BLOOD BANK IMMUNODIAGNOSTICS FOR PLATELET PROTEINS

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During the next year in there United States there will be over 4 million units of platelets transfused for a variety of medical reasons. In spite of the remarkable body of knowledge about platelet physiology and biochemistry, efficacy of this blood product in terms of correcting bleeding problems is usually measured according to the platelet count and the bleeding time, both of which can be determined only after the platelets have been transfused. Poor in vivo efficacy and survival correlates with the extent to which the platelets have been activated prior to transfusion. Within the past few years a number of novel platelet proteins have been described which are only found on the surface of activated platelets. One such protein the PADGEM or the GMP-140 protein which is found in the alpha granules but is expressed on the surface of the platelet once this cell has been activated to express its biochemical potential in terms of participating in hemostasis. We are proposing to develop a rapid immunodiagnostic test fr platelet activation during in vitro storage that will measure PADGEM/GMP-140 on the surface of platelets over the time period which this cell is stored in a plastic bag prior to transfusion. In this phase I study we will determine whether the kinetics of appearance of this protein on the platelet surface during storage correlates with the presence of known biochemical markers of platelet activation and the in vivo survival of this cell. If we can show there is correlation between these two observations, we will proceed in Phase II to format a suitable immunoassay for PADGEM/GMP-140 on platelet surfaces for use in the blood bank and to undertake full clinical trials in humans on the usefulness of this assay in terms of predicting the efficacy of transfused platelets to correct bleeding defects.