Agranulocytosis Induced by Overdosage of Mercaptopurine: A Case Report

Drug-induced agranulocytosis (DIAG) is a rare but potentially fatal hematological complication. Thiopurines, such as mercaptopurine (6-MP), are widely used in the treatment of chronic inflammatory bowel diseases (IBD), but can cause myelotoxicity due to the accumulation of active metabolites. We report the case of a 48-year-old woman with ulcerative colitis who developed severe agranulocytosis following an accidental overdose of 6-MP. The patient presented with febrile pancytopenia with a neutrophil count of 0.04 G/L. Bone marrow examination revealed normal cellularity with an inversion of the maturation pyramid of the granulocyte lineage. A treatment combining growth factors (filgrastim) and antibiotics (tazobactam) was initiated, leading to progressive improvement over 5 weeks. The toxicity of 6-MP is mainly due to the accumulation of 6-thioguanine nucleotides (6-TGN). The polymorphism of the gene encoding the enzyme thiopurine S-methyltransferase (TPMT) can influence the risk of myelotoxicity. Two strategies are proposed to minimize this risk: evaluation of TPMT activity with dosage adjustment, or regular monitoring of blood counts with gradual dose increase. This case highlights the importance of rigorous biological monitoring when initiating 6-MP treatment, regardless of the TPMT test. Increased vigilance is necessary when using immunosuppressive drugs in the treatment of IBD to optimize efficacy and minimize toxicity.