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C Mueller-Eckhardt

Publications and source records attributed to C Mueller-Eckhardt.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Immunization against a new, infrequent alloantigen (Iy) on the platelet glycoprotein Ib/IX as a cause of a serious case of neonatal alloimmune thrombocytopenia].

Neonatal alloimmune thrombocytopenia is the consequence of maternal alloimmunization against platelet-specific alloantigens, usually PIA1 or Br(a). The clinical picture is characterized by signs of haemorrhagic diathesis as a result of marked thrombocytopenia. In the last years, rare cases of immunization against 'low-frequency' or 'private' platelet alloantigens on the platelet glycoprotein (GP) complex IIb/IIIa have been found. This is the first report on NAIT due to maternal immunization against a low-frequency platelet alloantigen ('Iy') localized on platelet GP Ib/IX.

Antigens, Human Platelet↗
PubMed1994

[Prenatal substitution therapy in fetal alloimmune thrombocytopenia].

Fetal alloimmune thrombocytopenia is caused by maternofetal transfer of platelet antibodies. Since the thrombocytopenic fetus is threatened by intracranial hemorrhage, prenatal observation and, if necessary, treatment is required. However, the benefit of therapeutic options, including intravenous IgG (ivIgG) or platelet transfusions, is still controversial. In this study we have evaluated the effect of maternal ivIgG and intraumbilical platelet transfusions on fetal platelet counts in 7 cases. All patients were multiparous women who were immunized against the Zwa antigen during previous pregnancies and had given birth to at least one severely thrombocytopenic infant. First umbilical blood was sampled at the 26th week of gestation. Maternal treatment of ivIgG was given over 7 weeks, the mean number of intrauterine platelet transfusions was 5.9. In 6 of 7 cases the basal platelet count before transfusion did not rise or even further decreased during maternal ivIgG treatment. In one case the baseline platelet count increased from 18,000/microliter to 60,000/microliter during ivIgG. We conclude that, in general, ivIgG alone has no detectable effect on fetal alloimmune thrombocytopenia. Since platelet counts can be very low as early as 20 weeks of gestation, careful fetal monitoring by umbilical blood sampling is required. Platelet transfusions in short intervals appear to be the only effective regimen to increase platelet counts in extremely thrombocytopenic fetuses.

Antigens, Human Platelet↗
PubMed1994

[Transfusion-associated acute pulmonary insufficiency: a rare, but life-threatening transfusion reaction].

Two patients developed within several hours after blood transfusion severe shortness of breath which required temporary artificial ventilation. X-ray pictures of the chest showed pulmonary edema in both patients. No cardiac causes for edema were found. Detection of granulocyte antibodies in the sera of one patient and one blood donor confirmed the suspected diagnosis of transfusion-related acute lung injury.

Acute Disease↗
PubMed1993

Pregnancy complicated by heparin associated thrombocytopenia: management by a prospectively in vitro selected heparinoid (Org 10172).

A pregnant woman treated with unfractionated heparin for pelvic vein thrombosis in the 26th week of her first pregnancy developed heparin-associated thrombocytopenia. Diagnosis was verified by the heparin induced platelet activation (HIPA) assay, which revealed cross reactivity to various LMW heparins, but not to the LMW heparinoid Org 10172. Upon intravenous (i.v.) anticoagulation with the heparinoid Org 10172 the platelet count returned to normal within 6 days and remained stable throughout the entire treatment period. After 3 weeks i.v. treatment with Org 10172, administration was changed to the subcutaneous route. At term a healthy boy was delivered spontaneously. No Org 10172 was detected in the cord blood, while therapeutic levels were measured in the maternal blood. The infant's platelet count was normal, but serum from the cord blood induced platelet activation in the presence of heparin, indicating the transplacental passage of heparin-dependent maternal antibodies.

Adult↗
PubMed1993

Immune thrombocytopenia associated with hemorrhagic diathesis due to ibuprofen administration.

Acute thrombocytopenic purpura temporally related to the oral administration of ibuprofen developed in a patient with ankylosing spondylitis. Clinical manifestations, with sudden onset occurring within 12 h of drug ingestion and rapid increase of platelet counts following discontinuation of the drug, were characteristic of an antibody-mediated immune pathomechanism. Immunological studies demonstrated IgM and IgG antibodies in the patient's serum that were capable of binding to allogenic platelets in the presence of a metabolite preparation. This finding suggested that an ibuprofen metabolite, rather then the drug itself, was the antigenic agent responsible for the immune reaction. Despite its widespread therapeutic use, ibuprofen has not been described previously as causing immune-mediated thrombocytopenia.

Aged↗
PubMed1993

Report on the Fifth International Society of Blood Transfusion Platelet Serology Workshop.

The Fifth International Society of Blood Transfusion (ISBT) Platelet Serology Workshop took place in 1990. A total of 21 laboratories participated in the wet workshop. Results were discussed at a meeting of the International Committee on Standardization in Haematology (ICSH) Expert Panel on Platelet Serology at the Joint Congress of the ISBT and the American Association of Blood Banks in Los Angeles in November 1990. Each of the participants analyzed 37 serum samples for platelet-reactive alloantibodies and isoantibodies. In addition, two drug-dependent (quinine) platelet-specific antibodies had to be identified among a subset of seven sera. For the first time in a platelet serology workshop, five platelet suspensions had to be typed for the alloantigens of the HPA-1, -3, -4, and -5 systems.

Antibodies↗
PubMed1993

Frequency of platelet-specific antigens among Indonesians.

This study reports the frequencies of the alloantigens of four major platelet-specific alloantigen systems among Indonesians. One hundred and sixty-eight unrelated Indonesian blood donors were phenotyped for the alloantigens of the Zw (PIA, HPA-1), Bak (HPA-3), Yuk (Pen, HPA-4), and Br (HPA-5) systems by use of a glycoprotein-specific immunoassay. All were positive for the alloantigens Zwa, Yukb, and Brb. Three (1.79%) and 1 (0.59%) of the 168 donors were positive in testing for Zwb and Yuk(a) antigens, respectively. Fifteen (9.26%) of 162 Indonesians had Br(a) antigens. Of the 166 donors tested, 121 (72.89%) were Bak(a) positive and 134 (80.72%) were Bakb positive. In addition, the phenotype frequency of Nak(a) was determined by using monoclonal antibody OKM5 in a platelet enzyme-linked immunosorbent assay. Its frequency in the present cohort was 95.83 percent (161/168). This study confirms the differences in platelet antigen distributions in Asians and whites. Both glycoprotein IV deficiency and the Yuk polymorphism are also found among Indonesians.

Antigens, Human Platelet↗
PubMed1993

The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis.

In order to determine whether platelets contain specific messenger RNA encoding for HLA class I molecules, polymerase chain reaction (PCR) was performed with RNA from different platelet donors. Two amplified 300 bp and 279 bp cDNA fragments were obtained which encompassed sequences from 321 to 620 and from 795 to 1073. The 300 bp fragment encodes exon 2 and exon 3, the 279 bp encodes a portion of exon 4, exon 5, exon 6 and a portion of exon 7. A 300 bp nested PCR product from one donor, that encoded for the highly polymorphic region alpha 2, was cloned and sequenced. The resulting nucleotide sequences fitted to the expected sequence for HLA B*3801 of this donor. Sequence analysis of the 279 bp PCR product demonstrated the presence of exon 5 encoding for the 117 bp transmembrane domain. In addition, de novo protein biosynthesis was studied by radioimmunoprecipitation of HLA class I molecules from 35S-methionine metabolically labelled platelet lysates with a monoclonal antibody (mab) w6/32 specific for a monomorphic epitope on the heavy chain of HLA class I antigens. Analysis of the immunoprecipitates on SDS polyacrylamide gel electrophoresis showed a specific band with apparent molecular weight (M(r)) of 44 kD corresponding to integral membrane HLA protein. On the basis of these results, we conclude that platelets contain specific messenger RNA encoding for HLA class I molecules and have the capability to synthesize the integral HLA membrane protein.

Base Sequence↗
PubMed1993

Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides.

The interaction of sulphated oligosaccharides (SO) with platelets and the antibody of heparin-associated thrombocytopenia (HAT type II) was investigated. 3H-heparin binding to platelets was inhibited by different SO, depending on their grade of sulphation. Dextran sulphate, pentosan polysulphate, and heparin were more effective than were LMW heparins. De-N-sulphated heparin and a LMW heparinoid (Org 10172) had no effect. Platelets preincubated with high-grade SO and washed, released serotonin in the presence of HAT sera without additional heparin. Platelets preincubated with HAT sera and then washed were not activated when heparin was added. Only high-grade SO which inhibited heparin binding to platelets caused platelet activation with HAT sera. However, low- and high-grade SO in high concentrations (0.11 g/l) inhibited serotonin release induced by HAT sera and heparin. 32P-phosphorylation of platelet proteins was enhanced by HAT-IgG and heparin and by heat-aggregated IgG, and was inhibited by the moab IV.3. High SO concentrations inhibited only the effect of HAT-IgG and not that of aggregated IgG. We assume that the antigen in HAT involves a releasable platelet protein with a binding site for SO. This was corroborated by studies with an anti-platelet factor 4 antibody causing Fc-receptor dependent platelet activation inhibitable by high SO concentrations.

Antigen-Antibody Complex↗
PubMed1993

Analysis of granulocyte-reactive antibodies using an immunoassay based upon monoclonal-antibody-specific immobilization of granulocyte antigens.

To detect human granulocyte-reactive antibodies, a glycoprotein-specific enzyme immunoassay for platelet antibodies was adapted for the use of granulocytes as target cells. Peripheral blood granulocytes were simultaneously incubated with a monoclonal antibody (mAb) and the serum to be investigated. After solubilization, aliquots of the cell lysate were transferred to plastic tubes coated with goat anti-mouse antibodies. Following immobilization of the trimolecular (mAb-glycoprotein-human antibody) complex it was detected by addition of enzyme-labelled goat anti-human antibodies using a luminescence technique. This assay allowed identification of different granulocyte-reactive antibodies present in the same sample without the need for complicated absorption studies. Alloantibodies against HLA and the granulocyte-specific NA antigens as well as isoantibodies against the Fc-gamma-receptor III (FcRIII) were detectable using mAb-specific immobilization of granulocyte antigens (MAIGA). Binding of autoantibodies to the FcRIII and to the CD 11b/CD18 complex could be shown.

Animals↗
PubMed1993

Influence of granulocyte antibodies on granulocyte function.

The following substances were tested for their influence on granulocyte function: 8 sera that contained human granulocyte-specific alloantibodies against the antigens NA1, NA2 and NB1, two HLA antisera, and the monoclonal antibodies W6/32 and CLB-FcR-gran 1. The effects examined included spontaneous and directed migration, immune phagocytosis inhibition and the generation of oxygen radicals. Using the under-agarose technique, spontaneous migration of sensitized granulocytes was normal. For all antibodies tested, the chemotactic index for N-fMLP, LTB4 and opsonized zymosan was greater than 1. Granulocyte immune phagocytosis of sensitized sheep red blood cells was strongly inhibited by all alloantisera and monoclonal antibodies. The generation of oxygen radicals after triggering the respiratory burst with sensitized sheep red blood cells was also strongly inhibited in the chemiluminescence assay. Immune phagocytosis and chemiluminescent response of granulocytes lacking the corresponding antigen of the tested alloantibodies were not affected. Since sensitization of neutrophils with F(ab')2 fragments of the monoclonal antibodies W6/32 and CLB-FcR-gran 1 showed lower inhibition of generation of oxygen radicals after triggering, Fc-dependent interaction with the target cells seems to be necessary for inhibition. Our results suggest that binding of NA1-, NA2- or NB1-specific alloantibodies to granulocytes not only causes neutropenia, but also impairs granulocyte function.

Chemotaxis, Leukocyte↗
PubMed1993

The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).

The human GPIa/IIa complex, also known as integrin alpha 2 beta 1, serves as a major receptor for collagen in platelets and other cell types. In addition to its role in platelet adhesion to extracellular matrix, GPIa/IIa is also known to bear the clinically important Br(a) and Brb alloantigenic determinants, which can result in antibody-mediated platelet destruction. Immunochemical studies showed that the Br antigenic epitopes reside solely on the GP Ia subunit and do not depend on sialic acid residues. To define the polymorphism responsible for the Br alloantigen system platelet RNA PCR technique, was used to amplify GPIa mRNA transcripts. Nucleotide sequence analysis of the amplified platelet GPIa cDNA from Br(a/a) and Brb/b individuals revealed a single A<-->G polymorphism at base 1648. MnlI RFLP analysis of cDNA from serologically determined individuals confirmed that this polymorphism segregates with Br phenotype. This single base change results in a substitution of Lys (AAG) in Br(a) to Glu (GAG) in Brb at amino acid residue 505 In spite of the reversal in charge at this position, however, we found no difference in the ability of Bra and Brb homozygous platelets to adhere to collagens types I, III, or V, nor did anti-Bra or anti-Brb alloantibodies interfere with platelet adhesion to any of these fibrillar collagens. The identification of the nucleotide substitution that defines the Bra/Brb alloantigen system will now permit both pre- and postnatal diagnosis for Br phenotype.

Antigens, Human Platelet↗
PubMed1993

[Detection of drug-induced antibodies to erythrocytes in the gel test].

Drug-induced immune hemolytic anemia is a serious hematological disorder which results from increased red blood cell destruction due to the production of autoantibodies, drug (metabolite)-dependent antibodies (DDAb) or both types of antibodies, even in one patient by the same drug. One of the major problems related to DDAb is that the causative drug (metabolite) usually does not bind tightly to target cells, and the antibodies are completely removed from the cells by conventional washing procedures, i.e. by the antiglobulin test. We have recently shown that the microtube geltest, by which the antiglobulin test is performed without washing the cells, is a highly sensitive and reliable alternative method for the detection of all kinds of DDAb. The results obtained with different DDAb are discussed.

Anemia, Hemolytic, Autoimmune↗
PubMed1993

[Blood donation by relatives in pediatrics].

Directed blood donations from family members are frequently desired for pediatric patients. A reduced risk for transfusion-transmitted diseases could not be proved. There are indications that recommendation of directed blood donation could oblige members of risk groups for HIV or hepatitis infection to donate blood since their voluntariness is not guaranteed and the possibility of self-exclusion is omitted. In some instances it may be necessary to perform directed blood donations from relatives because of immunological or medical principles, e.g. transfusion of maternal platelets in neonatal alloimmune thrombocytopenia. In contrast, directed blood donations should not be realized for most hematologic-oncologic patients because they bear the risk of immunisation against alloantigens of the donor and can thus prevent a later bone marrow transplantation from relatives. Inspite of reservations against directed blood donations for individual cases the pediatrician and the transfusion medicine service will have to decide on blood donations from relatives. In any case the blood products should be irradiated with 30 Gy to avoid a transfusion-related graft-versus-host-reaction.

Adolescent↗