TRANSFUSION MEDICINE Evaluation of different methods of leukoreduction of donor platelets to prevent alloimmune platelet refractoriness and induce tolerance in a canine transfusion model

The effectiveness of different methods of leukoreduction in preventing alloimmune platelet refractoriness was evaluated in a canine model. Platelets from a random donor dog were administered for up to 8 weeks or until platelet refractoriness. Standard (STD; unmodified) platelets were accepted by 14% of recipients (n 7) compared with 14% for centrifuge leukoreduced (C-LR) platelets (n 21) and 31% for filter leukoreduced (F-LR) platelets (n 13; no significant differences). Surprisingly, using both F-LR and C-LR platelets was highly effective (87% acceptance, n 15). Transfusing F-LR/C-LR red blood cells (n 4) or F-LR/C-LR plasma (n 4), along with F-LR/C-LR platelets, did not affect platelet acceptance (100% acceptance). Overall acceptance of F-LR/C-LR platelets was 91% (n 23; P < .05 versus STD, C-LR, or F-LR platelets). F-LR/C-LR transfusions also induced tolerance to subsequent STD platelet transfusions from the same donor (82% acceptance, n 19) as well as to donor skin grafts without recipient immunosuppression (57% acceptance, n 7). To evaluate mechanisms of tolerance induction, FLR/C-LR platelets were -irradiated. Although the -irradiated F-LR/C-LR platelets were uniformly accepted (n 6), tolerance to STD platelets was lost. These data suggest that some allostimulatory white cells are filter adherent, whereas others escape filtration but can be removed by centrifugation and tolerance requires a residual functioning white cell. (Blood. 2005;105:847-854)