title: Fetal bleeding in neonatal alloimmune thrombocytopenia mediated by anti-PlAl is not associated with inhibition of fibrinogen binding to platelet GPIIb/IIIa.
abstract: Antibody directed against the platelet-specific alloantigen, PlAl, is the most frequently reported cause of two syndromes, post-transfusion purpura (PTP), and neonatal alloimmune thrombocytopenia (NAIT). Numerous reports have indicated that anti-PlAl also has the ability to block certain responses of platelets to stimulation, including fibrinogen binding, platelet aggregation, and serotonin release. Because the PlAl epitope is located on platelet membrane glycoprotein (GP) IIb/IIIa that also contains the fibrinogen receptor, these effects may be mediated by antibody binding at or near the fibrinogen receptor site. This study examines the capacity of anti-PlAl from patients with PTP and from mothers of infants affected by the NAIT to block the binding of radio-labeled fibrinogen to washed human platelets stimulated by ADP and epinephrine. In six of the seven PTP patients, there was inhibition of fibrinogen binding, ranging from 28% to 84% inhibition. In contrast, all anti-PlAl sera from nine mothers of infants with NAIT, including four with intracranial hemorrhage, failed to inhibit fibrinogen binding. Despite the generally higher anti-PlAl titers of the PTP sera, the ability to inhibit fibrinogen binding did not appear attributable to antibody titers. These results suggest that interference with fibrinogen binding to platelets by maternal anti-PlAl does not underlie the increased risk of bleeding in NAIT, whereas inhibitory activity directed against fibrinogen binding appears to be a characteristic feature of the sera from PTP patients.
authors.affiliation: Department of Pathology, State University of New York Health Science Center at Syracuse 13210, USA.
authors.forename: W V
authors.initials: WV
authors.lastname: Beadling
authors.forename: J H
authors.initials: JH
authors.lastname: Herman
authors.forename: M J
authors.initials: MJ
authors.lastname: Stuart
authors.forename: M
authors.initials: M
authors.lastname: Keashen-Schnell
authors.forename: J L
authors.initials: JL
authors.lastname: Miller
mesh_terms: D016824:Antigens, Human Platelet / Q000276:immunology*; D001327:Autoimmune Diseases / Q000151:congenital* / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013921:Thrombocytopenia / Q000151:congenital* / Q000276:immunology*
chemical_list: D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen