Approaches to preventing or reversing platelet alloimmunization using animal models.

Animal transfusion models were established to assess treatment programs for preventing or reversing platelet alloimmunization. Five control baboons given weekly transfusions of radiolabeled platelets from a single unrelated donor became immunized after an average of 2.4 +/- 2.1 transfusions. Similarly, 18 of 21 (86%) dogs given up to eight platelet transfusions from a single unrelated donor became immunized after an average of 2.3 +/- 1.7 transfusions. In six of seven baboons, prednisone or antithymocyte globulin alone or in combination effectively delayed platelet alloimmunization. In contrast, only two of 12 (17%) dogs given prednisone or antithymocyte serum (ATS) resisted alloimmunization. Neither splenectomy nor cyclophosphamide prevented alloimmunization in the baboon. In addition, attempts to reduce the immunogenicity of transfused platelets by inactivating the contaminating leukocytes with gamma radiation or by giving leukocyte-poor platelets were of no benefit in dogs. Reversal of platelet alloimmunization was achieved in two of three dogs treated with ATS and procarbazine hydrochloride. However, neither splenectomy, cyclophosphamide, ATS plus prednisone, nor vincristine sulfate produced any improvement. These studies show that the highly immunogenic nature of platelet transfusions in animals makes feasible the study of the prevention and reversal of platelet alloimmunization.