In summary, the search for a useful clinical laboratory diagnostic assay for the antiplatelet
antibodies has been long and difficult. Measurement of platelet associated
IgG (PAIgG) has been disappointing as a way to detect
autoantibodies. This is primarily due to the fact that platelets normally contain
IgG in their alpha granules in an amount that varies with plasma
IgG levels and age of the platelets. Furthermore, the amounts of platelet associated
IgG is affected by the presence of circulating
immune complexes, platelet activation, and
drug dependent
antibodies. The newer, platelet
antigen capture techniques are promising, but further testing will be needed to confirm their value to the clinician. Methods that allow incubation of patient serum or plasma with intact platelets (MAIPA and immunobead) have greater sensitivity than techniques in which the patient antibody is tested against previously isolated
platelet glycoproteins. These assays are currently available in a only a limited number of platelet immunology laboratories. Platelet
autoantibodies are directed against a number of
glycoprotein antigens on the platelet surface. Most studies have shown that anti GPIIb/IIIa
antibodies are the most common, although
antibodies against GPIb/IX and other targets are frequently detected. Many patients have multiple antiplatelet
antibodies circulating simultaneously. The clinical significance of
antibodies with different specificity is under investigation. The precise
epitopes on
GPIIIa that bind antiplatelet
autoantibodies have been studied to a limited extent. Some investigators report that the vast majority of platelet
antigens are conformation dependent, being destroyed by treatment with
EDTA (separation of GPIIb and
GPIIIa) or denaturation with
detergents. Others report sequence specific
peptide antigens. Further investigation promises to better define the targets for platelet
autoantibodies; improved clinical management of patients with
ITP is the long term goal of these studies.