Pancytopenia due to high 6-methylmercaptopurine levels in a 6-mercaptopurine treated patient with Crohn's disease.
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.
Gilissen
L P L
LP
Department of Gastroenterology and Hepatology, University Hospital Maastricht (azM), P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. lgi@sint.azm.nl
Derijks
L J J
LJ
Verhoeven
H M J H
HM
Bierau
J
J
Hooymans
P M
PM
Hommes
D W
DW
Engels
L G J B
LG
D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015122:Mercaptopurine / Q000009:adverse effects* / Q000097:blood; D008780:Methyltransferases / Q000235:genetics; D010198:Pancytopenia / Q000139:chemically induced*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000097:blood; D013873:Thionucleotides / Q000097:blood
D013873:Thionucleotides; D013868:Thioinosine; C002344:6-methylthiopurine ribonucleoside-5'-phosphate; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase