Target molecules recognized by platelet-reactive antibodies. The role played by rare platelet-specific antigens as triggers for neonatal alloimmune thrombocytopenia (NATP) will be characterized by studying mother/father pairs of unresolved NATP cases. Recombinant target proteins will be developed to facilitate NATP diagnosis. The biology of a newly identified genetic trait (high-expression of blood group A and B antigens on platelets) and its significance in platelet transfusion and neonatal thrombocytopenia will be examined. The 5b (HNA-3a) neutrophil/platelet alloantigen, a cause of fatal transfusion reactions in patients transfused with anti-5b, will be characterized. Drug-induced immune cytopenia (DIIC) induced by drugs other than heparin. Mechanisms by which drugs induce drug-dependent antibodies, promote binding of these antibodies to their targets and cause blood cell destruction will be examined at a molecular level. The importance of drug metabolites as triggers for these antibodies will be defined. The possibility that drug-dependent antibodies specific for markers on endothelial cells influence the clinical course of DIIC will be explored. Improved methods for diagnosis of DIIC will be developed. Heparin-induced thrombocytopenia/ thrombosis (HIT). Studies will be undertaken in a large cohort of patients suspected of having HIT to resolve the question of whether antibodies specific for IL-8, a CXC chemokine homologous to PF4, have a role in pathogenesis. Pathogenesis of other immune-mediated platelet disorders. Patients with other immune-mediated platelet disorders relevant to the objectives of this grant will be studies as time and resources permit.
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