Platelet membrane glycoproteins (GPs) that act as integrins are necessary for the hemostatic function of platelets. Abnormalities of these GPs are associated with hemorrhage and changes in their activation state may be associated with thrombosis. Glanzmann's thrombasthenia (GT) is a rare autosomal recessive hemostatic disorder in which platelets do not aggregate in response to physiologic agonists because the platelet membrane integrin alpha-IIb-beta-IIIa (GPIIb/IIIa) is deficient or dysfunctional. The patient studied has markedly reduced quantities of normal-length GP IIb cDNA and an alternatively spliced GPIIb cDNA product in which a partial deletion of exon 28 has been identified. Genomic DNA had no defects in exon 28 or in flanking introns to explain this unusual splicing. Furthermore, there were no sequence defects in the GP IIb promoter region that might have explained the overall reduction of GP IIb mRNA. Normal individuals are currently being screened to determine whether the alternatively spliced product is a polymorphism or unique to this patient. Platelets vesiculate to produce microparticles (MPs) when activated. MPs express activated integrins which may play a role in hemostasis or thrombosis. Last year we found MPs adsorb to platelets to transfer integrin-associated alloantigens responsible for posttransfusion purpura. This year we determined the physico-chemical and electron microscopic morphologic characteristics of MPs that support their adsorption to intact platelets. In animal experiments we measured intravascular survival of MP components and their organ localization after leaving the circulation under different physiologic circumstances.
