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

Dig Liver Dis. 2007 Feb;39(2):182-6. doi: 10.1016/j.dld.2006.05.026. Epub 2006 Aug 1.

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.

Publication types

  • Case Reports

MeSH terms

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

Substances

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