INFUSIBLE PLATELET MEMBRANE MICROVESICLES - A POTENTIAL TRANSFUSION SUBSTITUTE FOR PLATELETS

Background: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varie d success. Infusible platelet membrane (IPM) is prepared from human pl atelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, seroton in, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPI Ib/IIIa complex, and HLA class I and II antigens are all absent in IPM . Study Design and Methods: IPM is prepared from outdated platelets. T he platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the son icated membrane microvesicle fraction was separated and, lyophilized. The hemostatic activity of IPM was measured by its ability to reduce t he prolonged bleeding time in thrombocytopenic rabbits. Results: Admin istration of IPM at a dose of 2 mg per kg results in a substantial red uction in the bleeding time. In a series of 23 experiments, a median p reinjection bleeding time of 15 minutes was reduced to 6 minutes withi n 4 hours after IPM administration. Administration of IPM did show a m ild enhancement in the thrombogenicity index, as measured in the Wessl er rabbit model. This enhancement is, however, not significant, as a t hrombogenicity index value of up to 0.6 is clinically acceptable. Conc lusion: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.