Grant: Operating Grant - Priority Announcement: Blood Utilization and Conservation

Platelets are tiny cells in our blood circulation that act like band-aids to stop us from bleeding. Anyone with low platelet counts may thus have an increased risk of bleeding and if a bleed occurs into the brain, it is almost always severely debilitating or fatal. For example, patients with leukemia have low platelet counts and need to be routinely transfused with platelet transfusions to increase their counts. Studies have shown that platelet transfusions stimulate the development of antibodies in approximately 20 percent of transfused patients. The antibodies bind to platelets in subsequent transfusions and cause their premature destruction. These patients are termed refractory and are very difficult to manage clinically and are at constant threat of severe bleeding. Thus, it would be advantageous to develop more effective therapies that increase platelet counts in these transfusion recipients. On the other hand, some people have an autoimmune bleeding disease called immune thrombocytopenia (ITP) where they make platelet antibodies against their own platelets. The antibodies bind to the patient's own platelets and cause their increased destruction leaving the patient susceptible to bleeding. We have developed animal models that appears to mimic platelet refractoriness and chronic ITP. The proposed research will resolve several mechanistic questions relevant to not only how people respond to platelets but also to how the platelets are destroyed. The information we derive from this work will help us to develop new therapies for these serious bleeding disorders.