Immunogenicity and Stability of Lyophilized Platelets for Transfusion Medicine.

摘要

This project was focused on further development of our technique to stabilize platelets with light fixation and then freeze-dry for long term storage. The stabilization conditions have been well-established as optimized and now the whole process has been scaled up to produce full transfusion doses for use in animal studies or for other preclinical work in the pursuit of an IND with the FDA. The specific aims were directed at investigating the ability of rehydrated lyophilized platelets (RLP) to mount an activation response, to interact with fresh platelets and thereby boost functionality, to generate a near-normal clot signature in vitro, and to restore hemostasis in swine receiving a wash-out' with an artificial hemoglobin solution. In addition, the immunogenicity of canine platelet freeze-dried preparations was tested with multiple infusions in recipient animals. The results demonstrated phosphorylation and other activation-related activities in RLP upon stimulation with physiologic agonists, enhanced adhesion to thrombogenic surfaces in the presence of a small number of fresh platelets, and effective hemostatic activity in the Clot Signature Analyzer in vitro and in the washout swine model in vivo, with very good tolerance of repeated RLP infusions. These findings support the notion that RLP should proceed to an FDA application for clinical trials.