Consequences of nucleic acid amplification testing for blood transfusion centres.
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Biomedical subjects
Publications and source records attributed to C P Engelfriet.
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With a view to terminological uniformity, blood group serologists, immunologists and transfusion physicians should refer only to the "ABo' (zero) in stead of the "ABO' system. They also should use "HLA antibodies' in stead of "anti HLA antibodies'. The new Dutch spelling "resus' in stead of "Rhesus' is incorrect from a historical point of view.
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Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.
In cases of Rh D alloimmunization, strong results in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay (> 80% lysis as compared to that of the standard anti-D serum) are indicative of severe hemolytic disease to occur in the newborn (HDN). However, discrepant cases were found in which the maternal anti-D gave strong ADCC results and the newborns had no or only mild hemolysis. In the majority of these cases the mother had produced monocyte-reactive IgG alloantibodies, mostly with HLA-DR specificity. Such antibodies may be capable of blocking FcR-mediated functions of the fetal MPS, and it has been postulated that they inhibit destruction of anti-D-sensitized red cells. We here describe 2 families in which such discrepancies were noticed. In 1 family, in spite of ADCC results of > 80%, the Rh D-positive second child was born without signs of hemolysis. However, the Rh D-positive third child suffered from very severe hemolytic disease. The mother had produced monocyte-reactive HLA-DR antibodies in the second pregnancy which, however, did not react with the cells of the third child. In the other family, the severely Rh D-alloimmunized mother had lost her fourth child because of intrauterine death due to HDN. The Rh D-positive fifth child was born with only mild HDN and only in this pregnancy had the mother produced such antibodies. These 2 case histories give further evidence that maternal monocyte-reactive alloantibodies, in both these cases directed against HLA-DR antigens, can protect the Rh D-positive child against hemolytic disease in case of severe Rh D alloimmunization.
IgG present in the circulation of newborn infants is predominantly of maternal origin. In cases of severe Rh D alloimmunization, the maternal anti-D anti-bodies may lead to Rh D-haemolytic disease of the newborn. However, an impaired placental transport of maternal IgG could be associated with the protection of the fetus/newborn against haemolytic disease as shown in this case report.
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The extent to which maternal anti-Rh(D) antibodies support lysis of erythrocytes by monocytes in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay is closely correlated with the severity of Rh(D) haemolytic disease of the newborn infant (HDN). However, in some cases HDN is much milder than would be predicted from the ADCC value. We postulated that maternal ADCC-blocking alloantibodies against paternal antigens on monocytes can protect these infants against severe haemolysis. We studied 13 severely Rh(D)-alloimmunised mothers whose infants showed unexpectedly mild HDN (group I) and 14 women with similar ADCC values but whose infants had severe HDN (group II). 7 group-I women had monocyte-reactive IgG alloantibodies that inhibited lysis by paternal monocytes in the ADCC. No such antibodies were found in group II (p less than 0.01). In 6 of the 7 serum samples with monocyte-reactive antibodies, the antibodies had HLA-DR specificity. Our findings suggest that Rh(D)-positive children of some severely Rh(D)-alloimmunised women may be protected from severe HDN by maternal non-HLA-class-I, IgG alloantibodies against paternal monocyte blood-group antigens. These antibodies may inhibit the mononuclear phagocyte system of the fetus.
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We describe 2 patients with thrombocytopenia and autoantibodies in the blood against platelet membrane glycoprotein (GP) IIb/IIIa, in whom reactivity of the antibodies with their antigen was greatly diminished in the presence of sodium EDTA. One patient also showed a marked thrombocytopathy, suggesting a functional blocking of GP IIb/IIIa by these autoantibodies. These observations show that some immunologically important autoantibodies can easily be missed in routine serological investigations in which EDTA blood is used, obscuring the autoimmune nature of a thrombocytopenia and possibly of a thrombopathy as well.
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In 1987 the Central Medical Blood-transfusion Committee of the Netherlands Red Cross decided to modify their definition of 'Rh-negative' as it applied to blood donors. Until then the term Rh-negative had been reserved for donations that grouped as C- and E-negative and failed to react with IgG anti-D by the indirect antiglobulin test (IAT). From June 1987, however, donations were considered to be Rh-negative if they failed to react with two strong anti-D sera. An evaluation is presented over the first one and a half years of working with the new definition, the problems that were encountered and the measures that are taken to guarantee the quality of Rh testing.
The extremely rare phenotypes p, P1k and P2k (0.0005-0.0006%) of the blood group P system are usually found in consanguinous families. In the serum of these persons haemolytic antibodies with the specificity anti-PP1Pk and anti-P are found, causing severe haemolytic reactions after transfusion of incompatible blood. Because of their rarity it is difficult to find compatible blood donors. The antibodies are also associated with abortion early in pregnancy. Since 1948 at the "Institut für Blutgruppenserologie der Universität Wien" 4 persons of the phenotype p and 3 of the type P2k were observed in altogether 5 families. Two of them needed blood transfusions, the one p patient received p blood from her sister, who likewise gave blood to the other p patient. This latter patient additionally received three blood units which had been stored in liquid nitrogen and came from Austria and from the European bank of frozen blood in Amsterdam (Council of Europe). The pedigrees of three families with 5 probands out of the 7 observed cases could be reconstructed and showed consanguinity, partly some generations back. A genetic model valid at the moment for the biosynthetic pathway of the P antigens is demonstrated and the appropriate serological characteristics of the haemolytic antibodies are shown. The seven antibodies are partly IgG and partly IgM antibodies, optimally reacting using the indirect antiglobulin test or enzyme-treated red cells. The range of the antibody titres was between 1:8 and 1:1024. Absorption of Anti-PP1Pk sera with red cells of type P1 to get Anti-Pk and inhibition with hydatidcyst fluid and globoside to receive Anti-P and Anti-P1 + Pk, respectively were partly successful.