Background And Objectives: This report describes the production of a freeze-dried preparation of pooled human plasma, containing immunoglobulin G (IgG) antibodies against the human platelet antigen 1a (HPA-1a). The material, coded 03/152, is proposed as an International Standard containing 100 arbitrary units of anti-HPA-1a for use in quantitative assays to determine the anti-HPA-1a activity in clinical samples.

Materials And Methods: Plasma samples containing potent anti-HPA-1a were pooled and freeze dried in 1-ml ampoules. In addition, three individual plasma samples were selected which had varying levels of anti-HPA-1a activity. The anti-HPA-1a activity of these three samples was determined by using a variety of quantitative assays with the proposed standard as a reference.

Results: An international collaborative study, which was part of the 2004 ISBT Platelet Immunology Workshop, involved 39 laboratories in 24 countries and showed that the anti-HPA-1a activity in three test samples could be reliably determined by using the proposed standard.

Conclusions: Laboratories can use this standard to measure the anti-HPA-1a activity in patient's samples. Further studies are required to determine the relationship between anti-HPA-1a activity and clinical outcome in patients with neonatal alloimmune thrombocytopenia (NAIT).

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1423-0410.2005.00669.xDOI Listing

Publication Analysis

Top Keywords

anti-hpa-1a activity
24
anti-hpa-1a
9
collaborative study
8
international standard
8
quantitative assays
8
activity clinical
8
plasma samples
8
activity three
8
activity
6
samples
5

Similar Publications

Cellular surface plasmon resonance-based detection of anti-HPA-1a antibody glycosylation in fetal and neonatal alloimmune thrombocytopenia.

Front Immunol

November 2023

Immunoglobulin Research Laboratory, Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur due to maternal IgG antibodies targeting platelet antigens, causing life-threatening bleeding in the neonate. However, the disease manifests itself in only a fraction of pregnancies, most commonly with anti-HPA-1a antibodies. We found that in particular, the core fucosylation in the IgG-Fc tail is highly variable in anti-HPA-1a IgG, which strongly influences the binding to leukocyte IgG-Fc receptors IIIa/b (FcγRIIIa/b).

View Article and Find Full Text PDF

FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on integrin β3. The clinical effects range from no symptoms to fatal intracranial hemorrhage, but underlying pathophysiological determinants are poorly understood. Accumulating evidence suggests that differential antibody-Fc-glycosylation, activation of complement/effector cells, and integrin function-blocking effects contribute to clinical outcome.

View Article and Find Full Text PDF

Fc galactosylation of anti-platelet human IgG1 alloantibodies enhances complement activation on platelets.

Haematologica

October 2022

Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam.

Approximately 20% of patients receiving multiple platelet transfusions develop platelet alloantibodies, which can be directed against human leukocyte antigens (HLA) and, to a lesser extent, against human platelet antigens (HPA). These antibodies can lead to the rapid clearance of donor platelets, presumably through IgG-Fc receptor (FcγR)-mediated phagocytosis or via complement activation, resulting in platelet refractoriness. Strikingly, not all patients with anti-HLA or -HPA antibodies develop platelet refractoriness upon unmatched platelet transfusions.

View Article and Find Full Text PDF

Prospects for risk stratification of anti-HPA-1a alloimmunized pregnant women.

Transfus Apher Sci

February 2020

Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany; Center for Transfusion Medicine and Hemotherapy, University Hospital Giessen and Marburg, Marburg, Germany; German Center for Fetomaternal Incompatibility (DZFI), University Hospital Giessen and Marburg, Giessen, Germany. Electronic address:

A diagnosis of fetal/neonatal alloimmune thrombocytopenia (FNAIT) is made if a platelet-specific antibody is detected in the mother and the fetus or newborn carries the cognate antigen. Some children will experience very low platelet counts or even intracranial hemorrhage with devastating consequences, whereas others are largely unaffected. At the moment, predictive tools to forecast the severity of FNAIT during pregnancy are not available and over- or under-treatment may put the mother or the fetus at risk.

View Article and Find Full Text PDF

Integrin α/β heterodimer adopts a compact bent conformation in the resting state, and upon activation undergoes a large-scale conformational rearrangement. During the inside-out activation, signals impinging on the cytoplasmic tail of β subunit induce the α/β separation at the transmembrane and cytoplasmic domains, leading to the extended conformation of the ectodomain with the separated leg and the opening headpiece that is required for the high-affinity ligand binding. It remains enigmatic which integrin subunit drives the bent-to-extended conformational rearrangement in the inside-out activation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!