This Phase I project proposes to systematically examine whether complement activation plays a significant role in the platelet storage lesion (PSL). The goals of the project are four-fold: (1) to assess the etiology of PSL by depleting complement factor 8 from platelet storage plasma; (2) determine if monoclonal antibodies directed against C8 or C9 inhibit the PSL; (3) determine if CD59, a naturally occurring inhibitor of the assembly of terminal complement components can attenuate the development of PSL; and (4) based on results obtained in 1-3, determine whether any of these approaches will arrest the development of PSL in platelet concentrates prepared and stored using FDA approved blood bank procedures. A clear demonstration of a complement-mediated component in PSL would ultimately lead to Phase II testing of complement inhibiting agents in platelet concentrate preparations and an assessment of platelet survival. Accordingly, the proposed Phase I studies, if successful, have a clear connection to Phase II studies.
