Jk3 alloantibodies during pregnancy-blood bank management and hemolytic disease of the fetus and newborn risk.

BACKGROUND: The Kidd-null phenotype, Jk(a-b-), occurs in individuals who do not express the JK glycoprotein. Jk(a-b-) individuals can make an antibody against the Jk3 antigen, a high-incidence antigen present in more than 99.9% of most populations. This presents many challenges to the blood bank including identification of the antibody, masking of other antibodies, and how to provide transfusion support given the rarity of Jk3-negative blood products. Kidd antibodies may cause acute and delayed hemolytic reactions as well as hemolytic disease of the fetus and newborn (HDFN). In this article, we present a series of four practical cases of pregnant women with the anti-Jk3 alloantibody that demonstrate a range of clinical presentations of Kidd-related HDFN. STUDY DESIGN AND METHODS: We retrospectively reviewed the clinical and blood bank records for four patients and their newborns encountered at institutions in Tennessee, Missouri, Hawaii, and Guam with an anti-Jk3 identified during pregnancy. RESULTS: Two cases showed no significant evidence for HDFN, while two cases were of mild-to-moderate severity requiring early delivery due to elevated middle cerebral artery (MCA) flow velocities but requiring only phototherapy for hyperbilirubinemia. No intrauterine or neonatal transfusions were necessary. Anti-Jk3 alloantibody titers ranged from 2 to 128. CONCLUSION: Clinical manifestations of anti-Jk3 HDFN are generally mild to moderate. Anti-Jk3 titers were not found to correlate directly with HDFN severity. We suggest a titer of 16 to 32 as a cutoff for implementing enhanced monitoring of fetal MCA flow velocities, as such titers may be indicative of elevated HDFN risk.

Blood transfusion risks and alternative strategies in pediatric patients.

Although the safety of the blood supply has been greatly improved, there still remain both infectious and noninfectious risks to the patient. The incidence of noninfectious transfusion reactions is greater than that of infectious complications. Furthermore, the mortality associated with noninfectious risks is significantly higher. In fact, noninfectious risks account for 87-100% of fatal complications of transfusions. It is concerning to note that the majority of pediatric reports relate to human error such as overtransfusion and lack of knowledge of special requirements in the neonatal age group. The second most frequent category is acute transfusion reactions, majority of which are allergic in nature. It is estimated that the incidence of adverse outcome is 18:100,000 red blood cells issued for children aged less than 18 years and 37:100,000 for infants. The comparable adult incidence is 13:100,000. In order to decrease the risks associated with transfusion of blood products, various blood-conservation strategies can be utilized. Modalities such as acute normovolemic hemodilution, hypervolemic hemodilution, deliberate hypotension, antifibrinolytics, intraoperative blood salvage, and autologous blood donation are discussed and the pediatric literature is reviewed. A discussion of transfusion triggers, and algorithms as well as current research into alternatives to blood transfusions concludes this review.

Management of anti-Jka alloimmunization.

OBJECTIVE: To determine whether prenatal management using guidelines established for anti-D is applicable to anti-Jka. STUDY DESIGN: A computerized database containing the records of all alloimmunized pregnancies at The Ohio State University Medical Center with due dates from 1959 to 2008 was used to identify pregnancies affected only by anti-Jka. Only cases with evidence that the newborn was Jka antigen positive were included. RESULTS: Twenty affected pregnancies met inclusion criteria. Of those, 16 pregnancies required monitoring with serum titers only and 4 were followed with more diagnostic tests as recommended during that time period. One pregnancy with the highest titer of 32 and elevated middle cerebral artery peak systolic velocity (MCA PSV) required 4 intrauterine transfusions for fetal anemia. Another pregnancy with a titer of 32 had an infant who required phototherapy for hemolytic disease of the fetus/newborn (HDFN), with a hemoglobin value of 15.9 g/dL. None of the other 18 infants required any therapy for HDFN. CONCLUSION: Our case series identified severe disease in 1 of 20 pregnancies from anti-Jka using maternal antibody titer and MCA PSV. Criteria used for monitoring RhD alloimmunization were effective in detecting severe HDFN resulting from to anti-Jka.

[A case of severe hemolytic disease of the newborn due to anti-Dia antibody].

Here we report a severe case of hemolytic anemia of the newborn with kernicterus caused by anti-Di(a) antibody. A full term male infant was transferred due to hyperbilirubinemia on the third day of life. Despite single phototherapy, the baby's total bilirubin had elevated to 30.1 mg/dL. After exchange transfusion, total bilirubin decreased to 11.45 mg/dL. The direct antiglobulin test on the infant's red cells was positive. The maternal and infant's sera showed a negative reaction in routine antibody detection tests, but were positive in Di(a) panel cells. The frequency of the Di(a) antigen among the Korean population is estimated to be 6.4-14.5%. Anti-Di(a) antibody could cause a hemolytic reaction against transfusion or hemolytic disease of the newborn. We suggest the need for reagent red blood cell panels to include Di(a) antigen positive cells in antibody identification test for Korean.

A Case of Severe Hemolytic Disease of the Newborn Due to Anti-Di(a) Antibody / 대한진단검사의학회지

Here we report a severe case of hemolytic anemia of the newborn with kernicterus caused by anti-Di(a) antibody. A full term male infant was transferred due to hyperbilirubinemia on the third day of life. Despite single phototherapy, the baby's total bilirubin had elevated to 30.1 mg/dL. After exchange transfusion, total bilirubin decreased to 11.45 mg/dL. The direct antiglobulin test on the infant's red cells was positive. The maternal and infant's sera showed a negative reaction in routine antibody detection tests, but were positive in Di(a) panel cells. The frequency of the Di(a) antigen among the Korean population is estimated to be 6.4-14.5%. Anti-Di(a) antibody could cause a hemolytic reaction against transfusion or hemolytic disease of the newborn. We suggest the need for reagent red blood cell panels to include Di(a) antigen positive cells in antibody identification test for Korean.

Use of a PCR-based assay for fetal Cw antigen genotyping in a patient with a history of moderately severe hemolytic disease of the newborn due to anti-Cw.

Anti-Cw is an uncommon cause of clinically significant hemolytic disease of the newborn (HDN). We report an unusually severe case of HDN due to anti-Cw that required phototherapy and exchange transfusion. We also describe a novel PCR-RFLP method for Cw typing of fetal genomic DNA that was used for prenatal diagnosis in a subsequent pregnancy. Following PCR amplification of a 163 bp segment of the RHCE gene containing the nucleotide 122 G to A substitution that corresponds to the Cw allele, Cw types were distinguished by TaqI digestion. PCR-RFLP analysis confirmed that the father and previously affected child were Cw-positive. The fetus was Cw-negative, thus excluding HDN in the current pregnancy and obviating the need for further invasive or noninvasive diagnostic procedures for the remainder of the pregnancy. This case illustrates the utility of PCR-based fetal genotype determination in pregnancies at risk of HDN due to uncommon red cell antibodies such as anti-Cw.

Anti-U and haemolytic disease of the fetus and newborn.

The red cell alloantibody, anti-U, is uncommon but is a recognised cause of haemolytic disease of the fetus and newborn. We describe six pregnancies complicated by the presence of maternal anti-U, and review nine other well-documented cases. In these 15 cases severe haemolytic disease occurred only with titres of > or = 1/512, and titres as high as 1/4000 were not necessarily associated with significant haemolysis. We recommend that an anti-U titre of > or = 1/128 or more at > or = 17 weeks of gestation is an indication for assessment of haemolysis in the fetus. Amniocentesis is the preferred initial investigation.

Concentration of anti-D antibodies in Rh(D) alloimmunized pregnant women, as a predictor of anemia and/or hyperbilirubinemia in their newborn infants.

OBJECTIVES: To define a simple, safe and reliable program for the monitoring of anti-D alloimmunized pregnancies by analysis of the covariation between antenatal values of the titer and the concentration of anti-D antibodies in maternal serum, the deltaOD(450 nm) in amniotic fluid samples, and the levels of B-hemoglobin and S-bilirubin in the newborns at birth. SUBJECTS: Ninety-three Rh(D) negative women with anti-D antibody titers > or = 16 who, after the completed 34th gestational week, gave birth to Rh(D) positive babies with a positive direct antiglobulin test. METHODS: The titers and the concentrations of anti-D antibodies in maternal serum were determined by standard procedures every second week from the 25th week of gestation. In 47 of the 93 women, deltaOD(450 nm) in amniotic fluid was determined at least once. All antenatal values used in the study were determined within 14 days before delivery. RESULTS AND CONCLUSION: Maternal serum antibody titers < or = 32 or > or = 1000 could in themselves well predict unaffected and affected newborns. Antibody titers between 64 and 512 could not accurately predict newborns with or without hemolytic disease. As a complementary monitoring test, determination of the deltaOD(450 nm) was found to be less accurate when compared to determination of the concentration of anti-D antibodies. In order to monitor Rh(D) alloimmunized pregnancies, determination of the concentration of anti-D antibodies may possibly replace determination of deltaOD(450 nm).

Diagnostic testing during pregnancy: a descriptive analysis of utilisation data.

To describe patterns of diagnostic testing during the antenatal period and to assess the potential benefit of using Medicare claims data in monitoring testing practice, we examined the matched claims data (with identifying details removed) on approximately 10,000 women having a confinement for which a Medicare benefit was claimed between 1 July and 30 September 1990. The results showed that almost all the women included in the study sample had an ultrasound and blood group and antibody examination. A smaller proportion had serological tests for syphilis (77 per cent), rubella (51 per cent) and hepatitis B carriage (73 per cent). Two-thirds had urine microscopy and culture, and under half (40 per cent) had serum alpha-fetoprotein estimation. Few (18 per cent) had a claim processed for microscopy and culture of a genital swab and fewer than 8 per cent claimed for any other pathology tests. There were differences in the proportions having tests, depending on whether the clinician managing the confinement was a specialist obstetrician or a general practitioner, and depending on geographic area and age group. While the data do not represent all women having a confinement in New South Wales, the selective use of antenatal diagnostic tests found in this study is of considerable public health importance and analysis of claims data can provide useful information for health professionals.

[A case of dissecting aortic aneurysm and presence of anti-Jr(a) antibody].

A 66-year-old woman was diagnosed as a DeBakey type II dissecting aortic aneurysm with angiography and CT. Antibody screening revealed circulating anti-Jr(a) antibody. Preoperatively, erythropoietin was administered twice a week. Over 24 days, a total of 1200 ml of her blood was removed and stored for autologous transfusion. The dissecting ascending aorta was replaced with the aid of cardiopulmonary bypass. The post operative course was uneventful. By using erythropoietin, pre-donated autologous blood, cell saver, aprotinin and transfusion of fresh autologous blood, it was possible to perform cardiovascular surgery on this patient who had an abnormal antibody. This patient is the first case of repair or dissecting aortic aneurysm with anti-Jr(a) antibody in Japan.

Alloantibodies against A and B blood types in cats.

This study characterizes the naturally occurring feline alloantibodies against A and B blood type. All examined type-A and type-B cats had naturally occurring antibodies against erythrocytes of the opposite blood type. In order to determine the class of immunoglobulins, sera from cats were analyzed using incubation with 2-mercaptoethanol (2-ME), immunoprecipitation, and gel filtration. Type-A cats had weak agglutinins of the IgM class and weak hemolysins which consisted of approximately equal parts of IgG and IgM class. Type-B cats had strong hemagglutinins and hemolysins mostly of the IgM class. Colostral antibodies were detectable in newborns as early as 4 h after birth and their own alloantibody production started at 6-8 weeks of age. The presence of naturally occurring alloantibodies, in particular the anti-A alloantibodies, renders cats susceptible to clinical incompatibility reactions.

Use of recombinant human erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease.

We treated a patient with alcohol-induced cirrhosis, intractable pain from a defective hip prosthesis, and multiple red cell allo-antibodies with recombinant human erythropoietin (EPO) in order to facilitate collection of blood for autologous transfusion during an elective total hip revision. This patient had experienced a delayed transfusion reaction 4 months earlier after receiving least incompatible packed red cells for gastrointestinal bleeding. His blood could not be crossmatched because of the development of multiple antibodies to homologous blood given during previous surgery and several episodes of gastrointestinal hemorrhage. Following initiation of EPO therapy, there was a prompt and persistent increase in the reticulocyte count from a baseline of 1.6% to a maximum of 8.6%. This was accompanied by maintenance of the hematocrit between 32% and 38.5% despite withdrawal of seven units of autologous blood over the 45-day treatment period. Poor venous access and availability of blood bank personnel, not hematocrit level, were the limiting factors that determined how frequently blood could be collected. We conclude that EPO stimulated erythropoiesis in this patient with underlying anemia of chronic disease and facilitated harvest of autologous blood for elective surgery.

Rh immunization by the partial D antigen of category DVa.

Reported here is the first example of a partial D antigen stimulating the production of anti-D: stimulation was of fetal origin. During her second pregnancy, anti-D developed in the serum of a D-negative mother who had received Rh immunoglobulin after the birth of her first D-positive child. Her second baby had moderate neonatal jaundice and was successfully treated by phototherapy. Subsequently the red cells of the father and of the first child were shown to carry a partial D antigen of category DVa type. Six available batches of Rh immunoglobulin reacted with DVa cells.

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.

Structural variability of the neutral carbohydrate moiety of cow colostrum kappa-casein as a function of time after parturition. Identification of a tetrasaccharide with blood group I specificity.

New neutral oligosaccharides from cow colostrum kappa-casein were identified and characterized by 500-MHz 1H-NMR spectroscopy. Their structures are Gal beta(1----3)GalNAc-ol, Gal beta(1----3)[GlcNAc beta(1----6)]GalNAc-ol, Gal beta(1----3)[Gal beta(1----4)GlcNAc beta(1----6)]GalNAc-ol, Gal beta(1----3)[Fuc alpha(1----3)[Gal beta(1----4)]GlcNAc beta(1----6)]GalNAc-ol. The tetrasaccharide and the cow colostrum kappa-caseinoglycopeptide which contains this oligosaccharide inhibit the hemagglutination of blood group I human erythrocytes. In cow mature milk only the disaccharide is characterized. The variability of these neutral oligosaccharides in cow kappa-casein as a function of time after calving is studied.

Standardization of bromelin for use in routine one-stage antibody screening.

A simple standardization method for bromelin used in routine one-stage antibody screening is described. Bromelin proteinase activity was assayed using casein as the substrate, and converted to units. The use of proteinase activity units for standardization of bromelin resolves differences between commercial preparations.

Screening for neonatal isohemolytic anemia in calves.

Anti-erythrocytic immunoglobulins in serum and colostrum of 124 anaplasmosis-vaccinated cows were detected with a saline agglutination test. Positive results were correlated with the occurrence of neonatal isohemolytic anemia (NIA) in calves and were used to predict the occurrence of NIA. The disease was prevented by withholding colostrum from calves with a high potential for NIA.