title: Evaluation of different methods of leukoreduction of donor platelets to prevent alloimmune platelet refractoriness and induce tolerance in a canine transfusion model.
abstract: 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 < or = .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 gamma-irradiated. Although the gamma-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.
authors.affiliation: Puget Sound Blood Center, Seattle, WA 98104-1256, USA. sjslichter@psbc.org
authors.forename: Sherrill J
authors.initials: SJ
authors.lastname: Slichter
authors.forename: Douglas
authors.initials: D
authors.lastname: Fish
authors.forename: V Kraig
authors.initials: VK
authors.lastname: Abrams
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Gaur
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Doug
authors.initials: D
authors.lastname: Bolgiano
mesh_terms: D000818:Animals; D016824:Antigens, Human Platelet / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D002470:Cell Survival; D004285:Dogs; D007108:Immune Tolerance / Q000276:immunology*; D007518:Isoantibodies / Q000097:blood; D010976:Platelet Count; D017713:Platelet Transfusion; D016038:Skin Transplantation / Q000276:immunology
chemical_list: D016824:Antigens, Human Platelet; D007518:Isoantibodies