Maternal red blood cell alloimmunization requiring intrauterine transfusion: a comparative study on management and outcome depending on the type of antibody.

BACKGROUND: The antibody primarily responsible for fetal anemia may influence treatment and prognosis. The primary objective was to compare ante- and postnatal management and the outcomes of maternal red blood cell (RBC) alloimmunizations according to the antibody involved. The secondary objective was to compare anti-D alloimmunizations according to associated number of antibodies. STUDY DESIGN AND METHODS: A single-center study from 1999 to 2015 including maternal RBC alloimmunizations requiring intrauterine transfusion (IUT) was conducted. Patients were classified according to the antibody involved: anti-D, other Rh (anti-c and anti-E), and anti-K1. Obstetric data, IUT characteristics, and neonatal outcome were compared. A specific study on the anti-D, when isolated or associated, was then conducted. RESULTS: There were 106 pregnancies included, with 77.4% having anti-D, 9.4% having another anti-Rh (Rh group), and 13.2% having anti-K1. No significant difference between the anti-D and Rh groups was found for management and prognosis. The hemoglobin level in the first IUT was higher in the anti-D group than in the Kell group (6.8 vs. 4.7 g/dL, p = 0.008). Newborns in the anti-D group had significantly higher bilirubin levels and phototherapy duration than those in the Kell group. The mean estimated daily decrease in hemoglobin and that between the first two IUTs were lower with an isolated anti-D, compared with anti-D associated with two antibodies (p = 0.04). CONCLUSION: Anti-K1 alloimmunizations seem to cause more severe fetal anemia than anti-D alloimmunizations. Moreover, a decrease in hemoglobin appears to be more rapid when anti-D is associated with other antibodies.

Successful management of severe hemolytic disease of the fetus due to anti-Jsb using intrauterine transfusions with serial maternal blood donations: a case report and a review of the literature.

BACKGROUND: The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. CASE REPORT: A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. STUDY DESIGN AND METHODS: The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). RESULTS: Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. CONCLUSION: This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.

EDTA glycine acid treatment of red blood cells.

IgG dissociation is necessary when a sample is direct antiglobulin test (DAT) positive and antigen testing using blood grouping serum reactive by the antiglobulin test is performed. Exposure of IgG-coated red blood cells (RCBs) to a low pH of 3.0 with EDTA glycine acid successfully dissociates the IgG, rendering the RCBs DAT negative 82 to 85 percent of the time. The procedure takes one minute or less and leaves RBC antigens intact and able to be typed except for those antigens in the Kell blood group system and for the high-prevalence antigen Er(a).

Exchange transfusions and top-up transfusions in neonates with Kell haemolytic disease compared to Rh D haemolytic disease.

OBJECTIVE: To evaluate neonatal outcome in Kell haemolytic disease compared to Rh D haemolytic disease. STUDY DESIGN: Retrospective study of all (near)-term neonates with Kell (n=34) and Rh D haemolytic disease (n=157) admitted to our centre between January 2000 and December 2008. We recorded the need for exchange transfusion and top-up transfusions up to 3 months of age. RESULTS: Neonates in the Kell group required less days of phototherapy than neonates in the Rh D group [2.4 vs. 4.1 days, respectively (P<0.01)]. The percentage of neonates requiring an exchange transfusion was lower in the Kell group than in the Rh D group [6% (2/34) and 62% (98/157), respectively (P<0.01)]. The percentage of neonates in the Kell group and Rh D group requiring a top-up transfusion was 62% (21/34) and 72% (113/157), respectively (P=0.20). The median number of top-up transfusions per neonate in the Kell group and Rh D group was 1 [interquartile range (IQR) 0-2] and 2(IQR 0-2), respectively (P=0.07). CONCLUSION: Neonates with Kell haemolytic disease require less phototherapy and less exchange transfusions compared to neonates with Rh D haemolytic disease, but an equal number of top-up transfusions.

Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. STUDY DESIGN AND METHODS: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. RESULTS: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. CONCLUSION: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

Serial blood donations for intrauterine transfusions of severe hemolytic disease of the newborn with the use of recombinant erythropoietin in a pregnant woman alloimmunized with anti-Ku.

BACKGROUND: The management of a pregnant woman with the rare Ko phenotype and anti-Ku is a special challenge, because matched blood is extremely rare and the possibility of severe hemolytic disease of the newborn is high. CASE REPORT: A 30-year-old woman with rare Ko (Knull) phenotype presented at 18 weeks of gestation with positive indirect agglutination test results. She had anti-Ku due to previous blood transfusion, one pregnancy, and two abortions. STUDY DESIGN AND METHODS: During this pregnancy, anti-Ku titers ranged from 1024 to 4096. At the 26th week of gestation ultrasound showed a hydropic fetus and urgent intrauterine exchange transfusion was performed with the maternal red blood cells (RBCs). Recombinant human erythropoietin (rHu-EPO) and intravenous (IV) iron were administered to the mother to ensure an adequate supply of matched RBCs for intrauterine transfusions and possible perinatal hemorrhage. RESULTS: Intrauterine transfusions were repeated every 1 to 3 weeks. By 35 weeks 2 days of gestation, the mother had donated 4 units of blood, and four intrauterine transfusions had been performed. Cesarean section was then decided and a healthy male newborn was born. He was treated with phototherapy but without exchange transfusions. By the 15th day of life rHu-EPO was administrated to the newborn because of anemia. The maternal RBCs completely disappeared from the child's blood by Day 100. CONCLUSIONS: As shown in this case, treatment with rHu-EPO and IV Fe has effectively increased the mother's capacity to donate RBCs for autologous use and intrauterine transfusions, with no adverse effects to the mother or the child.

Treatment of hemolytic disease of the newborn caused by anti-Kell antibody with recombinant erythropoietin.

Recent data suggest that antibody-mediated suppression of erythroid progenitors may contribute to the anti-Kell-induced alloimmune hemolytic disease of the newborn (HDN). A 32-week-old girl who was positive for Kell was born to a mother who was negative for Kell but known to have anti-Kell antibodies. After birth, the baby had HDN and hyperbilirubinemia develop (peak bilirubin 21 mg/dL at day 9 of life). which was treated with phototherapy. Although the hyperbilirubinemia resolved, she became progressively anemic (hematocrit 22%) with an inappropriately low reticulocyte response (1.1%) and erythropoietin (EPO) level (20 mU/mL). To avoid the need for a blood transfusion, she was treated with recombinant erythropoietin (rEPO) and oral iron supplements. One week after starting EPO, the reticulocyte count increased to 9.1%. Erythropoietin therapy was continued for a total of 9 weeks, with resolution of her anemia at the end of therapy (hematocrit 35%). Thus, we were able to successfully treat the anemia with rEPO with avoidance of blood transfusion. This patient demonstrates that the antibody-mediated erythroid suppression in Kell alloimmune anemia can be overcome by rEPO. Recombinant erythropoietin should therefore be considered in the management of infants with severe or hypoproliferative anti-Kell-associated anemia.

The clinical outcome of non-RhD antibody affected pregnancies in Northern Ireland.

We assessed the clinical outcome of pregnancies with non-Rh-D antibody in Northern Ireland using retrospective case note review. During the study period (April 1999- March 2000) 186 women with clinically significant antibodies were identified from the records of the antenatal laboratory of the Northern Ireland Blood Transfusion Service. Eighty-five women were included in the study using the criteria mentioned above. None of the fetuses required intrauterine transfusion during this period. One baby required exchange transfusion, three were given top-up transfusions and 17 had phototherapy. Nine babies with a positive direct antiglobulin test (DAT) received no treatment. The incidence of anti-Kell could be reduced by transfusing Kell negative red cells to premenopausal women. It is important that all pregnant women are tested at least twice in their pregnancy to detect the antibodies formed late in the pregnancy. It is useful to formulate a standard protocol for antenatal interventions. Non Rh-D antibodies can cause significant anaemia for up to six weeks in the neonatal period, hence early detection of maternal antibodies is important so that the neonates are followed up for an appropriate length of time.

[Hemolytic disease of the newborn and irregular blood group antibodies in the Netherlands: prevalence and morbidity]. / Hemolytische ziekte van de pasgeborene en irregulaire-bloedgroepantagonisme in Nederland: prevalentie en morbiditeit.

OBJECTIVE: To inventory prevalence and morbidity of haemolytic disease of newborn caused by irregular anti-erythrocyte antibodies other than antirhesus-D. DESIGN: Prospective registration study. METHOD: All paediatricians (n = 380) in general hospitals and contact persons (n = 79) in university hospitals were asked for monthly reports of clinical cases of haemolytic disease of newborn during 2 years (1996-1997). RESULTS: Response was 97%. A total of 130 reports were received in two study years, 49 of which could not be confirmed as non-RhD-non-AB0 antagonism. In the group of which the transfusion history was known (n = 60), 29 pregnant women (48%) had received transfused blood at some time. Of the antibodies found, anti-c, anti-E and anti-K were the most frequent. The direct antiglobulin test was positive in 61 of the 81 cases, negative in 10 cases, while in 10 cases it was unknown or false-negative due to earlier intrauterine transfusions (in three neonates). The highest bilirubin levels recorded were 572, 559 and 520 mumol/l (all three with maternal anti-c antagonism). Therapeutic data were known concerning 80 of the 81 newborn: 21 (16%) received no treatment, 24 (29%) only phototherapy and the others--in addition to phototherapy if any--also blood transfusion, exchange transfusion or intrauterine transfusion, or a combination of these. CONCLUSION: It was calculated that the actual prevalence of irregular anti-erythrocyte antibodies in Dutch pregnant women probably amounts to approximately 0.25%. This finding may possibly be confirmed since starting 1 July 1998 all pregnant women in the country are screened for the presence of these antibodies. It is recommended that girls and women in the reproductive age group should receive primary prevention of development of irregular anti-erythrocyte antibodies by application of a selective blood transfusion policy, taking into account the occurrence of the antigens c, E and K.

Red cell antibodies in pregnancy: there is no 'critical titre'.

The purpose of this study was to determine the predictive value and reliability of using a 'critical titre' when assessing the ability of red cell alloantibodies to cause haemolytic disease of the newborn. Titration studies and clinical follow-up of 418 antenatal cases where the mothers had red cell antibodies were studied retrospectively. The antibody specificities were anti-D (n = 359), anti-c (n = 34), anti-E (n = 19) and anti-K (n = 6). Depending on the titre being lower or higher than 16 in the indirect antiglobulin test, the severity of disease was established on the given therapy. Anti-D antibodies with a titre 16 were present in 20% of all cases associated with transfusion need of the child; for anti-c, -E and -K the figure was 4%. Titres > or = 16 resulted in both groups in 50% of the cases in phototherapy only, or no therapy at all. Titres are therefore not reliable indicators for predicting the severity of haemolytic disease of the newborn. Neither should they be used as a guide to whether or not antenatal intervention is indicated. Alternative quantitative or functional assays that measure cytotoxic lysis or phagocytosis or a combination of both should be performed instead.

First case of hemolytic disease of the newborn due to anti-Ula antibodies.

The first case of hemolytic disease of the newborn (HDN) due to anti-Ula antibodies is described. The infant had severe anemia with a positive direct antiglobulin test with anti-IgG that required blood transfusion. But jaundice was not severe enough for exchange transfusion or phototherapy.

The significance of anti-Kell sensitization in pregnancy.

In a 10-year period, 407 of 350,000 pregnancies showed maternal anti-Kell allo-immunization, i.e., an incidence of 1.16 per 1000 pregnancies. About 88% of Kell immunized women gave a history of previous transfusion. There were 51 pregnancies with Kell positive partners (all Kk) resulting in 10 Kell positive babies, of whom six had a positive direct antiglobulin test (DAGT). There were two stillbirths due to haemolytic disease of the newborn, when the maternal anti-Kell titres were 1/256. One baby was severely anaemic and given a top-up transfusion, and two babies were jaundiced and given phototherapy. A policy for management of Kell sensitized pregnancies is outlined, based upon maternal anti-Kell titre and where appropriate fetal blood sampling.

Kell sensitization in pregnancy.

Maternal anti-Kell antibody was found in 127 of 127,076 pregnancies during a 16-year period (0.1%). Thirteen Kell-sensitized pregnancies ended with a Kell-positive newborn infant, five of these had a poor perinatal outcome (hydrops, intrauterine or neonatal death, hemoglobin less than 7.9 gm, congestive heart failure). Mothers with Kell-positive infants and poor outcome had anti-Kell titers greater than or equal to 1:128 at delivery. With a maternal anti-Kell titer less than 1:32 at delivery, only one baby was Kell positive and mildly affected by hemolytic disease. Spectrophotometric analysis of amniotic fluid (delta optical density at 450 nm) in three of four pregnancies with poor perinatal outcomes revealed values of delta optical density at 450 nm in the high midzone of Liley within 1 week of delivery. Therefore, Kell-sensitized patients have to be managed differently from patients with rhesus sensitization. A management scheme to optimize perinatal outcome in Kell-sensitized pregnancy is described on the basis of this largest reported series of Kell-sensitized pregnancies.