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H Kroll

Publications and source records attributed to H Kroll.

At least 37 records · Page 2Linked to original sources
PubMed1998

Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids--more questions than answers. European Working Group on FMAIT.

The optimal antenatal therapy for fetal thrombocytopenia has not been determined. We analysed 37 cases managed by maternal therapy and observed a successful outcome of maternal treatment in 26% of IvIgG cases and in 10% of steroid-treated cases. The significance of a plateau of the fetal platelet counts during pregnancy, 41% of IvIgG cases and 20%, of cases treated with steroids, is uncertain. It may indicate a stabilization of thrombocytopenia, hence a beneficial effect of therapy, or the natural course of the platelet count in a low-risk pregnancy. Overall outcome was unpredictable, but amongst the therapy failures there were proportionally more severely affected siblings. Further multicentre studies are necessary to establish the optimal antenatal management of high-risk pregnancies.

Adrenal Cortex Hormones↗
PubMed1998

Clinical aspects and typing of platelet alloantigens.

Platelet alloantigens can induce the formation of corresponding alloantibodies when exposed to phenotypically negative individuals. These antibodies are responsible for fetal and neonatal alloimmune thrombocytopenia, posttransfusion purpura, passive alloimmune thrombocytopenia and transplantation-associated thrombocytopenia and may contribute to platelet transfusion refractoriness together with HLA antibodies. Besides antibody detection laboratory diagnosis of the clinical syndromes requires alloantigen typing. Furthermore, typed platelet donors are a prerequisite for effective platelet transfusion therapy. Different techniques for phenotyping are well established and easy to perform but they rely on the availability of antisera. Since the molecular genetic background of the clinically most relevant alloantigens has been elucidated during the last years various genotyping methods have been applied to the platelet membrane polymorphisms and thus facilitated widespread platelet alloantigen typing. Generation of antibodies from phage display libraries and of lymphoblastoid cell lines from donors with all genetic variants will allow further developments.

Adult↗
PubMed1997

[Intrauterine transfusion in fetal alloimmunothrombocytopenia: comparison of maternal and fetal weight-adjusted IgG therapy with exclusive fetal thrombocyte transfusion].

Fetal alloimmune thrombocytopenia is caused by maternal immunization against a fetal platelet antigen and transplacental transfer of the antibody into the fetal circulation. Since 10-20% of the fetuses or newborns are threatened by intracranial hemorrhages, early management is required. Fetal blood sampling should be started between the 20th and 22nd week of gestation to assess fetal phenotype and platelet count. Different concepts to elevate the fetal platelet count have been discussed: maternal intravenous immunoglobulins, fetal intravenous immunoglobulins, or only repeated fetal platelet transfusions. Our investigations suggested that platelet transfusions in short intervals appear to be the only effective regimen to increase platelet counts in thrombocytopenic fetuses at risk.

Birth Weight↗
PubMed1996

Therapy with intravenous immunoglobulin G (ivIgG) during pregnancy for fetal alloimmune (HPA-1a(Zwa)) thrombocytopenic purpura.

We have evaluated the effect of maternal intravenous immunoglobulin G (ivIgG) treatment on platelet counts in fetal alloimmune thrombocytopenia. Seven patients were studied. All of them were multiparous women who had been immunized against the HPA-1a antigen during previous pregnancies and had given birth to at least one severely thrombocytopenic infant. In this study, umbilical blood collection was performed first at the 20th week of gestation and repeated 2-13 times (mean 6 times), depending on the degree of fetal thrombocytopenia. Fetal platelet counting was combined with intrauterine transfusion of 20-30 ml of HPA-1a-negative platelet concentrates to prevent bleeding following umbilical cord puncture. Initial fetal platelet counts ranged from 10,000 to 91,000 per microliters. Maternal treatment with ivIgG (1 g per kg body weight; mean dose 70 g) was given once a week over 7 weeks. In five of seven cases, the basal platelet count did not rise and in two of these cases, it decreased during maternal ivIgG treatment. In one fetus, the baseline platelet count increased from 10,000 to 35,000 per microliters during ivIgG, and in another fetus from 23,000 to 64,000 per microliters. Our observations suggest that ivIgG has no definite benefit for fetal alloimmune thrombocytopenia. Since platelet counts can be very low, careful fetal monitoring by umbilical blood sampling is required. Frequent platelet transfusions in short intervals may be necessary to increase platelet counts in extremely thrombocytopenic fetuses.

Antigens, Human Platelet↗
PubMed1996

Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia.

Autoimmune thrombocytopenic purpura (AITP) is most frequently induced by platelet-specific autoantibodies against epitopes on platelet GP Ib/IX or GP IIb/IIIa. These antibodies are reliably detected on the patients' autologous platelets. So far, studies on the characterization of platelet autoantibodies have been restricted to IgG antibodies. We used the monoclonal antibody immobilization of platelet antigens assay (MAIPA) in a modified version to detect GP-specific IgG, IgM, and IgA antibodies. Platelets of 46.2% of patients carried elevated amounts of IgG antibodies. IgM and IgA antibodies were observed less frequently and showed only weak OD signals in the MAIPA assay. Circulating IgG antibodies in serum were found in 11.5% of patients. Circulating IgM autoantibodies were observed in 8.9% and IgA antibodies in no patient with AITP. Results of direct MAIPA assay were compared with the reactivity of eluates in the platelet adhesion immunofluorescence assay and were found to be highly concordant. Patients with AITP in remission carried high percentages of anti-GP IIb/IIIa. Findings made in this study suggest that autoantibodies of the IgM and IgA classes play only a minor role in the pathogenesis of AITP.

Autoantibodies↗
PubMed1996

Diclofenac-induced immune haemolytic anaemia: simultaneous occurrence of red blood cell autoantibodies and drug-dependent antibodies.

During the last 5 years we have identified a total of 17 patients (nine females and eight males aged between 53 and 85 years) with immune haemolytic anaemia related to diclofenac (a nonsteroidal anti-inflammatory drug). All patients developed acute intravascular haemolysis. Two patients died, and eight patients developed temporary renal failure that required haemodialysis. The direct antiglobulin test was positive with anti-IgG and anti-C3d in all cases, with anti-IgA in 4/10 cases tested, and negative with anti-IgM. The indirect antiglobulin test was moderately or weakly positive in 11 cases, and IgG autoantibodies could be eluted from the red blood cells (RBCs) of all patients. Initially, the diagnosis of autoimmune haemolytic anaemia of warm type was suggested in all cases. All patients had simultaneously developed autoantibodies and drug-dependent antibodies. The majority of drug-dependent antibodies (n = 13) reacted with urine containing the drug and its metabolites (ex vivo antigen), the native drug, and diclofenac-treated RBCs. The antibodies in the remaining four cases were detectable only in the presence of ex vivo antigen. Diclofenac appears to bind only weakly to RBCs in the absence of the drug-dependent antibodies. We conclude that diclofenac forms neoantigens with RBCs that may stimulate the production of autoantibodies and drug-dependent antibodies. The resulting haemolytic syndrome is very similar to autoimmune haemolytic anaemia of warm type.

Aged↗
PubMed1996

[Prenatal management of fetuses with alloimmune thrombocytopenia].

Fetal alloimmune thrombocytopenia is caused by maternal immunization against a fetal platelet alloantigen and transplacental transfer of the antibody into the fetal circulation. Since 10-20% of the fetuses or newborns are threatened by intracranial hemorrhages (ICH) early management is required. Intensive prenatal monitoring should be performed if a maternal HPA-1a antibody is known and a previous infant suffered from thrombocytopenia and/or ICH. Fetal blood sampling (FBS) should be started at 20th to 22nd weeks of gestation to assess fetal phenotype and platelet count. Different concepts to elevate the fetal platelet count have been discussed: corticosteroids, maternal intravenous immunoglobulins (ivIgG), fetal ivIgG and repeated fetal platelet transfusions. In a European survey with data from five centres maternal corticoid treatment and ivIgG infusion were accompanied by increasing fetal platelet counts in only 20 and 24% of the cases, respectively. In fetuses with very low platelet counts only transfusions of compatible platelets in short intervals are able to sustain a safe platelet count. Fetuses with mild thrombocytopenia should be monitored by subsequent FBS since it could be shown that platelet counts tend to decline during gestation. To avoid bleeding complications during and after FBS which was observed in about 5% of the cases every cord vessel puncture should be covered by a platelet transfusion. As no safe and non-invasive therapy exists for fetal alloimmune thrombocytopenia the value of prenatal screening programs in unaffected pregnancies is questionable.

Adrenal Cortex Hormones↗
PubMed1996

[Fetal weight-adjusted intrauterine IgG therapy in neonatal alloimmune thrombocytopenia].

Fetal alloimmune thrombocytopenia is caused by materno-fetal 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), platelet transfusions or fetal IgG transfusions is still controversial. In this study we have evaluated the effect of intrauterine IgG and intraumbilical platelet transfusions on fetal platelet counts. 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 20th week of gestation. Fetal treatment of IgG was given, on av erage, over 9 weeks. In all cases, fetal IgG levels rose significantly whereas platelet counts did not increase following fetal IgG treatment. We conclude that fetal IgG infusions have no detectable effect on fetal allo-immune thrombocytopenia. Since platelet counts can be very low as early as 20 weeks of gestation, careful fetal monitoring by umbilical blood sampling is essential. Platelet transfusions in short intervals appear to be the only effective regimen to increase platelet counts in thrombocytopenic fetuses at risk.

Adult↗
PubMed1995

Genomic RFLP typing of human platelet alloantigens Zw(PlA), Ko, Bak and Br (HPA-1, 2, 3, 5).

The diallelic human platelet alloantigen systems 1-5 have been found to result from single base pair substitutions in the encoding genes of platelet membrane glycoproteins IIIa, Ib, IIb and Ia. This is the basis of DNA methods for determination of platelet alloantigens. In this study, 98 blood donors were typed in the HPA-1, 2, 3 systems and, for the first time, in the HPA-5 system. Serologically obtained data (MAIPA and platelet agglutination) were compared with results from analysis of restriction fragment length polymorphisms (RFLP). Discordances were found in the HPA-2 and 3 systems and can be ascribed to false typing results in both the serological and genomic methods. In the HPA-1, 2 and 5 systems, all samples were typed correctly with RFLP analysis. Serologically, two donors were falsely typed positive with anti-HPA-2b in platelet agglutination and one donor with anti-HPA-3a in MAIPA assay. In the HPA-3 system, another four donors were misinterpreted to be HPA-3a negative in RFLP analysis. Possible technical problems in PCR-RFLP-typing are discussed and another strategy of HPA-1 typing using the restriction enzyme Scr FI is evaluated.

Antigens, Human Platelet↗
PubMed1995

Alloimmunization against Iy, a low-frequency antigen on platelet glycoprotein Ib/IX as a cause of severe neonatal alloimmune thrombocytopenic purpura.

Neonatal alloimmune thrombocytopenia (NAIT) is usually induced by platelet-specific antibodies against HPA-1a (Zwa) or HPA-5b (Bra). Recently, low-frequency alloantigens on the platelet glycoprotein (GP) IIb/IIIa complex have been discovered as a cause for NAIT. In this report, a new low-frequency platelet-specific alloantigen, Iy, is described which induced severe NAIT. The corresponding antigen was detected in 1/249 unrelated German blood donors. Antibody binding assays with trypsin-digested platelets (ELISA, immunoprecipitation with biotin-labelled platelets) indicate that the antigen is not localized on the glycocalicin moiety of GP Ib alpha, but may be situated on the remnant moiety of GP Ib alpha, GP IX or GPIb beta. Apparently, Iy is not related to the HPA-2 (Ko) antigen system.

Adult↗
PubMed1994

A point mutation leads to an unpaired cysteine residue and a molecular weight polymorphism of a functional platelet beta 3 integrin subunit. The Sra alloantigen system of GPIIIa.

Recently, we described a low frequency platelet alloantigen on human platelet membrane glycoprotein (GP) IIIa, termed Sra, that was involved in neonatal alloimmune thrombocytopenia. To identify the molecular nature of the Sra alloantigen, we analyzed the nucleotide sequence of polymerase chain reaction-amplified GPIIIa mRNA, and found a C2004-->T substitution in seven Sra positive individuals which results in an Arg636-->Cys polymorphism within the cysteine-rich region of GPIIIa. Analysis of allele-specific recombinant forms of GPIIIa that differed only at amino acid residue 636 showed that anti-Sra alloantibodies reacted with the Cys636, but not the Arg636, recombinant form of GPIIIa. Interestingly, under reducing conditions, the Cys636 form of GPIIIa migrated with a slightly increased apparent molecular weight compared with the Arg636 form. Following treatment with Endoglycosidase H, both allelic forms of GPIIIa exhibited the same mobility, however the Sra epitope was lost. Sra positive platelets express the same number of GPIIb-IIIa complexes on their surface as wild-type Sra negative platelets, and also aggregate normally in response to a variety of platelet agonists. Based upon these results, we conclude that 1) GPIIIa residue 636 specifically controls the formation and expression of the Sra alloantigenic determinant, and 2) an unpaired cysteine residue alters the N-linked glycosylation pattern of the extracellular domain of GPIIIa, but affects neither the degree of surface expression nor the adhesive function of the GPIIb-IIIa complex.

Amino Acid Sequence↗
PubMed1994

Maternal intravenous immunoglobulin treatment does not prevent intracranial haemorrhage in fetal alloimmune thrombocytopenia.

In fetal alloimmune thrombocytopenia (FAIT) the fetus is threatened by intracranial haemorrhage (ICH); therefore early diagnostic and therapeutic intervention is required. We followed the clinical course of a 30-year-old woman during her fifth pregnancy after she had given birth to a child with alloimmune thrombocytopenia due to anti-Zwa. The fetus was monitored by 13 fetal blood samplings (FBS) always followed by transfusion of either maternal or compatible donor platelets. Intravenous immunoglobulin (ivIg) treatment of the mother was begun at 20 weeks of gestation when the fetal platelet count was 36 x 10(9)/l. The fetal platelets were typed Zwa positive by DNA analysis. Despite 11 weeks of maternal ivIg treatment fetal platelet counts progressively declined to 6 x 10(9)/l and ICH occurred. Subsequently, the fetus was successfully managed by intrauterine platelet transfusions at shorter intervals (3-5 days) and elective Cesarean section was carried out at 35 weeks of gestation. We conclude that maternal ivIg treatment does not prevent ICH in FAIT. The treatment of choice for severely affected cases is serial FBS combined with transfusion of compatible platelets.

Antigens, Human Platelet↗
PubMed1994

[Comparison of serologic typing and DNA typing of platelet alloantigens].

Platelet alloantigens of the Zw, Ko, Bak und Br systems were determined by restriction fragment length polymorphism (RFLP) analysis of appropriate PCR products in 98 unselected patients. Results were compared with serological typing by monoclonal antibody immobilization of platelet antigens (MAIPA) and platelet agglutination.

Agglutination Tests↗
PubMed1994

[A single base substitution is responsible for the origin of "private" platelet Sra antigens affects molecular weight polymorphism of glycoproteins IIIa].

Some of the genetic polymorphisms of the platelet membrane glycoproteins (GP) IIIa are known to be responsible for alloantibody formation (Zw, Yuk). These antibodies may be involved in neonatal alloimmune thrombocytopenia, posttransfusion purpura, and sometimes in the state of refractoriness to platelet transfusion. Recently we described the first 'private' alloantigen on platelets residing on the 66-kDa membrane-bound fragment of GP IIIa. Further molecular genetic studies showed that the Sr polymorphism is associated with a C to T substitution at base 2004 in the GP IIIa gene resulting in an Arg/Cys amino acid dimorphism at position 636. Transfection of COS cells with recombinant forms of GP IIIa cDNA demonstrated that this amino acid dimorphism is responsible for the formation of the Sra epitope. Furthermore, the Sra variant of GP IIIa showed a slightly increased molecular weight which is presumably caused by different glycosylation.

Antigens, Human Platelet↗
PubMed1994

[Two modifications of MAIPA assays for the demonstration of platelet antibodies].

The monoclonal antibody immobilization of platelet antigens assay (MAIPA), published in 1987, is now used by many laboratories for detection of platelet antibodies. False-positive results were observed with sera containing anti-mouse IgG and in cases where MAIPA was employed to characterize platelet-specific antibodies of the IgM class. Modifications of MAIPA which completely eliminate these artifacts are described.

Animals↗
PubMed1994

[Anti Ko(a) as a cause of neonatal alloimmune thrombocytopenia].

Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal immunization against a paternal antigen on fetal platelets. The antigens mostly involved are Zwa (PlA1) and Br(a). The Ko alloantigen system which is localized on the N-terminal region of glycoprotein Ib usually causes antibody formation in polytransfused patients but is only rarely implicated in NAIT. Ko(a) antibodies raised in the mother of a thrombocytopenic newborn were shown to be detectable by platelet agglutination and MAIPA assay if the antigen-bearing N-terminal glycocalicin is protected from proteolytic degradation.

Antigens, Human Platelet↗