title: Predictors of warfarin dose requirements in South African patients attending an anticoagulation clinic.
abstract: BACKGROUND
  Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors.
  
  
  METHODS
  This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital.
  
  
  RESULTS
  The most common indication for anticoagulation was atrial fibrillation (n = 55, 37.4%). The mean warfarin dose was significantly higher in black patients as compared to white patients (5.4 ± 2.9 mg/day and 3.8 ± 2.1 mg/day, respectively; P < 0.001). Older age was significantly associated with a lower maintenance warfarin dose (P < 0.001). Drugs which decreased the international normalized ratio (INR) were significantly associated with a higher maintenance warfarin dose of 6.4 ± 3.4 mg/day (P < 0.034). In contrast, there was no significant difference in warfarin dosage requirements in the presence of CYP2C9 and VKORC1 variant alleles (P > 0.05). Patients, however, homozygous for CYP2C9 *1,*3, and VKORC1 required less than 5 mg/day of warfarin to maintain the INR within the therapeutic range.
  
  
  CONCLUSIONS
  In conclusion, this study indicates that clinical characteristics including; age, ethnic group, and drugs which decrease the INR might help to predict better dose requirements in this population group and thereby reduce the risk of bleeding and thrombotic complications.
authors.affiliation: Department of Molecular Medicine and Hematology, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Anticoagulation Clinic and University of Witwatersrand, Johannesburg, South Africa. Electronic address: elise.schapkaitz@nhls.ac.za.
authors.forename: Elise
authors.initials: E
authors.lastname: Schapkaitz
authors.affiliation: Department of Molecular Medicine and Hematology, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Anticoagulation Clinic and University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sithole
mesh_terms: D000367:Age Factors; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy; D001777:Blood Coagulation / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D004347:Drug Interactions / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013019:South Africa; D013923:Thromboembolism / Q000208:ethnology / Q000517:prevention & control*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases