Two cases of infants born with evidence of Rhesus isoimmunization noted at birth and encountering no immediate problems other than mild hyperbilirubinemia are described. After an uneventful early neonatal course, both infants were discharged without follow-up and presented in the second to third weeks of life with severe, life-threatening anemia, leading to neurological sequelae in one case. The importance of close surveillance, including hemoglobin measurements, in all infants with Rhesus hemolytic disease, irrespective of initial severity, is reiterated.

Late hyporegenerative anemia in neonates with rhesus hemolytic disease.

This study was conducted to determine the risk factors of the late hyporegenerative anemia in Rh-isoimmunized infants. Data on 36 infants with rhesus hemolytic disease were analyzed. The mean gestational age and birth weight were 36 +/- 1.3 weeks and 2837 +/- 403 grams respectively. Twenty-seven infants (75%) received between 2 and 8 intravascular intrauterine blood transfusions. Fourteen infants (39%) required simple packed red blood cell transfusions and 11 infants (31%) required exchange blood transfusion in the immediate postnatal period. Thirty infants (83%) developed late anemia and required blood transfusions at a mean postnatal age of 43.3 +/- 15.7 days. Sixty-four percent of infants who had exchange blood transfusions did not develop late anemia, while 92% of infants who did not require exchange blood transfusion developed late anemia, and the difference was statistically significant (P = 0.035). Serum erythropoietin levels were determined in 8 infants immediately before simple transfusion for late anemia. The media serum erythropoietin level was 21.2 mU/ml, ranging between less than 10 to 114.2 mU/ml. We conclude that late hyporegenerative anemia is common among Rh isoimmunized infants, regardless of the intravascular intrauterine transfusion. Exchange blood transfusion was associated with less occurrence of late anemia.

Erythropoietin Administration in Term Infants with Hemolytic Anemia. 792

Administration of recombinant erythropoietin (EPO) has been shown to decrease or eliminate the need for erythrocyte transfusion (Tx) in preterm infants and to decrease the need for Tx in late anemia due to Rh or ABO hemolytic disease. The objective of this study was to determine if EPO administration to infants with hemolytic anemia before one month of age will prevent severe anemia and avoid the need for Tx. A planned randomized, controlled study could not be done due to parents' preference for EPO therapy once relative risks of EPO vs transfusion had been explained. Eighteen term infants were treated with EPO between 8/96 and 11/97. The etiology of the hemolytic anemia was as follows: 10 ABO incompatibility (7/10 with positive direct Coombs), 1 hemolytic elliptocytosis, 1 G6PD deficiency, 2 alpha thal. trait, 4 unknown (1 had Hb SS). At the start of EPO therapy, ages were 1.5-3.5 wks (med 2 wks), Hb levels 9-13.5 gm/dL (med 10.1; all but 1 had Hb < 11.4), reticulocytes 0.6-2.6% (med 1.5%). Serum EPO levels in 10 of these infants ranged from 2.5-20.3 mU/mL (med 9.6 mU/mL). All infants received EPO 200 u/kg SC TIW for a duration of 2-5.5 wks (med 3 wks) with oral iron 3 mg/kg day during EPO therapy and for an additional 6 wks. The reticulocyte counts increased 2-10 fold from pre-EPO values in 1-2 wks. Hb levels remained stable or increased during EPO therapy except in 1 infant with OB hemolytic disease who developed a UTI and was transfused for worsening anemia. In most infants the Hb level remained stable or declined slightly (< 1 gm/dL) after EPO was discontinued, but EPO administration was resumed in 1 infant when the Hb level dropped from 11.4 to 10.1 gms/dL during the first week off therapy. No adverse effects were observed from EPO administration. We conclude that serum EPO levels are not increased in term infants with hemolytic anemia. EPO administration results in brisk reticulocyte response with stable or increasing Hb levels and, thus, is likely to prevent or reduce the need for Tx.

ANTIBODY-MEDIATED PERINATAL CYTOPENIAS. 39

Anemia, thrombocytopenia and neutropenia in perinatal period may result from placentally transferred maternal IgG allo or autoantibodies against RBC, Plt and PMN antigens (Ags). Alloantibodies (alloAbs) against RBC Ags most commonly cause of severe fetoneonatal anemia are anti-D and other alloAbs of the Rh system (anti-c, anti-c plus anti-E) as well as anti-Kell. Although maternal anti-D immunoprophylaxis has dramatically reduced the prevalence of feto-neonatal Rh hemolytic disease, during the last decade in our Neonatal Unit 60 affected infants have been observed. More than 70% of them showed early plus late or late severe anemia which had often required prenatal and/or postnatal RBC transfusions (Ts).

NEONATAL ANEMIA: PATHOPHYSIOLOGY AND TREATMENT

All neonates experience a decline in circulating red blood cell (RBC) mass due to diminished erythropoietin (EPO) levels. This effect is more pronounced in small, premature infants and can lead to severe anemia and need for RBC transfusions--particularly, if repeated phlebotomy is required to monitor acutely-ill neonates. Although optimal RBC transfusion therapy has been a long-term challenge for neonatologists, the emergence of recombinant EPO as promising therapy for neonatal anemia is the major issue for 1994. Accordingly, this report for the 12th International Convocation on Immunology (Transfusion Immunology and Medicine) will focus on this aspect of neonatal transfusion medicine. Although several controlled trials to evaluate EPO as therapy have been completed, definitive answers to all questions regarding efficacy and possible toxicity have not been provided. However, therapy with EPO plus iron and adequate nutrition is likely to be proven effective for the relatively late anemia of stable prematures. To date, EPO has not been shown, convincingly, to alleviate the anemia present early in the life of acutely-ill, premature infants.

ABO-haemolytic Disease of the Newborn (ABO-HDN): Factors Influencing its Severity and Incidence in Venezuela

The objective of this study was to determine the incidence of the Haemolytic Disease of the Newborn due to ABO blood group incompatibility (ABO-HDN) in the population of Caracas attending the Maternity Hospital 'Concepción Palacios'. The relationship between A and B antigens density of cord blood erythrocytes and the cytotoxic activity of antibodies in mothers' sera with the severity of the haemolytic disease, was also studied. From a sample of 245 blood group 'O' mothers, 68 gave birth to full term 'A' or 'B' blood group infants. The evolution of serum bilirubin and the routine haematological values, were followed in all the babies during 72 h after birth, allowing the diagnosis of ABO-HDN in 21 infants. Taking into account that in Venezuela the frequency of blood group 'O' is 59 per cent, it was concluded that in the general population of newborns, 16 per cent present foeto-maternal ABO incompatibility, and the incidence of ABO-HDN was near to 5 per cent. The density of the 'A' and 'B' antigens in cord red cells was studied using an immunoenzymatic assay. No statistically significant association between antigen maturity and severity of the ABO-HDN could be shown. A positive association was found between cytotoxic capacity of mothers' sera and development of ABO-HDN (P < 0.05). Twenty ABO incompatibles children presented moderate late anaemia at 3 weeks of age.

Neonatal anemia: pathophysiology and treatment.

All neonates experience a decline in circulating red blood cell (RBC) mass due to diminished erythropoietin (EPO) levels. This effect is more pronounced in small, premature infants and can lead to severe anemia and need for RBC transfusions--particularly, if repeated phlebotomy is required to monitor acutely-ill neonates. Although optimal RBC transfusion therapy has been a long-term challenge for neonatologists, the emergence of recombinant EPO as promising therapy for neonatal anemia is the major issue for 1994. Accordingly, this report for the 12th International Convocation on Immunology (Transfusion Immunology and Medicine) will focus on this aspect of neonatal transfusion medicine. Although several controlled trials to evaluate EPO as therapy have been completed, definitive answers to all questions regarding efficacy and possible toxicity have not been provided. However, therapy with EPO plus iron and adequate nutrition is likely to be proven effective for the relatively late anemia of stable prematures. To date, EPO has not been shown, convincingly, to alleviate the anemia present early in the life of acutely-ill, premature infants.

Blood transfusion in late anemia of prematurity: effect on oxygen consumption, heart rate, and weight gain in otherwise healthy infants.

In premature infants there is no universally accepted definition of anemia requiring transfusion. We designed the present investigation to study the effects of red blood cell transfusion (based on simple transfusion rules) on weight gain, energy metabolism, and heart rate in otherwise healthy preterm infants. We measured oxygen consumption (VO2), respiratory quotient (RQ) and energy expenditure (EE) by 4-hour indirect calorimetry, and assessed weight gain over 7 days and heart rate in 12 infants with late anemia of prematurity before and after red blood cell transfusion (10 ml/kg). At the time of transfusion, postmenstrual age was 38 +/- 1 weeks (mean +/- SEM), body weight 2.14 +/- 0.13 kg, and hemoglobin concentration 7.7 +/- 0.3 g/dl (range: 5.5-9.2). Red blood cell transfusion increased the hemoglobin concentration by 3.8 +/- 0.5 g/dl, but had no significant effect on weight gain (15.4 +/- 2.4 vs. 13.8 +/- 1.8 g/kg/day), VO2 (8.7 +/- 0.3 vs. 8.7 +/- 0.3 ml/kg/min), minimal VO2 (7.2 +/- 0.3 vs. 7.7 +/- 0.4 ml/kg/min), RQ (0.96 +/- 0.02 vs. 0.95 +/- 0.02), EE (50 +/- 2 vs. 51 +/- 2 kcal/kg/day), and heart rate (160 +/- 3 vs. 158 +/- 3 min-1). We conclude that oxygen supply and energy metabolism were not compromised in the anemic preterm infants at the time of red blood cell transfusion.

Suppression of erythropoiesis by intrauterine transfusions in hemolytic disease of the newborn: Use of erythropoietein to treat the late anemia

Hemolytic disease of the fetus and newborn has three phases of anemia: in utero, in the first week of life, and in the weeks and months after birth. Intrauterine transfusions can ameliorate the severity of both fetal and early anemia, but late anemia and the need for transfusion remain significant problems. Bone marrow hypoplasia--probably a result of suppression of erythropoiesis from the intrauterine transfusions--was documented in the three patients tested in our study. Because erythropoietin (EPO) levels have been found to be low (i.e., normal) in these previously transfused patients despite the degree of anemia, we treated four affected infants with EPO, 200 microliters/kg subcutaneously three times a week, and noted reticulocytosis and increased hemoglobin values 2 to 4 weeks later. One patient again had reticulocytopenic anemia when the EPO therapy was stopped but responded to retreatment. Our study indicates that EPO treatment may be effective in the management of late anemia and could help to decrease the need for postnatal transfusions.

Regional transfusion centre preoperative autologous blood donation programme: the first two years.

To assess the efficacy of a regional autologous blood donation programme. Clinical and laboratory data were collected and stored prospectively. Transfusion data were collected retrospectively from hospital blood bank records. Northern Region Blood Transfusion Service and 14 hospitals within the Northern Regional Health Authority. 505 patients referred for autologous blood donation before elective surgery. Patient eligibility, adverse events from donation, autologous blood units provided, and autologous and allogeneic blood units transfused within 10 days of operation. Of 505 patients referred, 354 donated at least one unit. 78 of 151 referred patients who did not donate were excluded at the autologous clinic, mostly because of anaemia or ischaemic heart disease. In 73 cases the patient, general practitioner, or hospital consultant decided against donation. 363 autologous procedures were undertaken. In 213 (59%) cases all requested units were provided. The most common reasons for incomplete provision were late referral or anaemia. Adverse events accompanied 24 of 928 donations (2.6%). Transfusion data were obtained for 357 of the 363 procedures. 281 donors were transfused; autologous blood only was given to 225, autologous and allogeneic blood was given to 52, and allogeneic blood only was given to four. 648 of 902 (72%) units of autologous blood were transfused. Complete provision of requested autologous units was followed by allogeneic transfusion in 12 of 208 procedures (5.8%). Incomplete provision was followed by allogeneic transfusion in 44 of 149 procedures (30%). This study shows the feasibility of a regional autologous transfusion programme. Autologous donors only infrequently received allogeneic transfusion. Patients should be appropriately selected and referred early.

Recombinant Erythropoietin as Treatment for the Late Hyporegenerative Anemia of Rh Hemolytic Disease

Infants with Rh hemolytic disease can develop a "late" anemia characterized by low serum concentrations of erythropoietin but erythroid progenitors that remain highly erythropoietin-responsive. Erythropoietin administration was evaluated in two patients as an alternative to transfusion. Reticulocyte counts increased after 5 days of treatment, and hematocrits increased after 10 days. Neither patient received erythrocyte transfusions following erythropoietin therapy.

Late hyporegenerative anemia in Rh hemolytic disease

Late hyporegenerative anemia in Rh hemolytic disease

Anemia Tardía en Niños con Incompatibilidad Rh y ABO

Dres.: Manuel Olivares G. ; Liliana Schlesinger F. ; Ernesto Ri'os L.Ines Lopez T.; Abraham Stekel G. .Late Anemia in Infants With RhABO IncompatibilitiesThe spontaneous evolution of the hematocrit, hemoglobin and reticulocyte count values of 131 term infants\vith clinical and laboratory diagnosis of Rh or ABO incompatibility was studied. They vere classified as follows: 17infants with Rh incompatibility not subject to exchange transfusion, 36 infants with Rh incompatibility requiringone exchange transfusion, 17 infants with Rh incompatibility requiring two or more exchange transfusions, 15infants with ABO incompatibility who dis not require exchange transfusion and 46 infants with ABO incompati-bility who did not require exchange transfusion. Thirty five normal infants served as controls. Hematological valueswere determined at 15, 30, 45, 60, 90, 180 and 270 days of age. Significant differences were present at 15, 30 and60 days of age between normals and patients with incompatibility. Despite the disadvantage in hematocrit andhemoglobin concentration experienced at birth and up to three month of age by infants with incompatibility,differences disappear between 90 and 180 days of age. This is important in planning the treatment of the exageratedphysiologic of these patients.Un numero significative de los nifios con En la terapia de esta se utiliza aenfermedad hemoh'tica del recien nacido, desa- menudo la transfusion sangufnea, sometiendo alrrollan en las primeras semanas de vida, lo que se nino a los riesgo&ifthejeates a este procedimientoha denominado anemia tardia-

Iron in the preterm infant: A pilot study comparing Fe 2+ and Fe 3+ tolerance and effect

IRON SUPPLEMENTATION is universally recognized as a means of preventing late anemia in preterm infants. ~,2 However, some disagreement is apparent concerning the type and timing of iron supplementation. A common recommendation in Sweden is to start oral administration of iron at age 6 weeks, and to continue for at least 6 months. The accepted regimen is ferrous succinate (Fe 2+) with ascorbic acid in a daily dose of about 10 mg elemental iron. Side effects seem not unusual, mainly consisting of gastrointestinal tract disorders such as colic and constipation, sometimes to such a degree that medication is discontinued by the parents. Iron chelate with nonionized Fe 3+ is an iron preparation said to be nonconstipating. Given in this form, the iron is made available for absorption after destruction of the chelation and reduction of Fe 3+ to Fe 2§ in the gastrointestinal tract? Because these processes are not complete it is recommended that three times the dose of elemental iron be given if ferric rather than ferrous iron is used. This study was designed to compare efficiency and side effects of two such preparations in recommended doses, and specifically, whether Fe 3+ (Irostrene) could be used alternatively when side effects of Fe z+ (Ferromyn) prevent proper medication.

Late onset pyridoxine-responsive sideroblastic anemia after bone marrow transplantation

Late onset pyridoxine-responsive sideroblastic anemia after bone marrow transplantation

Late anaemia in infants with rhesus haemolytic disease treated with intensive phototherapy.

The purpose of the present study was to determine the incidence of late anaemia in infants with rhesus haemolytic disease (RHD) who had received intensive phototherapy. Sixty infants with RHD and with strongly positive direct Coombs' tests who had received intensive phototherapy (blue double light) were followed as out-patients with regard to development of late anaemia. Fifteen (25%) infants developed moderate anaemia and 5 (8%) severe anaemia, one of the latter requiring a blood transfusion. The incidence of late anaemia was equal in "non-exchanged" infants and those who required exchange transfusion. The former developed anaemia significantly earlier than the latter, and in both groups the declining Hb level caused a marked reticulocyte response which was equal in both groups. This response may explain the low incidence of anaemia in both the "non-exchanged" and "exchanged" infants. From the present study and previous investigations it can be concluded that phototherapy, especially intensive phototherapy, is of great value in the treatment of rhesus haemolytic disease.

Erythroblastosis fetalis due to anti-S antibody

<h2>Summary</h2> Hemolytic disease of the newborn infantdue to isosensitization by the S blood group factor in an Rh-positive mother resulted in postnatal hyperbilirubinemia and a "late anemia" syndrome in the infant. In our case, as well as in two of the three previously reported cases, the isosensitized pregnancy followed previous blood transfusions.

Phototherapy—A Note of Caution

A newborn infant with Rh hemolytic disease developed profound anemia following phototherapy. The potential danger of the use of phototherapy in hemolytic disease of the newborn is discussed. Since the development of late anemia following erythroblastosis fetalis occasionally occurs, the need for frequent repeated hemoglobin levels in infants with hemolytic disease of the newborn is stressed.

Indication et résultats de l'abstention thérapeutique immédiate dans la maladie hémolytique du nouveau-né due au facteur Rh

No immediate therapy was applied to 228 cases of haemolytic disease of the newborn (Rh) diagnosed at birth. In 189 infants, cord haemoglobin was equal or superior to 13–5 g/100 ml and cord serum bilirubin equal or inferior to 3 mg/100 ml ; in 39 infants, one of these two values was less favourable. Three indications for secondary therapy are tentatively put forward ; early hyperbilirubinaemia above a line joining 8 mg at 18 hr to 18 mg at 48 hr, late hyperbilirubinaemia above 20 mg from the third day on, and late anaemia when haemoglobin concentration falls below a line joining 10 g at two weeks to 8,5 g at seven weeks. These two last indications appear less closely related to cord blood data, but much more to previous history and prematurity ; however except for these two circumstances, cord blood criteria retain their full importance. Taking into consideration that immediate exsanguino-transfusion at birth is required when probability for secondary therapy is 50 % or more, the Authors propose : - to reject initial postponement in infants whose previous siblings were treated for haemolytic disease (Rh) or were affected with deep neo-natal jaundice of whatever origin, as well as in infants born more than two weeks before term, - to estimate in other infants, the probability for late therapy by doubling the ratio B 3 /Hb 2 , and to remain expectative at birth when the result is inferior to 0,50.