On the role of platelet Fc gamma RIIa phenotype in heparin-induced thrombocytopenia.
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.
Brandt
J T
JT
Department of Pathology, Ohio State University, Columbus 43210, USA.
Isenhart
C E
CE
Osborne
J M
JM
Ahmed
A
A
Anderson
C L
CL
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*
D000906:Antibodies; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D006639:Histidine; D006493:Heparin; D001120:Arginine