title: On the role of platelet Fc gamma RIIa phenotype in heparin-induced thrombocytopenia.
abstract: Heparin induced thrombocytopenia (HIT) is characterized by the formation of antibodies that activate normal donor platelets in vitro in the presence of heparin. We asked whether the commonly observed donor-specific variation in the platelet aggregation response to HIT antibodies is influenced by the density of Fc gamma RII on platelets or by the Arg/His 131 allelic polymorphism of platelet Fc gamma RII. We found that platelets with His/His 131 Fc gamma RII phenotype were unresponsive to HIT antibody (0/9) whereas platelets with the Arg/Arg 131 phenotype responded well (7/9). His/His 131 platelets were largely unresponsive also to a murine IgG1 antiplatelet monoclonal antibody (UR1) known to activate platelets by Fc gamma RII clustering. We then determined the frequency distribution of Fc gamma RIIa Arg/His 131 phenotypes on a series of 200 patients evaluated for HIT and 100 non-thrombocytopenic hospitalized patients. The frequency of the His/His 131 phenotype was significantly increased (34.4%) in the 96 thrombocytopenic patients with HIT antibody compared to the 104 thrombocytopenic patients without HIT antibody and the 100 non-thrombocytopenic patients (approximately 19%). Thus, the Fc gamma RII phenotype regulates the in vitro activation response of normal platelets to HIT antibody and is a risk factor for the thrombocytopenia of HIT.
authors.affiliation: Department of Pathology, Ohio State University, Columbus 43210, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Brandt
authors.forename: C E
authors.initials: CE
authors.lastname: Isenhart
authors.forename: J M
authors.initials: JM
authors.lastname: Osborne
authors.forename: A
authors.initials: A
authors.lastname: Ahmed
authors.forename: C L
authors.initials: CL
authors.lastname: Anderson
mesh_terms: D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001120:Arginine; D001483:Base Sequence; D005838:Genotype; D006493:Heparin / Q000009:adverse effects*; D006639:Histidine; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000235:genetics*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D006639:Histidine; D006493:Heparin; D001120:Arginine