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C Mueller-Eckhardt

Publications and source records attributed to C Mueller-Eckhardt.

At least 109 records · Page 6Linked to original sources

Autoantibodies and drug- or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis.

Two patients with acute immune haemolytic anaemia caused by diclofenac are described. Both patients had developed IgG drug-independent autoantibodies and drug-dependent antibodies. The drug-dependent antibodies in one patient reacted with red blood cells (RBC) only in the presence of urine from patients receiving diclofenac (ex vivo antigen) but not in the presence of the drug itself or its known metabolites. This antibody appeared to recognize a trace metabolite which has not yet been identified. The drug-dependent antibodies in the second patient reacted with RBC in the presence of urine as ex vivo antigen as well as in the presence of the drug itself and its main metabolites. Incorrect diagnosis of such cases often is due to the occurrence of autoantibodies and/or unusual drug metabolism and excretion.

Aged↗

Follow-up study on 24 patients with nomifensine-induced immune haemolytic anaemia.

There is as yet only scarce information regarding the natural history and long-term clinical sequelae of patients who survive the acute complications of severe drug-related immune haemolysis, the effect of the mode of drug administration for sensitization and possible alterations of serological characteristics of drug-dependent antibodies during the postsensitization period. We therefore followed 24 patients with nomifensine-induced haemolytic anaemia for up to 6 years after the haemolytic attack. All patients had suffered from a severe haemolytic episode. None of the patients showed any abnormal findings upon reinvestigation (complete history and physical examination; extended biochemical and haematological laboratory status), particularly with respect to renal function. Drug-dependent antibodies remained detectable in 19 of 21 sera, while drug-independent autoantibodies, demonstrable in six patients during the acute phase of haemolysis, could no longer be detected. With regard to the mode of drug administration, the majority of patients (15 out of 24) had developed the haemolysis at the beginning (immediately after a single dose) or during a second course of drug therapy (n = 8 and 7, respectively). The immune response did not appear to be dose- or time-dependent. This study confirms the benign long-term prognosis of patients who survive life-threatening complications in drug-induced immune haemolytic anaemia. In addition, it indicates that drug-dependent antibodies may remain detectable over long periods of time, and that irregular drug administration might be associated with a higher risk of drug sensitization.

Anemia, Hemolytic↗

High-dose intravenous gammaglobulin for neonatal alloimmune thrombocytopenia in twins.

We report the successful treatment of neonatal alloimmune thrombocytopenia with repeated infusions of high-dose immunoglobulin G (400 mg/kg/d for 5 days) in twins. Platelet counts increased within 3 days from less than 20 x 10(9)/l to more than 70 x 10(9)/l. The first twin survived without neurological or other sequelae. The second twin had probably developed intracranial hemorrhage (ICH) in utero. This infant developed long-term neurological sequelae with blindness, cerebral palsy and infantile spasms. Implications of the therapeutic approach and prevention of severe complications in pregnancies with known risk for neonatal alloimmune thrombocytopenia are discussed.

Autoimmune Diseases↗

[Immunologic aspects of thrombocyte transfusion].

This review surveys immunological aspects of platelet transfusions with regard to definition of refractoriness, clinical factors influencing platelet increments, possibilities to delay or prevent immunization, antibody specificities involved in refractory states, immunological complications of platelet transfusions and associations between production of platelet-specific antibodies (i.e. anti-Zwa and anti-Bra) and HLA class II antigens.

Antibody Specificity↗

[Particle formation in disposable systems for the V.50.1 (Haemonetics) cell separator].

Recently, we described small, free particles in the disposable cell separator platelet apheresis systems for the cell separator V.50.1 (Haemonetics). In the meantime, the production procedure for this system has been modified and a new material (Ceramic-polypropylene) is in use for the rotating seal. We could not find the formerly described particles in 32 of these newly developed systems.

Adult↗

[Preliminary results of the DGTI Workshop for evaluating the reactivity of monoclonal anti-D].

Within a working group of the German transfusion society, a workshop was conducted to evaluate the reactivity of monoclonal anti-D supernatants. During this evaluation 10,000 samples were tested, including 325 Du-samples, with 3-5 IgM type antibodies and 3-4 IgG type antibodies, which were selected to also find 'D-variants'. In general, the reactivity with D+ red blood cells was good, and specific in respect to D negative samples. Some samples have been found to have a different pattern of reactivity than the monoclonal antibodies used. Dependent on the method and on the antibody, in some studies up to 100% of Du samples could be detected by anti-D of the IgM type. Some data indicate that the reaction with Du samples is not dependent on titer. In addition, in separate studies the data show a correlation of reactivity in respect to the Rh-phenotype (CcDuee greater than ccDuEe).

Antibodies, Monoclonal↗

Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia.

A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa-specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a "private" platelet alloantigen that bears significance in rare instances of NAIT.

Adult↗

Preparation of leukocyte-poor platelet concentrates from buffy coats by a new type of quadruple bag.

A new quadruple blood bag system for collection of platelet concentrates is described. The principle modification consists of a smaller (150 ml) buffy coat bag in conjunction with SAG-mannitol for red cell preservation. Platelet yield and function were comparable to conventional techniques, leukocyte contamination was lower (1.7 +/- 1.3 x 10(7) per unit). The system is recommended for specialized institutions with a high demand of blood components.

Blood Platelets↗

Hereditary types of thrombocytopenia with giant platelets and inclusion bodies in the leukocytes.

Three forms of hereditary thrombocytopenia with giant platelets and inclusion bodies in the leukocytes have thus far been recognized. The May-Hegglin anomaly is characterized by giant platelets and spindle-shaped inclusion bodies in the leukocytes, which consist of 7-10 nm parallel-lying filaments. The Fechtner syndrome is a variant of the Alport syndrome, with inclusion bodies consisting of dispersed filaments, ribosomes and a few segments of rough and smooth endoplasmic reticulum. The Sebastian platelet syndrome shows the same platelet and leukocyte morphology observed in the Fechtner syndrome, but the additional anomalies e.g., the Alport syndrome, are lacking. The clinical signs and symptoms are variable. Most patients show only a mild bleeding tendency or are asymptomatic, but cases of severe postoperative hemorrhage have also been reported. Platelets can vary greatly in number, but are usually in the range of 20,000 to 120,000 platelets/microliters, showing a mean platelet volume of 15-20 fl, unimpaired in vitro function and, in addition to their size and unorganized microtubular system, normal morphology. To date, no platelet membrane defects have been defined. Because the megakaryocyte number and platelet kinetics are normal, the pathogenesis of thrombocytopenia in these giant platelet syndromes is unresolved; this is also true of the leukocyte inclusion bodies. Because of the ubiquity of electronic particle counters, asymptomatic patients are increasingly being identified, but they are often misdiagnosed as having autoimmune thrombocytopenia.

Bernard-Soulier Syndrome↗

Failure of the platelet-activating-factor antagonist WEB 2086 BS for treatment of chronic autoimmune thrombocytopenia.

Thirteen patients with chronic autoimmune thrombocytopenia (AITP) were treated for 14 days with daily oral doses of 120 mg of the novel platelet-activating-factor (PAF) antagonist WEB 2086 BS. Clinical bleeding symptoms remained essentially unchanged in 9 patients and became more pronounced in the post-treatment period in 4 patients. In no case was an increase in platelet counts observed. While the PAF antagonist was well tolerated subjectively during treatment, most patients exhibited a prolongation of the sensitive "hemostasis time" (a modified bleeding time test) after treatment, but the Duke bleeding time was not changed. We conclude that the PAF antagonist WEB 2086 BS is ineffective for treatment of chronic AITP and should be used with caution in thrombocytopenic patients.

Adult↗

Incidence and specificity of HLA-DP antibodies in pregnancy sera.

A total of 630 human pregnancy sera were investigated for HLA-DP antibodies (ab) by monoclonal antibody-specific immobilization of leukocyte antigens (MAILA) using monoclonal antibody (mAB) B7/21.2 and selected B-lymphoblastoid cell lines from the Tenth International Histocompatibility Workshop reference panel. DP-specific abs were detected in 86 of 330 sera (26.1%) of a retrospective series selected for positive reactions in lymphocytotoxicity screening, and in 29 of 300 unselected sera (9.7%) of a prospective series. Approximately 80% of DP-reactive sera were also positive in lymphocytotoxicity test for class I and/or class II ab. On the other hand, sera containing lymphocytotoxic ab for both class I and class II ab revealed the highest incidence of DP ab (35%). Out of 115 DP-reactive sera, 28 clearly presented one or more DP specificities. Absorption/elution studies revealed complex patterns of reactivity in some sera which were similar to those of known mABs and possibly reflect supertypic DP specificities and/or serological cross-reactions. Serological DP typing of individuals by the MAILA technique appears promising.

Antibodies, Monoclonal↗

Autoimmune hemolytic anemia associated with an IgA autoanti-Gerbich.

A third patient with autoimmune hemolytic anemia due to autoantibodies against Gerbich antigens is described. The patient's serum contained strong hemagglutinating antibodies of the IgA plus IgG classes which reacted with all red blood cells (RBC) tested, but not with Gerbich-negative cells. Although the patient was typed as Gerbich positive, his serum failed to react with his own RBC, and the sensitization of his erythrocytes with autoantibodies was only demonstrable if eluates of his RBC were used. The failure of the autoantibodies to react with autologous RBC at the peak of hemolysis most likely reflects a weakening of Gerbich antigens during the course of autoimmune hemolytic anemia.

Adult↗

Donath-Landsteiner autoimmune hemolytic anemia in children. A study of 22 cases.

During the last 4 years, we have studied a total of 531 adults and 68 children with clinically and serologically well-defined forms of immune hemolytic anemias. Among these, Donath-Landsteiner (DL) hemolysis was the underlying disease in 22 of the 68 children (32.4%), but was not observed in adults. All children with DL hemolysis suffered from acute infections presumably of viral origin. In none of the cases was the DL hemolysis suspected clinically. Boys were more often affected than girls. The hemolytic episodes were severe, but resolved within few weeks. Serologically, all patients had a strongly positive direct antiglobulin test (DAT) using anti-C3d reagents, but a weak (n = 6) or negative (n = 16) IgG-DAT. DL hemolysins were always weak and transient, detectable with enzyme-treated red blood cells (RBC) in all, with untreated RBC in 12 of 22 sera. To explore the reason why these weak antibodies can cause extensive hemolysis in vivo, we compared the action of DL antibodies and of cold agglutinins (anti-I) on RBC by several reincubations at 4 and at 37 degrees C. The data obtained from this experiment demonstrate a stronger aggravation of hemolysis by DL than by anti-I antibodies, presumably due to low-affinity interaction between the cells and DL antibodies.

Adult↗

[Comparison of 4 crossmatching methods for predicting the success of platelet transfusion].

Long term platelet transfusion support often results in alloimmunization of the recipients and refractoriness to further platelet transfusions. Crossmatch tests between the recipients' serum and the donor platelets offer a potential solution to this problem. In the present study, 207 donor-recipient pairs were studied in 65 patients. We compared four assays (LCT, PAIFT, ELISA and MAIPA) in their ability to predict the response in patients receiving multiple platelet transfusions. All four techniques showed a similar predictability of transfusion outcome (79-80%). Of the four assays, the LCT had the highest specificity (100%) and the PAIFT had the highest sensitivity (70%). In comparison to the three other techniques, the MAIPA assay, a glycoproteinspecific immunoassay, offers the possibility to distinguish between HLA-specific (cytotoxic and noncytotoxic) and platelet-specific antibodies in the same serum specimens. Our results demonstrate that HLA antibodies are the major cause of platelet transfusion refractoriness. Platelet specific (i.e. anti-Zwb) and ABO antibodies are involved in approximately 10%.

Adolescent↗

[Passive immunotherapy with polyvalent immunoglobulins in women with habitual abortions].

Intravenous immunoglobulins (IVIG) were used in an alternative approach to immunotherapy with allogeneic leukocytes to prevent recurrent spontaneous abortions (RSA). Twenty five women with a history of greater than or equal to 3 unexplained RSA were treated with IVIG during their next pregnancy. An initial dose of 30 g (0.5-0.6 g/kg body weight) was administered at gestational week 5-6. Treatment was continued every 3 weeks with 20 g (0.3-0.4 g/kg) and terminated by week 25. In primary RSA the success rate was 82-85%, which is in the same range as for leukocyte therapy. In contrast, IVIG was successful in only 40% of secondary aborters. We conclude that IVIG can be an effective treatment for prevention of primary RSA. Compared to leukocyte therapy the risks of transmission of infections and of HLA immunization can be avoided.

Abortion, Habitual↗