Pancytopenia due to high 6-methylmercaptopurine levels in a 6-mercaptopurine treated patient with Crohn's disease.

Abstract

In a 23-year-old female with colonic Crohn's disease 6-mercaptopurine 100 mg daily (1.7 mg/kg) was added to mesalamine and prednisolone therapy because of ongoing disease activity. One month later she had fever and a pancytopenia. 6-methylmercaptopurine ribonucleotides levels were extremely elevated (57,000 pmol/8x10(8) red blood cells) and 6-thioguanine nucleotides levels were subtherapeutically (126 pmol/8x10(8) red blood cells). Genotyping showed a wildtype thiopurine S-methyltransferase TPMT(H/H) (*1/*1) genotype and a wildtype inosine triphosphate pyrophosphatase gene. TPMT and inosine triphosphate pyrophosphatase activity were normal. The pancytopenia recovered spontaneously within a few weeks, parallel with decreasing 6-methylmercaptopurine ribonucleotides levels after interrupting 6-mercaptopurine treatment. Epstein-Barrvirus, Cytomegalovirus and Herpesvirus infections were excluded by serology. This is the first report of pancytopenia due to extremely high 6-methylmercaptopurine ribonucleotides levels. No relation was found with the genotype of TPMT and inosine triphosphate pyrophosphatase enzymes, which play key roles in the thiopurine metabolic pathway. Apparently, 6-methylmercaptopurine ribonucleotides metabolites can cause pancytopenia, as was already known for 6-thioguanine nucleotides.

• Authors: L P L Gilissen, L J J Derijks, H M J H Verhoeven, J Bierau, P M Hooymans, D W Hommes, L G J B Engels
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 39 Issue 2 Pg. 182-6 (Feb 2007) ISSN: 1590-8658 [Print] Netherlands
• PMID: 16880012 (Publication Type: Case Reports, Journal Article)

Chemical References

• Thionucleotides
• Thioinosine
• 6-methylthiopurine ribonucleoside-5'-phosphate
• Mercaptopurine
• Methyltransferases
• thiopurine methyltransferase

Topics

• Adult
• Crohn Disease (drug therapy)
• Female
• Humans
• Mercaptopurine (adverse effects, blood)
• Methyltransferases (genetics)
• Pancytopenia (chemically induced)
• Thioinosine (analogs & derivatives, blood)
• Thionucleotides (blood)