title: Decrease in factor V activity in patients treated with azathioprine or 6-mercaptopurine.
abstract: OBJECTIVE
  A decrease in factor V activity has been reported in some patients treated with azathioprine or 6-mercaptopurine. This may lead to unnecessary treatment discontinuation in otherwise asymptomatic patients. Our aim was to review spontaneously reported cases of decreased factor V activity associated with both drugs and to identify the possible impact on patient care.
  
  
  METHODS
  Cases of decrease in prothrombin (PT) or factor V activity involving purine analogs were extracted from the French pharmacovigilance database. Reports with evidence of disseminated intravascular coagulation, signs of acute hepatocellular failure, liver cirrhosis or concomitant vitamin K antagonist treatment were excluded.
  
  
  RESULTS
  Twenty-four cases (azathioprine: 13 and 6-mercaptopurine: 11) were retained. Therapeutic indications were inflammatory bowel diseases in 11 patients, acute leukemia in eight, and other autoimmune diseases in five. PT activity before treatment was normal in all nine tested patients. The decrease in PT or factor V activity occurs after a median of 10 weeks of treatment and all patients were asymptomatic. The median PT and factor V activities values were 51.5% and 36.4%, respectively. Other coagulation factors were inconsistently decreased. Full recovery was observed within 3-60 days following purine analogs discontinuation. In four patients, drug rechallenge was associated with recurrence of the coagulation disorders.
  
  
  CONCLUSIONS
  Although the mechanism remains unknown, this series that includes cases with positive drug reintroduction strongly suggests the causative role of these drugs. As all patients remained asymptomatic, treatment discontinuation should be carefully considered in patients who clearly benefits from this treatment.
authors: Centre régional de pharmacovigilance, 162, avenue Lacassagne, 69003 Lyon, France.
authors: Nathalie
authors: N
authors: Paret
authors: Centre régional de pharmacovigilance, hôpital du Bocage, 10, boulevard Maréchal-de-Lattre-de-Tassigny, BP 77908, 21000 Dijon, France.
authors: Anne
authors: A
authors: Dautriche
authors: Centre régional de pharmacovigilance, service de pharmacologie clinique, hôpital Bretonneau, 2, boulevard Tonnellé, 37044 Tours cedex 9, France.
authors: Annie Pierre Jonville
authors: AP
authors: Bera
authors: Centre régional de pharmacovigilance, 162, avenue Lacassagne, 69003 Lyon, France.
authors: Aurore
authors: A
authors: Gouraud
authors: Centre régional de pharmacovigilance, 162, avenue Lacassagne, 69003 Lyon, France.
authors: Anne
authors: A
authors: Millaret
authors: Centre régional de pharmacovigilance, 162, avenue Lacassagne, 69003 Lyon, France.
authors: Jacques
authors: J
authors: Descotes
authors: Centre régional de pharmacovigilance, 162, avenue Lacassagne, 69003 Lyon, France. Electronic address: thierry.vial@chu-lyon.fr.
authors: Thierry
authors: T
authors: Vial
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C035876:factor V clotting antigen; D005165:Factor V; D015122:Mercaptopurine; D001379:Azathioprine