PHOTOCHEMICAL TREATMENT OF PLATELET CONCENTRATES WITH A NOVEL PSORALEN AND UVA TO ENHANCE THE SAFETY OF PLATELET TRANSFUSIONS

Background: To enhance the safety of platelet transfusions, a photoche mical treatment (PCT) process utilizing a novel psoralen (S-59) in con junction with long wavelength ultraviolet light (UVA, 320-400 nm), has been developed for inactivation of viruses and bacteria in platelet c oncentrates. Materials and Methods: Viral and bacterial stocks of high infectivity were added to single-donor platelet concentrates containi ng 3-5 x 10(11) platelets in 300 ml of 35% autologous plasma and 65% p latelet additive solution (PASIII). For clinical HIV isolates the high est titered available viral stacks were used. After PCT with S-59 (150 mu M) and UVA (0-3 J/cm(2)), the residual infectivity of viruses and bacteria was measured with established assays. In vitro platelet funct ion following PCT with 150 mu M S-59 and 3 J/cm(2) UVA and subsequent S-59 removal was evaluated during 7 days of storage by a panel of 13 a ssays Antibodies against PCT platelets and plasma proteins in suspensi on medium were raised in rabbits to assess whether PCT induces neoanti gen formation. Results: The following levels of reduction in infectivi ty of viruses and bacteria were obtained: >10(6.6) pfu/ml of cell-free and cell-associated HIV-1 (strain IIIB), >10-(3.4) tissue culture inf ections dose (TCID50)/ml of a clinical isolate of HIV-1, >10(2.5) TCID 50/ml of a clinical isolate of HIV-2, 10(6.8) infectious dose (ID50)/m l of duck hepatitis B virus, >10(6.5) pfu/ml of bovine viral diarrhea virus, >10(6.4) pfu/ml of cell-associated human cytomegalovirus, >10(6 .3)-fold reduction of five strains of Gram-positive bacteria, and 10(4 .5)- to >10(6.7)-fold reduction of seven strains of Cram-negative bact eria. The proviral form of HIV-1(IIIB) was also sensitive to inactivat ion. In vitro platelet function was not adversely affected following P CT and S-59 removal during 7 days of storage. In addition, immunologic al studies have demonstrated the absence of neoantigens following PCT of platelet concentrates. Conclusion: Photochemical treatment of plate let concentrates with S-59 and UVA offers the potential to reduce tran sfusion-related viral and bacterial diseases in transfusion recipients .