CD32‐Mediated Platelet Aggregation In Vitro by Anti‐Thymocyte Globulin: Implication of Therapy‐Induced In Vivo Thrombocytopenia

Induction therapy with polyclonal antithymocyte‐globulin (ATG) is widely used in the prophylaxis and treatment of acute cardiac‐allograft rejection. Thrombocytopenia, however, is a major side‐effect of ATG therapy and its mechanisms are poorly understood. The influence of ATG on platelet aggregation was studied aggregometrically, expression of platelet surface activation antigens CD62P and CD63 was determined by flow cytometry analysis, and electron microscopy was utilized to determine thrombocyte morphology. Treatment of platelets with ATG markedly induced aggregation, whereas OKT3 or anti‐IL‐2R antibodies did not. Furthermore, platelets incubated with ATG featured an up‐regulation of the surface activation markers CD62P and CD63, secretion of platelet‐bound sCD40L (CD154) and increased signs of aggregation in electron microscopy analysis. The capacity of ATG to induce platelet aggregation was completely blocked by antibodies against the low‐affinity Fc IgG receptor (CD32). Since blocking of CD32 abrogates platelet aggregation, we suggest that CD32 plays a crucial role in ATG‐induced thrombocytopenia.

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