title: Exacerbation of hereditary warfarin resistance by azathioprine.
abstract: A 39-year-old Afro-Caribbean man with Crohn disease with recurrent deep vein thromboses and pulmonary emboli was commenced on lifelong warfarin treatment. The patient required high-dose warfarin (>140 mg/wk), which increased further during azathioprine treatment. Cessation of azathioprine resulted in an increase in the international normalized ratio (INR). Mutation analysis identified a Val66Met substitution in vitamin K epoxide reductase complex subunit 1 (VKORC1), consistent with severe warfarin resistance. This report is the first presentation where the patient had a defined hereditary resistance to warfarin, which was aggravated by concomitant azathioprine. It is important for clinicians to be aware of the interaction between warfarin and azathioprine, to monitor clinical response closely, and to manage the doses of both drugs accordingly.
authors.affiliation: Department of Medical Genetics, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom.
authors.forename: Sudeep P
authors.initials: SP
authors.lastname: Pushpakom
authors.forename: Nikki
authors.initials: N
authors.lastname: Gambhir
authors.forename: Ayshe
authors.initials: A
authors.lastname: Latif
authors.forename: Kristen D
authors.initials: KD
authors.lastname: Hadfield
authors.forename: Simon
authors.initials: S
authors.lastname: Campbell
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000925:Anticoagulants / Q000008:administration & dosage*; D000963:Antimetabolites / Q000008:administration & dosage*; D001379:Azathioprine / Q000008:administration & dosage*; D003424:Crohn Disease; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020125:Mutation, Missense; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D000963:Antimetabolites; D014859:Warfarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D001379:Azathioprine