Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies.

A 65-year-old, previously healthy man developed acute renal failure, severe thrombocytopenia and hepatic icterus after a small dose of mefenamic acid (Parkemed). Drug-dependent antibodies reacting against platelets could be identified as the most probable cause for this acute and rapidly reversible disorder. A concomitant hemolytic reaction was not observed and accordingly no drug-dependent red cell antibodies could be demonstrated. The drug-specific antibodies were found only during the acute phase using the platelet immunofluorescence test and a solid-phase immunoassay but not with the monoclonal antibody specific immobilization of platelet antigens assay. After discontinuation of the drug the patient steadily improved and fully recovered until day 22 after admission and drug removal. The clinical course strongly suggests that drug-dependent antibodies against mefenamic acid and/or its metabolites reacting by immune complex mechanism were responsible not only for the thrombocytopenia but also for the renal and hepatic failure.

Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency).

A 38-year-old Russian woman (KZ) has been identified as the fourth proposita with the Inab blood group phenotype. Like the first two propositi, she has a chronic intestinal disorder and, as shown for the third proposita, her Inab phenotype is demonstrably inherited. KZ's serum contained anti-IFC, which reacted with a red blood cell (RBC) membrane component with an Mr of 70,000, which is decay accelerating factor (DAF). Her RBCs lacked all Cromer-related blood group antigens and DAF. Her RBCs were no more susceptible than normal control RBCs to lysis in acid lysis or in rabbit or human antibody-initiated complement lysis tests. Northern blots of total RNA isolated from KZ's Epstein-Barr virus-transformed lymphoblasts showed a marked reduction of DAF mRNA when compared with normal. Polymerase chain reaction (PCR) amplification of cDNA confirmed this reduced level of DAF mRNA. Sequencing of the PCR product showed a 44-nucleotide deletion in the mRNA close to the short consensus repeats IIIa/IIIb intron/exon boundary. This deletion results in a change in the reading frame that places a termination codon six amino acids after the deletion. The putative translation product would lack a glycosyl phosphatidyl-inositol linkage site and, therefore, would not be membrane-bound in the RBC.

Elucidation of apparent non-maternity with DNA probes detecting highly polymorphic single locus systems.

During paternity testing, we encountered the following constellation in the Jk system: the mother's phenotype was Jk(a-b+), while the son was typed as Jk(a+b-). The deduced genotype of the mother would have been Jkb Jkb, and each offspring should then express the Jk(b) antigen. Consequently, non-maternity would be deduced. Since no material was available for extended family studies or HLA typing, except for the DNA of the propositi, only RFLP analysis could bring clarification in this case. The application of four highly polymorphic single locus probes proved the maternity and hence the existence of a Jk-Null allele. We conclude that direct testing at the DNA level may help resolving cases where, by conventional parentage testing, conclusive results are unachievable because of putative 'Null' alleles.

[Usefulness and cogency of gene probes in paternity questions (Personal experiences: 1989/90]. / Brauchbarkeit und Beweisert von Gen-Sonden in Abstammungsfragen (Eigene Erfahrungen: 1989/90).

In cases of disputed parentage usually more than 20 polymorphic systems (red and white cell antigens, serum markers and enzyme markers) have to be analyzed using a battery of different techniques. A more recent method involving analysis of restriction fragment length polymorphism in highly polymorphic genes allows assignment of offspring to their parents. To test the latter method, 28 paternity cases were studied in parallel using conventional systems and detection of RFLPs of probes MS 1, MS 31, MS 43, and g 3, developed by Jeffreys et al. Furthermore, the cogency of exclusion of parentage, the average power of exclusion and the probability of parentage is calculated using published mutation rates and gene frequencies of the four probes. In conclusion, use of the four gene probes has both theoretically and practically turned out to be a powerful method for parentage testing.

[Hemolyzing antibodies to markers of the P blood factor system as a problem in blood transfusion and pregnancy. With reference to serology, biochemistry and genetics]. / Hämolysierende Antikörper gegen Merkmale des Blutfaktorensystems P als Problem für Transfusion und Graviditt. Unter Berücksichtigung von Serologie, Biochemie und Genetik.

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.

[Hemolytic graft versus host reaction cause by immune "auto"-anti A1 formation in an A1 recipient following transplantation of an O kidney. With a review of studies up to now from the literature]. / Uber eine hämolytische Graft-versus-Host-Reaktion durch Immun-"Auto"-Anti A1-Bildung im A1-Empfänger nach Transplantation einer O-Niere. Mit einer Ubersicht bisheriger Beobachtungen aus dem Schrifttum.

The serological data are given of a patient with acquired haemolytic anaemia due to "auto"-antibodies of Anti A1 specificity induced by a group O kidney graft in an A1 recipient as a Graft-versus-Host (GvH) reaction. The gamma-globulin markers Gm (a,x,f) were tested for differentiation between auto- or alloantibody character of the patients "Auto"-Anti A1. The possibility of in vivo neutralization of the Immune-Anti A1 by blood group substance A in the plasma of the patient could not be proven, though initially presumed. The disadvantages of using ABO compatible, but not identical organ donors is pointed out, firstly the possibility of giving rise to ABO induced GvH reactions and, secondly, the reduced chance of group O recipients on the waiting list getting group O graft. A search of the literature revealed 46 similar cases, which are reviewed and their characteristics are discussed.

Analysis of the linkage JK-IGK, MNS-GC and of two other possible linkage groups.

The possible linkage groups JK-JGK, MNS-GC, GPT-ESD and GPT-HP have been analysed in families of middle-European origin. Linkage of JK-JGK and MNS-GC could be confirmed, the group GPT-ESD needs further data and for GPT-HP no evidence of linkage was revealed.

[HLA-DR as a criterion in the selection of organ recipients]. / HLA-DR als Kriterium bei der Auswahl von Organempfängern.

HLA-identity or -compatibility between recipient and donor in cases of organ transplantation results in an improvement of graft survival. Taking into account 10 HLA-DR antigens, the chance to get DR-identical or -compatible recipient/donor pairs is calculated. The total number of HLA-DR identity is approximately 3% and of compatibility approximately 8%. The ABO blood groups are included into these considerations. The expected figures of ABO identity and of ABO compatibility in recipient/donor pairs are combined in some examples with the figures of the HLA-DR system. In cases of already known HLA-DR type and ABO group of the potential recipient, the chance to find an identical or compatible donor is equal the frequency of the patients particular HLA-DR type and ABO group in the population.

No association between GLO I and Hp in the Austrian population.

In contrast to the data published by Payne and Huntsman in 1982, no association between GLO I and Hp phenotypes could be found in a sample of 973 unrelated Austrians.

[Immunohematologic studies on the correlations between (+)-cyanidanol-3-(catergen) therapy and hemolytic anemia]. / Immunhämatologische Untersuchungen über Zusammenhänge zwischen (+)-Cyanidanol-3-(Catergen)-Therapie und hämolytischer Anämie.

The serological findings of three patients suffering from liver cirrhosis and hepatitis accompanied by immunohemolytic anemia (IHA) are described. As a cause of the observed hemolyses the administration of (+)-Cyanidanol-3 (Catergen) was supposed. In contrast to three cases reported in literature antibodies against Catergen were not detectable, therefore a causal connexion between the development of IHA and Catergen could not be proved.

[The forensic significance of the "silent" gene Su (observation of Su in three generations) (author's transl)]. / Die forensische Bedeutung des "stummen" Gens Su (Beobachtung von Su in 3 Generationen).

The complexity of the M-N-S-s system is described, especially the rare silent allele, Su. In a paternity case Su was found in three generations of the family of the accused man, on carrying out comparative dosage investigations. Thus, an exclusion of the putative father, based on an isolated exclusion in the S-s system (SS/ss) could be reversed. The value of plausibility of paternity (19 systems) was 99.985% with the verbal predicate: paternity " practically proven".

[Gc- Tf-subtypes in Vienna and their usefulness in paternity testing (author's transl)]. / Group-specific-component-(Gc-) und Transferrin-(Tf-)Subtypen in der Wiener Bevölkerung und ihre Anwendbarkeit in Paternitätsfällen.

The polymorphisms of the serum proteins Gc and Tf including subtypes are described, their frequencies in the area of Vienna are calculated and their use in paternity cases is discussed.

[Practical and theoretical considerations in blood group serology of red cells (author's transl)]. / Blutgruppenserologie in Praxis und Theorie. Erythrozytäre Merkmale.

Between 1949 and 1979 approximately 1.2 million blood samples were examined and the observed immune antibodies as well as natural occurring irregular antibodies were analysed. The difference of the antigenic strength of red cell markers was determined and the significance of automatic blood grouping discussed. A significant decrease of anti-D antibodies underlines the success of the anti-D-IgG-prophylaxis. Clerical errors and serological failures in a 30 year period of investigations are shown. Recommendations to avoid errors are presented.

[Serologic data from 537 patients with a positive direct Coombs' test (Vienna 1949 to 1979)]. / Serologische Daten von 537 Patienten mit positivem direktem Coombs-Test (Wien 1949 bis 1979).

In the period from 1949--1979 537 patients with positive direct Coombs-reaction were observed, their serological findings are presented and analysed regarding correlations to ABO, Rh, age and sex. Close connexions between the strength of the direct Coombs-reaction, autoantibodies in the serum and the absence of haptoglobin were found as it was expected. The sensitivity of different methods to detect autoantibodies, frequencies and specificities are discussed. Two causes of autoimmune hemolytic anemia with monospecific autoantibodies and four healthy blood donors with unexpected and inexplicable positive direct Coombs-reaction are described.

A further case of chimeric twins: genetic markers of the blood.

A further case of blood chimerism in male twins concerning red and white cells is described. The erythrocyte chimerism could be detected by 5 out of 16 genetic marker systems and the lymphocyte chimerism by the analysis of autosomal polymorphisms of peripheral blood lymphocytes.

Polymorphism of glyoxalase I in Vienna.

Phenotype and gene frequencies of the GLO I polymorphism in Vienna are given. No exception to the postulated rule of inheritance could be found in 23 families with 51 children and 132 mother-child pairs. Linkage with the HLA system is confirmed, but no linkage disequilibrium between GLO alleles and HLA-A, B, C genes was detected. The use of the GLO I polymorphism in paternity cases is discussed.