Hemorrhagic Diseases

Versiti Wisconsin, Inc., Milwaukee WI

Investigators

Linked publications, trials & patents

Abstract

Target molecules recognized by platelet-reactive antibodies. The role of low frequency platelet-specific antigens as triggers for neonatal alloimmune thrombocytopenia (NATP) will be characterized more fully. Improved methods for detecting and identifying the responsible antibodies will be developed. The significance of [unreadable]high-expression[unreadable] of A/B antigens on platelets in NATP and other aspects or transfusion medicine will be defined. Molecular properties of the HNA-3a neutrophil antigen, an important trigger for transfusion-related acute lung injury (TRALI) will be determined. Drug-induced immune thrombocytopenia (DITP) (non-heparin). Mechanisms by which drugs induce drug-dependent antibodies (DDAbs) and promote binding of DDAbs to their targets will be characterized at the molecular level using both human DDAbs and murine monoclonal DDAbs that mimic their human counterparts. A unique NOD/scid mouse model will be used to define mechanisms of in vivo destruction of human platelets by human and murine DDAbs and to characterize drug metabolites capable of triggering DITP. A murine model of DITP will be explored. Pathogenesis and clinical aspects of the drug-induced hemolytic syndrome will be examined. Heparin-induced thrombocytopenia (HIT). Clinical significance of HIT antibody isotypes, correlations between serologic findings and risk of thrombosis, possible role of IL8-specific antibodies, pathogenesis of [unreadable]delayed[unreadable] HIT and other unresolved issues concerning HIT will be addressed in a clinical/lab environmental highly favorable for this type of investigation. Pathogenesis of other types of immune-mediated thrombocytopenia. Patients with other immune-mediated platelet disorders will be studied as time and resources permit. Relevance. Immune-mediated blood disorders are a major cause of morbidity and mortality. The proposed studies will lead to a better understanding of causation and improved diagnosed and treatment.