Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Bak<sup>a</sup>) detectable only in whole platelet assays

Harrison, Christopher; Curtis, Brian R.; McFarland, Janice G.; Huff, R. W.; Aster, Richard H.

doi:10.1046/j.1537-2995.2003.00533.x

Cited by 53 publications

(56 citation statements)

References 26 publications

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“…This evaluation demonstrated the equal quality of the commercially available ELISA kits in the detection of platelet‐specific alloantibodies when compared to the in‐house assay of MAIPA. Similar to previous reports , the difficulties in detection and identification of anti‐HPA 3a antibodies were emphasized.…”

Section: Discussionsupporting

confidence: 84%

Platelet Antibody Analysis by Three Different Tests

Sareban

Macher

Drexler

et al. 2014

Clinical Laboratory Analysis

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Section: Discussionsupporting

confidence: 84%

Platelet Antibody Analysis by Three Different Tests

Sareban

Macher

Drexler

et al. 2014

Clinical Laboratory Analysis

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“…11,28 Specificity of antibodies for the GPIIb/IIIa or GPIb/IX complexes was characterized by the modified antigen capture enzyme-linked immunosorbent (MACE) assay. 11,30 In brief, platelets were sensitized by antibody in the presence of 0.4 mM quinine and washed in phosphate-buffered saline (PBS) containing drug. The sensitized platelets were then lysed in Triton X-100 detergent and solubilized GPs were captured in microtiter wells by immobilized mAbs AP3 (anti-GPIIIa), AP2 (anti-GPIIbIIIa), AP1 (anti-GPIb), and 142.11 (anti-GPIb).…”

Section: Detection and Characterization Of Quininedependent Antibodiesmentioning

confidence: 99%

Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies

Bougie

Wilker

Aster

2006

Blood

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Immune thrombocytopenia induced by quinine and many other drugs is caused by antibodies that bind to platelet membrane glycoproteins (GPs) only when the sensitizing drug is present in soluble form. In this disorder, drug promotes antibody binding to its target without linking covalently to either of the reacting macromolecules by a mechanism that has not yet been defined. How drug provides the stimulus for production of such antibodies is also unknown. We studied 7 patients who experienced severe thrombocytopenia after ingestion of quinine. As expected, drug-dependent, platelet-reactive antibodies specific for GPIIb/IIIa or GPIb/IX were identified in each case. Unexpectedly, each of 6 patients with GPIIb/ IIIa-specific antibodies was found to have a second antibody specific for drug alone that was not platelet reactive. Despite recognizing different targets, the 2 types of antibody were identical in requiring quinine or desmethoxy-quinine (cinchonidine) for reactivity and in failing to react with other structural analogues of qui-

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“…Platelets were washed and incubated with 1:10 diluted murine plasma and an FITC-conjugated F(abЈ) 2 goat anti-murine IgG Fc (1:100 diluted) and examined by flow cytometry as previously described. 31 An antibody to the human ␣IIb␤3 complex (AP2) was used as a positive control for human platelets, and an antibody to murine GPIb␣ was used as a positive control for recognition of mouse platelets. Buffer served as a negative control and buffer-diluted plasma from control mice served as an internal negative control.…”

Section: Assay To Detect An Immune Response To ␣Iib␤3mentioning

confidence: 99%

“…The ratio of antibody binding to platelets was determined by dividing the MFI of platelets with mouse (A) plasma by the MFI of platelets with control buffer as previously described. 31 A ratio above 2.0 denotes a positive immune response to platelet proteins. Human platelet studies complied with institutional guidelines approved by the Human Research Review Committee of the Medical College of Wisconsin.…”

Section: Assay To Detect An Immune Response To ␣Iib␤3mentioning

confidence: 99%

Therapeutic expression of the platelet-specific integrin, IIb 3, in a murine model for Glanzmann thrombasthenia

Fang

Hodivala‐Dilke

Johnson

et al. 2005

Blood

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Integrins mediate the adhesion of cells to each other and to the extracellular matrix during development, immunity, metastasis, thrombosis, and wound healing. Molecular defects in either the ␣-or ␤-subunit can disrupt integrin synthesis, assembly, and/or binding to adhesive ligands. This is exemplified by the bleeding disorder, Glanzmann thrombasthenia (GT), where abnormalities of the plateletspecific integrin, ␣IIb␤3, prevent platelet aggregation following vascular injury. We previously used a retrovirus vector containing a cDNA cassette encoding human integrin ␤3 to restore integrin ␣IIb␤3 on the surface of megakaryocytes derived from peripheral blood stem cells of GT patients. In the present study, bone marrow from ␤3-deficient (␤3 ؊/؊ ) mice was transduced with the ITG␤3-cassette to investigate whether the platelet progeny could establish hemostasis in vivo. A lentivirus transfer vector equipped with the human ITGA2B gene promoter confined transgene expression to the platelet lineage. Human ␤3 formed a stable complex with murine ␣IIb, effectively restoring platelet function. Mice expressing significant levels of ␣IIb␤3 on circulating platelets exhibited improved bleeding times. Intravenous immunoglobulin effectively diminished platelet clearance in animals that developed an antibody response to ␣IIb␤3. IntroductionSeveral hundred different proteins orchestrate the adhesion of platelets to the exposed extracellular matrices, signal transduction, aggregation, and clot retraction, leading to the formation of a platelet-plug that helps stop the flow of blood from a wound site. At least 5 members of the evolutionarily conserved integrin family of adhesion receptors are present on platelets to aid in these processes including ␣2␤1, ␣5␤1, ␣6␤1, ␣v␤3, and ␣IIb␤3. 1,2 The molecular structure was recently solved for one integrin, ␣v␤3, 3 which directs binding of platelets and a variety of other cell types to vitronectin. Unlike ␣v␤3, integrin ␣IIb␤3 is expressed exclusively on megakaryocytes and platelets (Ϸ 80 000 copies per platelet) 4 due to the presence of promoter regulatory elements that direct high-level, selective transcription of the ITGA2B gene early in megakaryocytopoiesis. 5 ␣IIb␤3 mediates the interaction of activated platelets with multiple adhesive ligands, including fibrinogen, von Willebrand factor (VWF), fibronectin, thrombospondin, and collagen. 2 Upon activation, ␣IIb␤3 changes its shape to bind its ligand with high affinity for effective platelet aggregation and retraction of a fibrin clot to seal a wound. 6,7 Glanzmann thrombasthenia (GT) is a rare autosomal-recessive bleeding disorder resulting from genetic defects of either ITGA2B or ITGB3 that disrupt subunit synthesis, receptor assembly, and/or function, thus preventing ␣IIb␤3 from binding ligands essential for proper platelet aggregation. 8 More than 100 distinct genetic defects have been characterized for GT, occurring with even distribution in both genes. 9 The diagnosis of thrombasthenia, meaning "weak platelets," is based on the demonst...

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Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Bak^a) detectable only in whole platelet assays

Cited by 53 publications

References 26 publications

Platelet Antibody Analysis by Three Different Tests

Platelet Antibody Analysis by Three Different Tests

Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies

Therapeutic expression of the platelet-specific integrin, IIb 3, in a murine model for Glanzmann thrombasthenia

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Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Baka) detectable only in whole platelet assays

Cited by 53 publications

References 26 publications

Platelet Antibody Analysis by Three Different Tests

Platelet Antibody Analysis by Three Different Tests

Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies

Therapeutic expression of the platelet-specific integrin, IIb 3, in a murine model for Glanzmann thrombasthenia

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Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Bak^a) detectable only in whole platelet assays