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Biomedical subjects

V Kiefel

Publications and source records attributed to V Kiefel.

At least 73 records · Page 4Linked to original sources
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

[Risk of immunization to blood cells and diagnostic and therapeutic implications].

Transfusion of blood and blood components may be fraught with serious immunologically mediated side effects. Acute hemolytic reactions are still the most common cause of fatal transfusion sequelae. The incidence of alloimmunization against erythrocyte antigens as studied in long-term transfused patients with thalassemia depends on the age at the beginning of transfusion therapy. HLA alloimmunization is often associated with refractoriness to platelet transfusions and febrile transfusion reactions. Neonatal alloimmune thrombocytopenia and post-transfusion purpura are elicited by platelet-specific antibodies reacting with determinants on platelet glycoproteins IIb/IIIa, Ib/IX, and Ia/IIa. Another serious complication of transfusion therapy, transfusion-related acute lung injury, is caused by granulocyte-specific alloantigens in donor plasma. Graft-versus-host disease is a rare but dangerous complication of blood transfusion which mainly affects patients with impaired T-cell-related immunity.

Blood Cells↗
PubMed1993

[Post-transfusion purpura: clinical and immunologic studies in 38 patients].

BACKGROUND: Posttransfusion purpura (PTP) is characterized by severe thrombocytopenia and hemorrhagic diathesis about 1 week following blood transfusion. Only few studies exceed the description of single cases. MATERIALS AND METHODS: Clinical data from 38 patients were analyzed. Platelet antibodies were studied by complement binding, immunofluorescence, MAIPA assay and acid elution techniques. RESULTS: All patients were female. The mean age at onset was 60.7 years (35-78 years). 4 patients received whole blood, 28 were transfused with packed RBC. 11 of 13 patients (85%) had febrile, non hemolytic adverse reactions during the transfusion. The interval between transfusion and onset of purpura extended from 2 to 14 days, with a peak at 7 and 8 days. Hemorrhagic symptoms lasted 10.1 days. The minimal platelet count was 7.0 x 10(3)/microliters. The platelet count increased to over 50 x 10(3)/microliters after 13.9 days (n = 26), and to over 100 x 10(3)/microliters after 17.0 days (n = 22). 2 patients died of hemorrhagic complications. 24 patients were treated with glucocorticoids, 20 with intravenous immunoglobulins (ivIG), 17 of these received both therapies. 14 of 19 patients (74%) responded well to ivIG. In contrast, platelet transfusions produced no adequate increment, in 6 cases they provoked febrile reactions. 35 sera (92.1%) contained anti-Zwa, either alone or together with anti-HLA or in 1 case with anti-Bra. Anti-Baka and anti-Bakb were found in 1 case each. In 5 patients, anti-Zwa could be eluted from autologous Zwa-negative platelets. CONCLUSIONS: The broad clinical spectrum of PTP could be shown. Since 5% of the patients succumb to bleeding complications, the application of ivIG as therapy of choice is recommended. The phenomenon of elution of alloantibodies from autologous platelets is interpreted as a consequence of 'pseudo-specificity' which may play a role in the pathogenesis of PTP.

Adult↗
PubMed1993

[Bernard-Soulier syndrome. An important differential diagnosis in chronic thrombocytopenia with bleeding complications].

Hereditary types of thrombocytopenia are often clinically misdiagnosed as chronic autoimmune thrombocytopenia. The Bernard-Soulier syndrome is a recessively inherited thrombocytopenia and -pathy associated with giant platelets. Bleeding time is usually prolonged, hemorrhage can be severe. In a Turkish thrombocytopenic boy autoimmune thrombocytopenia was diagnosed at the age of 11 months because the platelet count raised from 40.000/microliter to 100.000/microliters under treatment with steroids. The correct diagnosis of Bernard-Souiler syndrome was made at the age of 2 1/2 years. His also affected 13 year old sister had been treated for chronic autoimmune thrombocytopenia for years and suffered from severe hypermenorrhoea. Family history revealed consanguinity of the parents. Diagnosis of Bernard-Soulier syndrome was made by crossimmunoelectrophoresis and immunofluorescence showing absence of the glycoprotein complex Ib/IX.

Adolescent↗
PubMed1992

May-Hegglin anomaly: a rare cause of thrombocytopenia.

A family with four and an unrelated family with three individuals affected by the May-Hegglin anomaly are described. Platelet counts were markedly reduced and were correctly determined only in the counting chamber. Bleeding time and platelet aggregation were always normal, but platelet nucleotide concentrations (ATP and ADP) were elevated. The platelet glycoprotein complexes Ib/IX, IIb/IIIa and Ia/IIa were quantitatively normal. Platelet-associated IgG was slightly elevated, although thrombocytopenia was presumably not caused by an immunological mechanism. Morphological investigations showed giant platelets and spindle-shaped inclusion bodies in the granulocytes, while their function (phagocytic capacity, radical production) was normal. To exclude hereditary types of thrombocytopenia, morphological and family investigations are required to avoid misdiagnosis with far-reaching diagnostic and therapeutic consequences.

Blood Platelet Disorders↗
PubMed1992

Leucine33-proline33 substitution in human platelet glycoprotein IIIa determines HLA-DRw52a (Dw24) association of the immune response against HPA-1a (Zwa/PIA1) and HPA-1b (Zwb/PIA2).

Alloantibody formation against HPA-1a (Zwa/PIA1) has, to date, only been found in HLA-DRw52(a+) (Dw24) individuals. Alloimmunization against the product of the other HPA-1 allele, HPA-1b, is rare. We have been able to evaluate ten cases of HPA-1b alloimmunization in Europe in order to study whether there is an association between HLA phenotype and anti-HPA-1b antibody formation. HLA typing of these patients was performed with particular attention to the DRw52a specificity using specific T-cell clones. No association with DRw52a or any other known HLA phenotype was found. This finding implies that the amino acid substitution leucine33-proline33 in GPIIIa, responsible for HPA-1a/b, is of primary importance for the association of anti-HPA-1a antibody formation with DRw52a. These data show that the amino acid polymorphism affects the presentation of the immunogenic oligopeptides of HPA-1a and -1b in the HLA class-II groove.

Antigens, Human Platelet↗
PubMed1992

Heparin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan.

Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin-like substance, Arteparon, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

The MAIPA assay and its applications in immunohaematology.

The monoclonal antibody immobilization of platelet antigens (MAIPA) assay has proved to be a reliable and useful tool in platelet immunology. After immunochemical localization of the most important platelet allo- and autoantigens on platelet glycoproteins (GPs) IIb/IIIa, Ia/IIa, Ib/IX, the corresponding antibodies can easily be detected with this technique because mAbs against these membrane constituents are now readily available. The assay also allows reliable typing of platelet alloantigens. Detection of GP-specific PAIgG (by direct MAIPA) has proved to be a specific diagnostic sign of AITP. The MAIPA assay allowed identification of 'new' alloantibody specificities including alloantibodies against 'low-frequency' antigens. The principle of this technique has successfully been applied to characterize antibodies against lymphocytes, endothelial cells and granulocytes.

Antibodies, Monoclonal↗
PubMed1992

Anti-HPA-4b (anti-Yuk(a)) neonatal alloimmune thrombocytopenia: first report in a Caucasian family.

Neonatal alloimmune thrombocytopenia (NAIT) is caused by platelet antigen incompatibility between the mother and fetus. NAIT is mainly due to alloimmunization; the frequency varying among ethnic groups. In Caucasians HPA-1a is the antigen most frequently implicated. In Japan, NAIT due to anti-HPA-4b antibody has already been described, but this is the first case to be reported in Caucasians.

Adult↗
PubMed1992

Quantitation of soluble HLA class I antigen in human albumin and immunoglobulin preparations for intravenous use by solid-phase immunoassay.

Soluble HLA class I antigens in human plasma preparations possibly play a role in HLA sensitization and modulation of the immune response. We therefore have determined their concentration in albumin and immunoglobulin preparations from several commercial sources and compared these values to the concentration in normal human sera. For this purpose we used a newly developed solid-phase enzyme immunoassay employing rabbit anti-mouse antibody, monomorphic HLA class I monoclonal antibody and a polyclonal enzyme-linked beta 2-microglobulin-specific antiserum. Soluble HLA antigen concentration in 14 albumin batches from 6 manufacturers and in 16 immunoglobulin batches from 11 manufacturers ranged from 0 to 9.6 and from 0 to 20.9 ng/ml. The concentration in normal human sera 1,328 +/- 954 ng/ml (n = 54). We conclude that the concentration of soluble HLA concentration in albumin and immunoglobulin preparations is more than 50 times lower than in normal human serum, but considerable differences exist between products of various manufacturers.

Antibodies, Monoclonal↗
PubMed1992

[Detection of platelet-specific alloantigens in 400 unselected blood donors].

Antibodies against platelet specific alloantigens cause neonatal alloimmune thrombocytopenia, posttransfusion purpura, and they are sometimes found in polytransfused patients. In the last few years, new alloantigens were discovered in addition to the Zw-, Bak-, and Ko-alloantigens. In order to obtain representative data for the frequency of all platelet alloantigens in the European population, we typed 400 blood donors of our institution. No significant differences between our findings and data already published were found for the antigens of the HPA-1, -2, -3, and -5 systems; however, no HPA-4b (Yuka)-positive and no Naka-negative individual was found among the 400 blood donors tested. The Siba and HPA-2b antigens proved to be identical. The 'low-frequency' alloantigen Sra was not identified among the 400 individuals tested.

Antigens, Human Platelet↗
PubMed1992

[Clinical and serologic studies in 34 patients with post-transfusion purpura].

Posttransfusion purpura (PTP) is a rare transfusion reaction characterized by a severe bleeding tendency and thrombocytopenia which occurs approximately 1 week after transfusion of platelet-containing blood components in patients previously immunized against platelet alloantigens. 34 cases of PTP were studied. Our patients were all female with a mean age of 60.8 years (35-78 years, n = 32). The inciting blood components were whole blood (4) or red cell concentrates (28). The interval between transfusion and onset of purpura ranged from 2 to 14 days with a clear maximum at 7 and 8 days. In 11 of 13 patients (85%) transfusion was accompanied by febrile, nonhemolytic transfusion reactions. Hemorrhagic symptoms lasted 9.4 days (3-37 days, n = 16). The mean minimal platelet count was 7.1 x 10(3)/microliters [(0-28) x 10(3)/microliters, n = 29]. The platelet count rose to over 50 x 10(3)/microliters after 13.9 days (2-61 days, n = 26), over 100 x 10(3)/microliters after 17.0 days (3-75 days, n = 22). In 1 patient, PTP led to death due to intracranial hemorrhage. 22 patients were treated with corticosteroids, 20 patients with intravenous immunoglobulins (IVIG), 17 of these patients received both. Therapy with IVIG was successful in 14 of 19 patients, whereas platelet transfusions (n = 18) were not able to evaluate the platelet count. Serological analysis showed that antibodies against the HPA-1a antigen either alone (18), in combination with HLA antibodies (12) or with anti-HPA-5b (1) were responsible in 91.2%, while antibodies against other platelet antigens were rarely implicated. In elution experiments HPA-1a antibodies could be eluted from the autologous HPA-1a-negative platelets. We suppose that these antibodies had a pseudo-specificity and were involved in the destruction of the patients' own platelets.

Adult↗
PubMed1992

[Neonatal isoimmune thrombocytopenia by anti-GP IIb/IIIa].

Neonatal alloimmune thrombocytopenic purpura is caused by maternal platelet-specific alloantibodies which react on fetal platelets with the corresponding antigen. We describe a 30-year-old female patient with type I Glanzmann thrombasthenia who developed an isoantibody against the platelet GP IIb/IIIa complex before or during pregnancy. The platelet count in the male newborn was 35 x 10(9)/l, but there were no signs of cerebral hemorrhage. Following infusion of 2 g/day i.v. IgG on 3 consecutive days, platelet counts rose to normal values. An isoantibody reacting with the GP IIb/IIIa complex of all platelet donors tested was found in the maternal serum using the MAIPA assay. Thus, immune-mediated neonatal thrombocytopenia may be caused by platelet isoantibodies against GP IIb/IIIa as well as by platelet-specific alloantibodies and by maternal autoantibodies.

Adult↗
PubMed1992

[Prevalence of lupus anticoagulant, autoimmune hemolysis, thrombocytopenia and disorders of platelet function in unselected patients with SLE].

Prevalence of lupus anticoagulant (LA) in patients with systemic lupus erythematosus (SLE) and clinical manifestations vary widely between different clinical series. We investigated the relation between LA, autoimmune hemolytic anemia (AIHA), thrombocytopenia and platelet dysfunction in 80 unselected patients with SLE. AIHA was found in 6 patients (7.5%) and thrombocytopenia in 10 patients (12.5%), which was not related to platelet aggregation abnormalities. Compared to controls, patients with SLE showed significantly prolonged aPTT and kaolin clotting time (KCT), but platelet aggregation induced by both collagen and thrombin was not impaired. LA activity as defined by Rosner et al. (index for LA/ICA) was found in 15 patients (18.9%). Only 7 of these patients showed a positive platelet neutralization test (Triplett) and 9a positive tissue thromboplastin inhibition test (Schleider). In our SLE patients 23.7% have suffered from at least one thrombotic complication. In patients with LA activity thromboembolic complications were increased (p < 0.05). Thrombocytopenia was found in 6% of LA-negative but in 20% of LA-positive patients.

Abortion, Spontaneous↗
PubMed1991

A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia.

Heparin-associated thrombocytopenia (HAT) is a severe complication of heparin therapy. Its diagnosis is difficult. Conventional assays employ platelet aggregometry (PAA) and/or 14C-serotonin release (SRA) which are either insensitive (PAA) or require radioactive tracers (SRA). We here describe a newly developed sensitive and rapid assay based on visual evaluation of heparin-induced platelet activation (HIPA) in microtiter wells. Using sera of 34 patients with clinically suspected HAT we found the HIPA assay to be as sensitive as the SRA and superior to PAA. The HIPA assay allows investigation of crossreactivity with different types of heparins, low molecular weight (LMW) heparins and heparinoids. Three patients who required further parenteral anticoagulation and in whom the HIPA assay was negative before treatment with the LMW heparinoid Org 10172, were treated with this new heparinoid without adverse reactions. We conclude that the HIPA assay may be a useful tool for differential diagnosis and therapy in patients with HAT.

Cross Reactions↗
PubMed1991

Blood group A and B determinants are expressed on platelet glycoproteins IIa, IIIa, and Ib.

We report the localization of A, B blood group determinants on intrinsic glycoproteins using anti-A, B IgG antibodies. By radioimmunoprecipitation, anti-A and anti-B precipitated three bands with apparent molecular masses in sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of 159, approximately 120 and 85 kDa under non-reduced conditions and 145, approximately 126 and 97 kDa under reduced conditions. In two-dimensional gel electrophoresis (isoelectric focussing/SDS-PAGE) these three bands could be resolved into six spots and fulfilled previously defined criteria for platelet membrane glycoprotein complexes I a/IIa, Ic/IIa, I b/IX and II b/IIIa. The results were supported by data obtained by an assay employing antibody-specific immobilization of platelet antigens (MAIPA). By this technique, blood group A, B determinants were shown to be immobilized by monoclonal antibodies specific for GPIa, Ic', IX, IIb/IIIa and strongly by mab specific GPIIa, but not by mab specific for HLA class I molecules. The more precise localization on platelet glycoproteins was achieved by immunoblotting technique by which blood group A determinants could be assigned to GPs IIa, IIIa and Ib.

ABO Blood-Group System↗
PubMed1991

HPA-5b (Br(a)) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases.

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia (NAIT). The HPA-1a (PIA1, Zwa) antigen is by far the most common antigen implicated in NAIT. However, today another antigen often linked with that affection is HPA-5b (Br(a)). This is a report of 39 cases of NAIT involving the HPA-5b antigen. Thrombocytopenia may be of grave consequence. Three infants developed intracerebral haemorrhages (ICH). Of these, one died presumably as a consequence of ICH. Central nervous system (CNS) sequelae in the neonatal period was observed in two children. The potential hazards of death or disabling neurologic sequelae following intracerebral haemorrhage call for rapid and reliable diagnosis and effective therapy. Because there is high risk that subsequent pregnancies might be also affected by NAIT, the mothers of a previously affected child should be managed similarly to the HPA-1b mothers (PIA2, Zwb). The antenatal diagnosis of thrombocytopenia should be made and if necessary the in utero therapy instituted.

Antigens, Human Platelet↗