Synergistic action in platelet activation induced by an antiplatelet autoantibody in ITP

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Abstract
Summary. We detected an autoantibody which activated normal platelets in a patient with immune thrombocytopenic purpura and investigated the mechanism by which this autoantibody mediated platelet activation. The patient's IgG induced platelet aggregation and ATP secretion in normal platelet‐rich plasma (PRP). IgG‐induced aggregation was inhibited by aspirin (ASA), apyrase, a protein kinase C (PKC) inhibitor and two anti‐platelet glycoprotein (GP) IIb/IIIa monoclonal antibodies. The increase of aequorin‐detected intraplatelet Ca2+ induced by the patient's IgG was extremely slight. Phosphorylation of a 40 kDa protein was induced by the patient's IgG without any obvious phosphorylation of a 20 kDa protein, and was inhibited by a PKC inhibitor but not by ASA. With ASA‐treated normal PRP, the patient's IgG failed to induce aggregation itself, but enhanced ADP‐ or STA2‐induced aggregation. Western blotting and immuno‐precipitation experiments showed that the patient's IgG reacted to a protein of 36 kDa. These results suggest that the platelet activation induced by this autoantibody depended on both the selective activation of PKC and the slight Ca2+ mobilization induced by thromboxane A2 synthesis, while the aggregation depended on secretion induced by the synergistic action of the above two mechanisms and was mediated through GP IIb/IIIa.