Submitted August 27, 2003
Accepted May 29, 2004
Evaluation of different methods of leukoreduction of donor platelets to prevent alloimmune platelet refractoriness and induce tolerance in a canine transfusion model
Sherrill J Slichter*, Douglas Fish, V Kraig Abrams, Lakshmi K Gaur, Karen Nelson, and Doug Bolgiano
Research Division, Puget Sound Blood Center, Seattle, WA, USA
University of Washington School of Medicine, Seattle, WA, USA
* Corresponding author; email: sjslichter{at}psbc.org.
The effectivness 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 8 weeks or until platelet refractoriness. Acceptance rates were 14% for standard (STD) (unmodified) platelets (n=7), 14% for centifuge leukoreduced (CLR) platelets (n=21), and 31% for filter leukoreduced (F-LR) platelets (n=13), no significant differences. Surprisingly, combining F-LR and C-LR 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 compromise the effectiveness of F-LR/C-LR platelets (both 100% acceptance). The overall acceptance rate for F-LR/C-LR platelets was 91% (n=23) (p=<0.05 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, F-LR/C-LR platelets were g-irradiated. Although the g-irradiated F-LR/C-LR platelets were still accepted (100% acceptance, n=6), tolerance to STD platelets was lost. These data suggest that some allostimulatory white cells are filter adherent while others escape filtration but can be removed by centrifugation and tolerance requires a residual functioning white cell.
