An animal model of alloimmune thrombocytopenia: I. The role of the mononuclear phagocytic system (MPS)

To understand better the role of the mononuclear phagocytic system (MPS) in accelerated destruction of donor platelets in man following repeated platelet transfusions, an experimental model has been developed using genetically defined animals. Brown Norway rats were immunized with Lewis platelets. Antibodies were detected by immunofluorescence microscopy, and their effects demonstrated by 111In-labeled platelet clearances in vivo and by measurements of organ radioactivity in sacrificed animals. All immunized rats developed platelet alloantibodies and showed a significant decrease ( P < 0.001) in donor platelet survival with sequestration in both the liver and spleen. Liver to spleen radioactivity ratios in nonimmunized animals were less than 0.1, whereas immunized animals had a ratio between 0.6 and 1.0, indicating relatively greater hepatic clearance of allogenic platelets. Studies currently in progress on the administration of vinca alkaloids to immunized animals suggest that the MPS can be impaired from clearing allogenic platelets. This model, therefore, should be helpful in studying the role of the MPS in platelet destruction.