Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Kleinman, Steve; Stassinopoulos, Adonis

As mentioned, two SCD patients in a first-generation S-303 and GSH Phase III trial developed antibodies; these were found to be directed against adducts formed on the RBC surface during S-303 treatment. Further characterization of the antibodies showed they were low titer (2) (3) (4) (5) (6) (7) (8) , were inhibited by acridine compounds (thereby pinpointing specificity for the anchor part of the S-303 molecule), and did not cause phagocytosis of S-303-treated RBCs in an in vitro model of RBC clearance. 134 In a rabbit mismatch transfusion model, 135 first-generation S-303 RBCs circulated normally in naive animals and did not cause the formation of antibodies. However the S-303 RBCs showed accelerated clearance when the animals were immunized with KLH-acridine compounds. These observations led to the technology modifications incorporated in the second-generation system. When secondgeneration S-303 RBCs were transfused to the same preimmunized animals, they exhibited normal circulation. Finally, sera from the two antibody-positive patients were negative when cross-matched against second-generation S-303 RBCs.