Target molecules recognized by platelet-reactive allo- and isoantibodies. The relevance of a newly identified genetic trait (high-expression of blood group A and B antigens on platelets) to platelet transfusion effectiveness, neonatal alloimmune thrombocytopenia (NATP), and transfusion reactions will be explored. The significance of the Gova/b platelet alloantigen system in NATP will be examined. Isoimmunization to platelet glycoprotein IV (GPIV) as a cause of platelet transfusion refractoriness in African-American patients will be further defined. Immune thrombocytopenia induced by drugs other than heparin. Mechanisms by which drugs induce immune-mediated thrombocytopenia (DITP) and the molecular basis for drug-platelet-antibody interaction in DITP will be characterized. The importance of drug metabolites as triggers for DITP and the need to use metabolites for detection of drug-induced antibodies will be defined. Mechanisms by which newly developed GPIIb/IIIa inhibitors cause thrombocytopenia in a significant fraction of treated patients and the significance of """"""""naturally occurring"""""""" antibodies reactive with activated GPIIb/IIIa will be examined. Heparin-induced thrombocytopenia/thrombosis (HITT). The molecular basis of the immune response to complexes containing heparin and platelet factor 4 (PF4) in patients with HITT will be characterized with emphasis on T-cell receptor (TCR) utilization and target epitopes recognized. Pathogenesis of other immune-mediated platelet disorders. Patients with other immune-mediated platelet disorders relevant to the objectives of this grant will be studied as they are encountered.
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