A Rare Case of Hemolytic Disease of the Fetus and Newborn Caused by Anti-s Antibody in a Chinese Patient.

BACKGROUND: Anti-s is a rare alloantibody, and the reported cases of hemolytic disease of the fetus and newborn (HDFN) caused by anti-s are limited to non-Asian populations. METHODS: Here, we report the case of a Chinese woman with a history of multiple pregnancies who developed an alloantibody with anti-s specificity. RESULTS: Her newborn developed HDFN caused by anti-s but the clinical symptoms were not serious. After supportive treatment and bilirubin light phototherapy, the baby was discharged with a good prognosis. CONCLUSIONS: This is the first reported case of anti-s-induced HDFN in a Chinese patient, highlighting the need for further research in the Asian population.

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.

Prevalência de aloimunização eritrocitária em pacientes portadores de anemia falciforme / Prevalence of red blood cell alloimmunization in patients with sickle cell anemia

Embora as transfusões de concentrado de hemácias sejam importantes para o tratamento de pacientes com anemia falciforme, elas acarretam riscos imunológicos tais como a aloimunização a antígenos eritrocitários. Aproximadamente 50% dos pacientes de anemia falciforme recebem transfusões no decorrer da vida, e entre 5% a 10% destes pacientes são submetidos a um programa de transfusão crônica. A aloimunização eritrocitária é uma complicação séria da transfusão, mas relativamente comum. Esta condição pode inclusive levar a reações transfusionais hemolíticas tardias e contribuir para aumentar as comorbidades da doença. Importantes medidas para prevenção destas complicações nestes pacientes são o uso de hemácias previamente fenotipadas, além da fenotipagem do próprio receptor de concentrado de hemácias, determinando seu correto perfil fenotípico e possibilitando a escolha de concentrado de hemácias com antígenos correspondentes ao do paciente a ser transfundido. Extensa genotipagem eritrocitária profilática para selecionar doadores para pacientes que receberão repetidas transfusões durante um longo período é uma aplicação atraente de tipagem de sangue baseados em DNA. Isto é, particularmente relevante para pacientes com doença falciforme onde a taxa de aloimunização é elevada.

Although packed red blood cells transfusions are important for treating patients with sickle cell anemia, this intervention may lead to immunological disturbs, such as alloimmunization by erythrocyte antigens. Approximately 50% of patients with sickle cell anemia receive blood transfusions during their life span, and about 5 to 10% of them require a chronic transfusion scheme. The red blood cell alloimmunization is a serious but common transfusion reaction. This condition could lead to delayed hemolytic transfusion reactions, contributing to increase comorbidities of the disease. Important measures to prevent these complications in patients are the use of previously phenotyped red blood cells, in addition to the phenotyping of red blood cells from the acceptor patient, determining the correct phenotypic profile and enabling the choice of red blood cells with corresponding antigens to the patient to be transfused. Extensive prophylactic red blood cell genotyping to select donors for patients receiving repeated transfusions over a long period of time is a compelling application of DNA-based blood typing. This is particularly relevant for patients with sickle cell disease where the rate of alloimmunization is high.

[Difficulties of the care of public antigen alloimmunization]. / Difficultés de la prise en charge de l'allo-immunisation anti-public.

Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss.

A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report.

INTRODUCTION: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. CASE PRESENTATION: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000 mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. CONCLUSIONS: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team.

Transfusion practices for patients with sickle cell disease at major academic medical centers participating in the Atlanta Sickle Cell Consortium.

The Atlanta Sickle Cell Consortium represents more than 2600 pediatric and adult patients with sickle cell disease (SCD) in the metropolitan Atlanta, Georgia, area receiving care at four major locations, each providing comprehensive care 24 hours a day, 7 days a week. Both transfusion services that support these sites use two levels of prospective phenotype matching to decrease the rates of alloimmunization. Although exact rates are unknown and are currently under investigation, alloimmunization occurs infrequently with the exception of chronically transfused SCD patients, who represent the minority of active SCD patients. With increasing availability, red blood cell genotyping will be used in the near future both for determination of predicted patient phenotypes and for provision of genotypically matched donor units.

Hemolytic disease of the newborn caused by anti-Wright (anti-Wra): case report and review of literature.

Antibodies to red cell antigens that are found at low frequency in the general population are rare causes of hemolytic disease of the newborn. To understand how to detect these cases, we provide a basic review of routine antenatal maternal antibody testing and report a case of a neonate with severe HDN caused by anti-Wright (anti-Wra), successfully managed with transfusion, phototherapy, and high-dose intravenous immunoglobulin. When hemolysis in a newborn is suspected in the absence of major blood group incompatibility or commonly detected maternal red cell antibodies, a direct antiglobulin test should be performed. A positive DAT should alert the clinician to the presence of maternal antibodies against low-incidence antigens. Antibodies to the Wra antigen are one such rare cause of HDN.

Hemolytic disease of the newborn associated with anti-Jra alloimmunization in a twin pregnancy: the first case report in Korea.

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.

Hemolytic Disease of the Newborn Associated with Anti-Jr(a) Alloimmunization in a Twin Pregnancy: The First Case Report in Korea / 대한진단검사의학회지

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.

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.

Haemolytic disease of the newborn because of rare anti-Vel.

Routine screening for maternal immunization in a 36-year-old woman revealed an alloimmunization against the high-incidence Vel antigen during a second pregnancy. Because of the development of immunoglobulin G-type anti-Vel, the infant developed haemolytic disease of the newborn, with severe jaundice and reticulocytosis. Phototherapy was needed to reduce hyperbilirubinaemia.

Severe hemolytic disease of the newborn due to anti-Di b treated with phototherapy and intravenous immunoglobulin.

The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.

[Foetomaternal erythrocyte incompatibilities: from immunohaematologic surveillance of pregnant women to haemolytic disease of the newborn]. / Incompatibilités foetomaternelles érythrocytaires (IFME): de la surveillance immunohématologique des femmes enceintes à la maladie hémolytique du nouveau-né (MHNN).

Despite the generalization of prevention measures against foetomaternal alloimmunization with anti-D immunoprophylaxis since 1970s, retrospectively 30 years later, its complications (new-born child's severe haemolytic disease, foetal death by anemia or nuclear icterus by bilirubin encephalopathy) have not disappeared. At the same time, alloimmunizations against antigens other than D increase with no possible prevention. As part of the set up in France of regional files analysing and making an inventory of serious foetomaternal incompatibilities requiring in utero or neonatal transfusion, we felt the need to synthesize current data, biological profiles (early screening of erythrocytic alloimmunization and its follow up during pregnancy, father's immunohaematologic status, evaluation of in utero immune haemolysis and impact of new non invasive techniques of diagnosis-RH1 foetal genotypage from ADN foetal of RH1--mothers' maternal plasma), clinical and paraclinical data (evaluation of foetal haemolysis by echography, recording of foetal movements and foetal cardiac rhythm), therapeutic indicators (in utero foetal transfusions or exsanguinotransfusions, neo and postnatal transfusions or exsanguinotransfusions, induced premature labour, newborn's intensive continue phototherapy and Rhesus immunoprophylaxis) in order to enable medical and paramedical professionals to carry out the specific supervision of pregnancies with foetomaternal incompatibility, the in utero, neo- and postnatal treatment of child and the efficient therapeutic prevention of anti-D alloimmunization, in a cooperative way.

Prevalence and specificity of clinically significant red cell alloantibodies in Chinese women during pregnancy--a review of cases from 1997 to 2001.

Guidelines for the prevention and management of red cell alloantibodies during pregnancy, related to anti-D in particular, are well established in Caucasian populations. However, because of the racial difference of the blood group distribution, applicability to Chinese is unknown as a result of insufficient data on the prevalence and their outcome. In a retrospective review of 28,303 (21,327 Chinese) antenatal attendances from 1997 to 2001, 213 (0.79%) women were found to have a total of 230 irregular antibodies. About 137 (0.64%) were ethnic Chinese, and a total of 160 irregular antibodies were identified in their blood samples. About 58 of these Chinese women (0.27%) were found to have 66 clinically significant antibodies. There was only one case of anti-D detected in an Rh(D)-negative subject. Our study shows the overall prevalence of clinically significant antibodies in Chinese women, which was not different from that of the Western population. However, the specificities of the antibodies differ with the commonest antibodies encountered; these being anti-Mi (57.6%), anti-E (19.7%), anti-S (10.6%) and anti-c (7.6%). Neonatal jaundice was observed in 37 babies and 10 of them required phototherapy. The findings support the previous recommendation that routine antenatal antibody screening for Chinese women may not be worthwhile except in Rh(D)-negative subjects or those with an antecedent history of haemolytic disease of the newborn (HDN). The relative high incidence of anti-Mi in the present study and the local population, in general, may warrant a large-scale prospective study of pregnancy outcome in these subjects, especially in the light of the previous case reports of HDN because of anti-Mi.

[The incidence of irregular antibodies in pregnancy: a prospective study in the region of the 's-Hertogenbosch]. / Het vóórkomen van irregulaire antistoffen in de zwangerschap; een prospectief onderzoek in de regio 's-Hertogenbosch.

OBJECTIVE: To determine the incidence and clinical relevance of irregular erythrocyte antibodies (IEA), in multiparous women and in primigravidal with a history of blood transfusion. DESIGN: Prospective longitudinal cohort study. METHODS: In the 's-Hertogenbosch area, the Netherlands, both primigravidae with a previous blood transfusion and multiparous women were tested for IEA in addition to the regular blood tests during the first trimester of pregnancy. If IEA were discovered, the partners were tested for the presence of the antigen involved. Blood samples of children of positive fathers were tested immediately post partum for signs of haemolytic disease of the newborn (HDN). RESULTS: During a 2.5-year period (August 1995-January 1998) a total of 2392 pregnant women were screened for IEA: 2204 multiparous women and 188 primigravidae women. In 65 women 81 IEA were discovered. In the group of 30 children positive for the antigen involved, 12 (40%) had clinical symptoms of HDN; intrauterine death was diagnosed once, one child died immediately after delivery. One child had signs of hydrops fetalis and two children needed an exchange transfusion. Phototherapy and/or regular blood transfusion were given to 7 children. Most cases of HDN were caused by anti-D, anti-Kell and anti-c antibodies. CONCLUSION: Non-RhD-IEA were found in 1.6% of pregnant women screened. First-trimester screening for IEA is recommended as it can be of help in early diagnosis and treatment of HDN.

Consequences for fetus and neonate of maternal red cell allo-immunisation.

AIMS: To study the distribution of clinically important red cell antibodies in pregnancy, and the associated fetal and neonatal morbidity and mortality. METHODS: The case notes of women with clinically important red cell antibodies identified in their serum during pregnancy were reviewed. RESULTS: During a 12 month period 22,264 women were referred for antenatal screening. Clinically important red cell antibodies were detected in 244 (1%). Of these, 100 were anti-D and 144 were non-RhD antibodies. There were three intrauterine deaths, three fetuses required intrauterine transfusion, 10 neonates were transfused, 27 others had phototherapy, and 27 with a positive direct antiglobulin test received no treatment. Early fetal losses occurred in the presence of both high and low levels of anti-D. CONCLUSIONS: Anti-D remains the most common clinically important antibody in pregnancy, and accounts for the greatest fetal and neonatal morbidity and mortality. Of the other antibodies detected, anti-c was associated with most neonatal morbidity. The production of many of the non-D antibodies detected could be avoided by the use of selected red cells when transfusing pre-menopausal women.

[Immunohematologic study and transfusion approach to patients with public antibodies]. / Estudio inmunohematológico y actitud transfusional en pacientes con anticuerpos públicos.

OBJECTIVES: To analyze the different immunohematologic studies required to identify anti-red cell antibodies directed against high incidence antigens and comment the best tranfusion management. PATIENTS AND METHODS: Five patients with suspected anti-red cell alloantibodies directed against high frequency antigens are reported. After a positive antibody screening test (AST), an agglutination test with a commercial panel of 24 red cells was performed. Red cells were treated with proteolytic enzymes and AET to try to identify the circulating antibody. However, it was necessary to send the samples to reference laboratories for definitive identification. In order to evaluate the haemolytic potential of the antibody serum samples were treated with DTT and immunoglobulin subtype was studied with the capillary agglutination test. Finally, we analyze the half life of Cr51 labelled red cells. To obtain compatible blood for transfusion, autologous transfusion and cross-match with blood from direct relatives were performed. RESULTS: AST was positive in every case. A decrease in the agglutination test was observed after ficin treatment in two patients, and an increase in the remaining. The treatment of red cells with ZZAP and AET resulted in a decrease of agglutination in three cases and an increase in the remaining two. Specificity of the antibodies was as follows: anti-Cellano (two cases), anti-Ku (one case) and anti-Yta (two cases). Anti-Kell antibodies were IgG1 and anti-Cartwright antibodies were IgG4. One patient was transfused with autologous blood alone, another patient received compatible blood from direct relatives. A third patient was transfused both with autologous and allogeneic compatible blood. The fourth patient did not need red cell transfusion and, finally the last patient had to be transfused with incompatible blood but no postransfusion haemolysis was observed. CONCLUSIONS: In patients with anti-red cell antibodies against high-frequency antigens, red blood cells treatment with proteolytic enzymes (ZZAP, ficin) and AET are useful techniques to approach to their identification. Beside this, the study of type and subtype of Ig are necessary to know the haemolytic activity of the antibody. Regarding the transfusional management, autologous transfusion, crossmatch with blood from direct relatives and cryopreservation of compatible blood are the most adequate attitudes to cover future needs.