Rho GTPase inhibitors for refrigerated platelet storage

ABSTRACT The use of platelet transfusions has increased dramatically since 1980s, but a safe, long-term platelet storage method remains missing. Current practice has platelets stored at 20 to 24 C after preparation, which has a limited lifetime up to 5 days primarily due to concerns about bacterial contamination. Refrigerated storage reduces platelet life-span because it causes glycoprotein-Ib (GPIb) receptors to cluster on specific microdomains of the platelet membrane. Recognition of specific glycated/syalylated residues on clustered glycoproteins by macrophage b2 integrins and hepatocyte Ashwell-Morell receptors results in platelet phagocytosis by the host and removal from circulation. Thus, prevention of glycoprotein clustering represents a useful targetfor chemical intervention. Platelet glycoproteins are intimately associated with intracellular cytoskeleton. Their clustering depends on the formation of lipid raft in the platelet membrane which in turn depends on the dynamics of the highly regulated pr