PHOTOINACTIVATION OF VIRUSES IN PLATELET SUSPENSIONS

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Transmission of infection is the most frequent and serious negative outcome of blood transfusion, despite extensive donor screening and laboratory testing. It is estimated that up to 100 recipients of blood and its components may be infected with HIV in the United States each year and prospective studies have been interpreted to suggest that up to 300,000 recipients may be infected have hepatitis viruses that have a potential for causing serious or lethal long term sequelae. Herpes viruses continue to be a problem for immunocompromised recipients and newly recognized retroviruses are generating concern. Among recipients of blood components, approximately 250,000 patients receive platelet concentrates annually; most of these recipients are under treatment protocols which result in profound immunosuppression. The nature of platelet concentrates does not permit simple physical methods of removing infectious contaminants. Certain photoinactivation procedures are specific for nucleic acids; preliminary investigations suggest that conditions which inactivate 5-6 logs of model viruses do not interfere with platelet function. Safe, effective photoinactivation protocols will be developed to inactivate 6 logs of HIV in both plasma and cellular compartments in platelet concentrates. These methods will be evaluated and modified as appropriate to eliminate 5-6 logs of more resistant model viruses. Screening methods will be used to assess the separate effects of photoinactivators and long-wave UV on viruses and platelets in controlled conditions. Conditions which inactivate 6 logs of virus but retain platelet morphology will be investigated in more depth in a platelet concentrate environment to assess mechanisms of platelet damage and to understand the kinetics and mechanism of nucleic acid damage in this milieu. Toxicologic studies will be carried out so that delivery methods, can, if necessary, be designed to incorporate means to remove added chemicals.