Mean platelet size related to glycoprotein-specific autoantibodies and platelet-associated IgG

Recent evidence suggests that platelet-associated glycoprotein-specific (GP) antibodies represent true positive autoantibodies and can therefore be taken as the gold standard. Earlier tests, which aimed at detecting platelet-associated IgG (PA-IgG), might have been hampered, e.g. by the variation of platelet size in thrombocytopenic patients. In this study, 206 samples with increased PA-IgG from consecutive thrombocytopenic patients were tested further for GP-specific antibodies with a monoclonal antibody immobilized platelet antigen test (MAIPA) using a combination of a GP IIbIIIa-specific and a GP IbIX-specific antibody for immobilization or, in a separate assay, GP V-specific antibody. Mean platelet size was recorded as forward scatter (FSC) of platelets in flow cytometric analysis of PA-IgG. GP-specific antibodies were detected in 49 (24%) of the 206 patient samples. Their presence correlated well with increased PA-IgG (R = 0.769). The mean platelet size and mean fluorescence intensity (MFI) of PA-IgG were both significantly increased in patients compared with healthy controls (n = 112; P < 0.0001). Notably, PA-IgG was associated with platelet size within the platelet population of both healthy controls and patients (R = 0.999). Further, the probability of GP IIbIIIa and/or IbIX and GP V-specific PA-IgG tended to increase with the mean platelet size of the patients (P = 0.045). In conclusion, large platelets bound more IgG than platelets of normal size, which may explain at least in part the reported low specificity of total PA-IgG measurement. As the PA-IgG displays low specificity compared with the gold standard, its use as such may be abandoned and replaced by tests for platelet-associated GP-specific autoantibodies.