Platelet antigens. The role of human platelet alloantigens (HPA) in blood transfusion and transplantation.

In this review, we describe the platelet surface molecules with special focus on the polymorphic glycoproteins giving rise to the human platelet alloantigen (HPA) system. We list the platelet glycoprotein complexes GPIa/IIa, GPIIb/IIIa, GPIb/V/IX and some other molecules, the corresponding genes that encode them and we describe their polymorphisms as well as their physiological function. Based on data obtained by serological and molecular methods, we explain how ancestral HPA alloepitopes have developed into the modern variants. We also describe the tissue distribution of these proteins, which seems to be wider than thought initially, and discuss the significance of the HPA encoding genes distribution in various populations. Methods for their determination are then described briefly Since HPA alloepitopes can induce antibodies with resulting clinical conditions such as: post-transfusion refractoriness to platelets (PTR); post-transfusion thrombocytopenic purpura (PTTP); and fetomaternal alloimmune thrombocytopenia (FMAIT), the mechanism of this alloimmunization and its prevention is described. Although the humoral arm is more important from the clinical viewpoint, the activation of the cytotoxic arm by HPA alloepitopes is also possible. These polymorphisms also seem to have a role in certain other clinical circumstances, therefore their impact on cardiovascular diseases and haemostatic disorders as well as their role in the transplantation of solid organs and bone marrow is addressed. We conclude that during the last decades, the research of the platelet membrane molecules contributed considerably to the diagnostics, prevention and therapy of the blood coagulation and haemostatic disorders, to the management of the neonatal thrombocytopenias, transfusion-related thrombocytopenias, refractoriness to platelet transfusions and autoimmune disorders. It also changed our view on the role of HPA alloepitopes in bone marrow and solid organ transplantation. In the future, this accumulated knowledge will be useful for the development of the cell-based therapies and immune modulation of both acquired and hereditary diseases.