ABSTRACT
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.
Subject(s)
Erythroblastosis, Fetal/etiology , Isoantibodies/immunology , Adult , Blood Group Antigens/immunology , Erythroblastosis, Fetal/immunology , Female , Humans , Hyperbilirubinemia/therapy , Immunoglobulin G , Infant, Newborn , Phototherapy , PregnancySubject(s)
Anemia, Hemolytic, Autoimmune/etiology , Autoantibodies/immunology , Autoantigens/immunology , Kidd Blood-Group System/immunology , Lupus Erythematosus, Systemic/blood , Adult , Anemia, Hemolytic, Autoimmune/immunology , Antibody Specificity , Autoantibodies/blood , Autoantigens/genetics , Biopsy , Blood Transfusion , Coombs Test , Emergencies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidd Blood-Group System/genetics , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Pneumonia, Mycoplasma/complications , Prednisone/therapeutic use , Skin/pathologyABSTRACT
An 84-year-old women had repeated gastrointestinal bleeding from a Dieulafoy lesion, i.e. a gastric or duodenal ulcer containing an aberrant artery. Her blood group was AB-D negative; her Rhesus phenotype was CCdee. In addition, antibody screening revealed anti-c alloantibodies as the result of a previous transfusion. Donors negative for D and c are very rare in Caucasian populations. Compatible red cell concentrates are available only from the European Bank of Frozen Blood of the Council of Europe, located at Sanquin in Amsterdam, Tthe Netherlands. The patient could be saved by requesting compatible erythrocyte concentrate from this blood bank. Severe blood loss poses a serious challenge in patients who are positive for alloantibodies against blood group antigens with a high frequency in the population, and in patients who are themselves negative for such antigens. The presence of alloantibodies is often the result of previous blood transfusions. In view of the large number of antigens on erythrocytes, one should therefore be conservative as to blood transfusion in order to prevent alloantibody formation.
Subject(s)
Erythrocyte Transfusion/adverse effects , Erythrocytes/immunology , Isoantibodies/biosynthesis , Rh-Hr Blood-Group System , Aged, 80 and over , Blood Banks , Blood Group Incompatibility/etiology , Blood Grouping and Crossmatching , Female , Gastrointestinal Hemorrhage/blood , Gastrointestinal Hemorrhage/therapy , Humans , Phenotype , Time FactorsABSTRACT
A 45-year-old woman underwent a Caesarean section at a gestational age of over 32 weeks. Screening for irregular erythrocyte antibodies in the transfusion laboratory yielded a positive result. It appeared that the patient had for several years been known to have antibodies against At(a), a high-frequency antigen that may cause severe transfusion reactions when incompatible packed cells are administered. No autologous donated blood was available and the only compatible At(a)-negative unit of packed cells in the Blood Bank of the Council of Europe was damaged during the thawing process. A cell saver was therefore used during the Caesarean section, and family members were summoned for donation. This case report illustrates the necessity of a transfusion plan for pregnant women with (rare) irregular antibodies.
Subject(s)
Erythrocyte Transfusion , Erythrocytes/immunology , Isoantibodies/biosynthesis , Blood Donors , Blood Group Incompatibility , Blood Grouping and Crossmatching , Cesarean Section , Female , Humans , Middle Aged , Pregnancy , Pregnancy Complications, Hematologic , Pregnancy OutcomeSubject(s)
Erythroblastosis, Fetal/prevention & control , Pregnancy Complications/therapy , Prenatal Care/statistics & numerical data , Rh Isoimmunization/therapy , Rho(D) Immune Globulin/therapeutic use , Drug Utilization/statistics & numerical data , Europe , Female , Humans , Infant, Newborn , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Pregnancy , Pregnancy Complications/immunology , United StatesABSTRACT
Sixty-four IgG Rh monoclonal antibodies (Mabs) submitted to the Fourth International Workshop on Monoclonal Antibodies Against Human Red Blood Cells and Related Antigens were characterised and tested in quantitative functional assays at five laboratories. The biological assays measured the ability of anti-D to mediate phagocytosis or extracellular lysis of RBC by IgG Fc receptor (Fc gamma R)-bearing effector cells. Interactions of RBC pre-sensitised with anti-D (EA-IgG) with monocytes in chemiluminescence (CL) assays were found proportional to the amount of IgG anti-D on the RBC. Using antibodies to inhibit Fc gamma RI, Fc gamma RII or Fc gamma RIII, the only receptor utilised in the monocyte CL and ADCC assays for interactions with EA-IgG1 was found to be Fc gamma RI. In these assays, enhanced interactions were promoted by EA-IgG3 and additional Fc gamma receptors may have contributed. IgG2 anti-D was not reactive in these assays and EA-IgG4 promoted weak reactions through Fc gamma RI. A macrophage ADCC assay showed that haemolysis of EA-IgG3 was greater than that of EA-IgG1, mediated mainly through Fc gamma RIII. In ADCC assays using lymphocytes (NK cells) as effector cells and papainised RBC target cells, only a minority of IgG1 anti-D Mabs were shown to be able to mediate haemolysis in the presence of monomeric IgG (AB serum or IVIg). These interactions were mediated solely through Fc gamma RIII. Haemolysis via Fc gamma RIII may depend on the presence of certain sugars on the oligosaccharide moiety of IgG. Most Mabs (IgG1, IgG2, IgG3 and IgG4) elicited intermediate, low or no haemolysis in these assays. Blocking studies indicated that low activity IgG1 and IgG4 anti-D utilised only Fc gamma RI. Other IgG1 and IgG3 Mabs appeared to promote haemolysis through Fc gamma RI and Fc gamma RIII while IgG2 was inhibited by Mabs to both Fc gamma RII and Fc gamma RIII, suggesting a variety of Fc gamma R are utilised for anti-D of low haemolytic activity. Excellent agreement between the results of the lymphocyte ADCC assays and antibody quantitation was observed between the participating laboratories.
Subject(s)
Antibodies, Monoclonal/immunology , Immunoglobulin G/immunology , Isoantibodies/immunology , Receptors, IgG/immunology , Antibodies, Monoclonal/chemistry , Antibody-Dependent Cell Cytotoxicity , Glycosylation , Hemolysis , Humans , Immunoglobulin G/chemistry , Immunoglobulins, Intravenous/immunology , Isoantibodies/chemistry , Killer Cells, Natural/immunology , Luminescent Measurements , Lymphocytes/immunology , Macrophages/immunology , Monocytes/immunology , Oligosaccharides/immunology , Phagocytosis , Protein Processing, Post-Translational , Protein Structure, Tertiary , Receptors, IgG/classification , Rho(D) Immune GlobulinSubject(s)
Antigens, Surface/classification , Blood Group Antigens/classification , Erythrocyte Membrane/immunology , Isoantigens/blood , Rh-Hr Blood-Group System/chemistry , Terminology as Topic , Amino Acid Substitution , Antigens, Surface/genetics , Blood Group Antigens/genetics , Carbohydrates/blood , Carbohydrates/immunology , Epitopes/classification , Humans , Rh-Hr Blood-Group System/immunologyABSTRACT
A 66-year-old male patient with severe intravascular hemolysis is presented. Laboratory investigation revealed initially a negative direct antiglobulin test (DAT), suggesting a Coombs-negative hemolytic anemia. Additional testing with monospecific anti-IgA was strongly positive. IgA autoantibodies with anti-e specificity and nonspecific IgA autoantibodies were identified. A diagnosis of IgA-only-associated warm AIHA was made. Treatment included transfusion of multiple e-negative typed red cell concentrates and administration of high-dose prednisone. The pathophysiologic mechanism of the rare IgA-induced warm AIHA is discussed.
Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Antibodies, Anti-Idiotypic/physiology , Autoantibodies/physiology , Hemolysis , Immunoglobulin A/immunology , Aged , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , Antibodies, Anti-Idiotypic/analysis , Autoantibodies/analysis , Coombs Test , Humans , MaleABSTRACT
OBJECTIVE: The aim of this study was to evaluate the clinical value of an antibody-dependent cell-mediated cytotoxicity assay relative to the indirect antiglobulin test titer in the management of Rh D-alloimmunized pregnancies. STUDY DESIGN: Data from 172 Rh D-alloimmunized pregnancies were analyzed retrospectively. The accuracies of the highest antibody titer and of the highest antibody-dependent cell-mediated cytotoxicity assay result during pregnancy to predict fetal and neonatal Rh disease, defined as the need for intrauterine (n = 30) or neonatal (n = 37) blood transfusion, respectively, were assessed. RESULTS: At different cutoff levels with equal sensitivities the antibody-dependent cell-mediated cytotoxicity assay consistently showed a higher specificity than the antibody titer for the prediction of fetal disease. No difference was found between the receiver operating characteristic curves of the 2 tests for the prediction of neonatal disease. CONCLUSIONS: Selection of patients for referral and invasive testing for Rh D alloimmunization may be improved with the use of an antibody-dependent cell-mediated cytotoxicity assay.
Subject(s)
Antibody-Dependent Cell Cytotoxicity/immunology , Rh Isoimmunization/immunology , Coombs Test , Cytotoxicity Tests, Immunologic/methods , Female , Fetal Blood , Hematocrit , Humans , Infant, Newborn , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , ROC Curve , Retrospective Studies , Rh Isoimmunization/blood , Rh Isoimmunization/diagnosis , Rh-Hr Blood-Group System/blood , Rh-Hr Blood-Group System/immunology , Rho(D) Immune Globulin/immunology , Statistics, NonparametricSubject(s)
Anemia, Hemolytic, Autoimmune/immunology , Erythrocytes/immunology , Isoantibodies/blood , Anemia, Hemolytic, Autoimmune/blood , Anemia, Hemolytic, Autoimmune/therapy , Antibody Specificity , Autoantibodies/adverse effects , Autoantibodies/blood , Autoantibodies/immunology , Data Collection , Erythrocyte Transfusion , Erythrocytes/pathology , Hot Temperature , Humans , Isoantibodies/adverse effects , Isoantibodies/immunology , Isoantigens/immunology , Macrophages/immunology , Monocytes/immunologyABSTRACT
Rhesus (Rh) and Kell blood group immunisations are the most frequent causes of haemolytic disease of the newborn. Recently, the molecular bases of the Rh and Kell antigens have been elucidated. Subsequently, specific polymerase chain reactions (PCRs) could be developed to determine the RhD, RhC/Rhc and RhE/Rhe genotypes as well as the KI genotype (from the Kell blood group) with genomic DNA. The tests were applied to genomically determine the foetal Rh and Kell blood groups with DNA obtained from amniotic fluid cells. The genotypes obtained were compared with the Rh phenotypes established by cord blood red cell serology. The PCRs to determine the RhD, Rhc, RhE and Rhe and KI genotypes were found to be reliable. The test for RhC however, resulted in false-positive C genotypes. Indeed, more than half of the subsequently tested C-negative Negroid donors were false-positive with the DNA test. Thus, except for RhC, it is possible to reliably determine the Rh and KI genotypes of a foetus with DNA isolated from amniotic fluid cells. Amniocentesis, however, carries a risk for the pregnancy and therefore the tests will only be justified in pregnant women in whom an antibody has been detected and the father of the foetus is heterozygous for the specific antigen. Recently foetal RhD genotypes were determined in foetal DNA circulating in the plasma of RhD-negative pregnant women. This could eventually lead to the introduction of assays with which the foetal blood group can be determined without any risk to the foetus.
Subject(s)
Blood Group Incompatibility/diagnosis , Fetal Diseases/diagnosis , Kell Blood-Group System/genetics , Polymerase Chain Reaction , Pregnancy Complications, Hematologic/diagnosis , Rh-Hr Blood-Group System/genetics , Adult , Amniotic Fluid/cytology , False Positive Reactions , Female , Fetal Blood/cytology , Fetal Diseases/blood , Genotype , Humans , Isoantigens/blood , Isoantigens/genetics , Pregnancy , Pregnancy Complications, Hematologic/bloodABSTRACT
In two female newborn babies severe haemolytic disease of the newborn developed due to anti-RhD antibodies of the mother. In both cases the results of the last antibody-dependent cellular cytotoxicity (ADCC) test had been < 10% (two and three weeks before parturition respectively) making haemolytic disease unlikely. The ADCC test is used to determine the destructive power of the responsible maternal antibodies. It is believed that with a low ADCC value (< 10%), there is no danger of clinically relevant haemolytic disease. The first neonate recovered after exchange transfusion, the second died notwithstanding extensive supportive therapy. A recent low ADCC value makes serious haemolytic disease unlikely, but does not completely exclude it, as the titre of the causative antibodies can rise very quickly.
Subject(s)
Antibody-Dependent Cell Cytotoxicity , Blood Group Incompatibility/diagnosis , Erythroblastosis, Fetal/immunology , Erythroblastosis, Fetal/prevention & control , Rh-Hr Blood-Group System/immunology , Adult , Blood Group Incompatibility/immunology , False Negative Reactions , Fatal Outcome , Female , Humans , Infant, Newborn , Predictive Value of Tests , Pregnancy , Reference Values , Severity of Illness IndexABSTRACT
An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.
Subject(s)
Coombs Test/methods , Indicators and Reagents/standards , International Cooperation , Humans , Reference StandardsSubject(s)
Blood Group Antigens/immunology , Erythrocyte Membrane/immunology , Isoantigens/blood , Terminology as Topic , ABO Blood-Group System/immunology , Glycoproteins/immunology , Humans , Kell Blood-Group System/immunology , Lewis Blood Group Antigens/immunology , MNSs Blood-Group System/immunology , Phenotype , Rh-Hr Blood-Group System/immunology , Serologic Tests , SwedenABSTRACT
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.