Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta3”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources
PubMed1997

Human monoclonal Fab fragments recovered from a combinatorial library bind specifically to the platelet HPA-1a alloantigen on glycoprotein IIb-IIIa.

BACKGROUND AND OBJECTIVES: Certain clinical conditions are related to the presence of platelet-specific alloantibodies in the patient's serum. We studied the molecular diversity of HPA-1a antibodies to analyze some peculiarities of this antibody response. MATERIALS AND METHODS: Human antibody Fab fragments that bind to the platelet alloantigen HPA-1a on glycoprotein IIb-IIIa (GPIIbIIIa) were generated by using a recombinant phage display system. We established an immunoglobulin G1, kappa combinatorial library from the peripheral blood lymphocytes of a person undergoing a severe posttransfusion purpura. RESULTS: Characterization of Fab clones selected from the fifth round of antigen-specific panning of this library demonstrates a highly specific reactivity to the HPA-1a alloantigen. The nucleotide sequence analysis of representative HPA-la-specific clones reveals at least 3 distinct V1 and 3VH gene segments that present an extensive degree of mutation as demonstrated by comparison of gene usage and homologies to the nearest germline genes. CONCLUSIONS: These human HPA-la-specific Fab reagents should allow us to better understand the molecular mechanism involved in HPA-la alloimmunization.

Amino Acid Sequence↗
PubMed2002

Neonatal alloimmune thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAIT) can occur when a mother is immunized against fetal platelet antigens inherited from the father. Early diagnosis and appropriate platelet transfusion therapy are essential to prevent life-threatening intracranial hemorrhage in the thrombocytopenic fetus or neonate. Five major human platelet antigen (HPA) systems are capable of causing this disorder with HPA-1a indicated most frequently. This article reviews the pathophysiology, clinical aspects, and management of NAIT. We also present our experience with treatment of neonates affected with this disorder.

Antigens, Human Platelet↗
PubMedDate not supplied

Frequency of PLA1 in blacks.

Racial frequencies of platelet-specific antigens in racial groups other than whites have not been studied. The prevalence of PLA1 was determined in white and black blood donors. Two hundred forty-two of 243 blacks were PLA1-positive (99.6%), compared with 242 of 250 whites (96.8%) (p = 0.021). This black population has the highest frequency of PLA1 yet reported.

Antigens, Human Platelet↗
PubMedDate not supplied

First example of familial posttransfusion purpura in two PlA1-negative sisters.

Posttransfusion purpura (PTP) (platelet count 5000/microliter) was diagnosed in a female patient (never transfused, gravida IV, para IV) 1 week after transfusion for hysterectomy in 1978. She did not respond to pooled random-donor platelets but recovered following a single plasma exchange. Her platelets were PlA1 negative, and her plasma contained potent anti-PlA1. In 1986, her sister (never transfused, gravida III, para III) developed PTP (platelet counts 5-15,000/microliter) following surgery-associated transfusion. She did not respond to pooled random-donor platelets. Platelet-associated IgG was markedly elevated (5365) molecules/platelet; normal, less than 660); her plasma contained a potent platelet antibody with anti-PlA1 specificity. Her platelets were subsequently shown to be PlA1 negative. The platelet count did not rise above 30,000 per microliter, despite 3 days of high-dose methylprednisolone sodium succinate and 2 weeks of prednisone (80 mg/day). Later, her platelet count increased and remained normal after steroids were discontinued. The two sisters proved to be HLA-identical, and each possessed one haplotype carrying the DR3 marker, which has been implicated as a risk factor in neonatal alloimmune thrombocytopenia associated with anti-PlA1.

Antigens, Human Platelet↗
PubMedDate not supplied

Platelet transfusion refractoriness associated with two rare platelet-specific alloantibodies (anti-Baka and anti-PlA2) and multiple HLA antibodies.

A 65-year-old patient with pancytopenia resulting from osteomyelosclerosis became refractory to platelet transfusions during long-time transfusion support. He developed two rare, platelet-specific antibodies (anti-PlA2 and -Baka) disguised by strong, multispecific HLA antibodies. The specificity of the platelet-specific antibodies was detected by a newly designed enzyme-linked immunosorbent assay using glycoprotein-specific monoclonal antibodies for immobilization of platelet antigens.

Aged↗
PubMed1989

Testing of maternal sera in pregnancies at risk for neonatal alloimmune thrombocytopenia.

The utility of prenatal testing of maternal serum for platelet-reactive antibody was assessed in 25 women at risk of delivering infants with neonatal alloimmune thrombocytopenia (NAT). Seventeen women were incompatible with their husbands for the PlA1 antigen and three for Baka; in five families, no demonstrable platelet-specific antigen incompatibility was found. Analysis of the clinical outcome demonstrated that women with platelet-specific antibody detectable in any of the assays at any time during gestation were at risk of delivering thrombocytopenic infants (neonatal platelet count 31,250/microliters if mother did have antibody, as compared with 138,750/microliters if she did not; p less than 0.005). When only PlA1-incompatible pregnancies were examined, this association remained significant (mean neonatal platelet count in infants exposed to anti-PlA1, 34,285/microliters; that in infants not so exposed, 243,000/microliters; p less than 0.001). Changes in antibody strength throughout pregnancy did not correlate with the severity of NAT. The combination of the antigen-capture enzyme-linked immunosorbent assay and the indirect immunofluorescence test appeared to be most sensitive in detecting relevant platelet-specific alloantibodies. It is concluded that the detection of platelet-specific alloantibody in maternal serum in pregnancies at risk for NAT predicts moderate to severe NAT. However, the failure to detect such antibody does not always predict a normal neonatal platelet count.

Antigens, Human Platelet↗
PubMed1989

Frequency of platelet-specific antigens among Koreans determined by a simplified immunofluorescence test.

The frequencies of platelet-specific antigens among Oriental populations have not been well studied. This article reports the determination of the frequency of five major platelet-specific antigens among Korean blood donors. Both the PlA1 (Zwa) and Yukb antigens were positive in all of the 126 Koreans tested. Baka and Yuka antigens were positive in 110 (87.3%) and 2 (1.6%) of the 126 subjects, respectively. Ten (11.5%) of 87 Koreans had PlA2 (Zwb) antigens. A simplified immunofluorescence test, the adhesion slide immunofluorescence test, was devised for platelet antigen typing.

Antigens, Human Platelet↗
PubMed1990

Posttransfusion purpura: the therapeutic value of PlA1-negative platelets.

A case of PlA1-associated posttransfusion purpura (PTP) is reported, in which a previously sensitized patient developed life-threatening thrombocytopenia, purpura, hematuria, and bronchial bleeding. The patient was transfused with PlA1-negative single-donor apheresis platelets (from four different donors) on four occasions. The first transfusion resulted in a 1-hour posttransfusion increment of 57 x 10(9) per L. The use of two additional PlA1-negative apheresis platelets provided support for a tracheostomy. Bronchial bleeding leading to respiratory arrest was controlled with a fourth transfusion. All PlA1-negative platelet transfusions resulted in transient increases in the patient's platelet count. This is the first reported case of repeated, transiently effective transfusion of PlA1-negative platelets demonstrated during the acute phase of thrombocytopenia.

Antigens, Human Platelet↗
PubMed1990

Alloimmunization to platelet-specific antigens on glycoproteins IIb-IIIa and Ib/IX in multiply transfused thrombocytopenic patients.

The rate of alloimmunization to platelet-specific antigens associated with platelet glycoproteins (GPs) IIb-IIIa and Ib/IX was studied in 293 multiply transfused thrombocytopenic patients. Antibodies to platelet-specific antigens were measured with a solid-phase assay using platelet GP IIb-IIIa or Ib/IX as the antigenic targets. Nine patients were found to have antibodies to platelet GP IIb-IIIa, and no patients had antibodies to platelet GP Ib/IX. In six of these nine patients, the specificity of the antibody was shown by using GP IIb-IIIa from donors with different platelet-specific antigen phenotypes. In the remaining three patients with antibodies to platelet GP IIb-IIIa, no specificity could be identified. These patients had autoimmune thrombocytopenia in association with lymphoma. The alloimmunization rate to platelet-specific antigens associated with GP IIb-IIIa was 2 percent, whereas the rate of alloimmunization to HLA antigens was 23 percent. Of the patients alloimmunized to HLA antigens, 9 percent also had antibodies to platelet-specific antigens. A poor response to HLA-identical platelet transfusions was observed only in those patients with positive assays in the solid-phase test. These results suggest that the incidence of antibodies to platelet-specific antigens carried on GP IIb-IIIa is low. Platelet-specific antibodies may be found more frequently in patients alloimmunized to HLA antigens than in those not so alloimmunized.

Antigens, Human Platelet↗
PubMed1991

The detection of platelet alloantibodies by flow cytometry.

A flow cytometric procedure was investigated for its ability to detect antibodies directed against blood group A, HLA, and PlA1 (HPA-1a) antigens. When type O sera were tested against platelets from blood group A donors, only 9 of 14 positive reactions were observed. Furthermore, the expression of blood group A varied more than 100-fold on platelets derived from individual donors. When anti-HLA-A2 and -B7 were evaluated, 11 of 11 individuals with HLA-A2 and -B7 antigens reacted. In contrast, when platelets from donors whose HLA antigens included HLA-B8 or -B12 were tested with anti-HLA-B8 or -HLA-B12, respectively, positive reactions were observed in only 3 of 7 instances, despite the fact that the lymphocytes reacted strongly. Platelets from 10 HLA-A2-positive donors, which had been stored for up to 20 months at -70 degrees C, were studied. In all cases, frozen-stored platelets reacted well with an anti-HLA-A2. Limited testing with an anti-PlA1 (anti-HPA-1a) showed equal reactivity with fresh and frozen platelets. Finally, the method was compared to a visual immunofluorescence assay using sera from patients who were refractory to platelet transfusions. The results agreed in 30 of 37 comparisons, and most discrepancies were resolved in favor of flow cytometry. It is concluded that flow cytometry is useful for detecting platelet alloantibodies and possibly for prospective platelet crossmatching, as HLA- and platelet-specific antibodies can be identified by using platelets stored frozen for several months.

ABO Blood-Group System↗
PubMed1991

Captopril-enhanced binding of PlA1 (HPA-1a) antibodies in posttransfusion purpura.

A case of posttransfusion purpura is reported in a 90-year-old patient whose PlA1 antibody (anti-HPA-1a) was found to bind better to HPA-1a in the presence of captopril, a drug the patient had taken. Initially, IgG antibodies were found in the serum that reacted with normal platelets, but the binding of the antibody was increased in vitro by captopril, which suggested that captopril was responsible for the thrombocytopenia. However, in vitro studies demonstrated that the patient's platelets were negative for HPA-1a and that anti-HPA-1a was present in the serum, both of which findings were consistent with the diagnosis of posttransfusion purpura. The binding of this antibody was enhanced 50 percent by captopril in vitro, and increased binding in the presence of captopril did not occur when the anti-HPA-1a was removed. Similar results were obtained with serum containing anti-HPA-1a from another patient with posttransfusion purpura. Thus, captopril may increase the binding of anti-HPA-1a and confuse the determination of the cause of acute thrombocytopenia.

Aged↗