Azathioprine-induced fatal macrocytic anemia in rabbits

Azathioprine (AZA) is used clinically sometimes at high doses for short-term therapy to treat acute rejection of kidney allograft or to desensitize hypersensitive patients to it. The delayed consequences of this approach had not been well investigated. Therefore, in this study we have investigated the delayed consequences of high-dose short-term AZA administration in rabbits. Our results showed that oral administration of AZA (10 mg/kg/day) to rabbits for two weeks induced reversible thrombocytosis and delayed fatal macrocytic anemia. Moreover, neither the hemoglobin level nor the white blood cell count was affected by AZA. The solvent of AZA had no effect on blood cell counts and hemoglobin levels. We can conclude that although high-dose AZA therapy may not induce immediate and significant changes in blood picture, delayed fatal macrocytosis may occur.