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Temporary interruption of anticoagulation therapy is usually recommended for anticoagulated patients undergoing invasive procedures to minimize their bleeding risks. We validated the current consensus recommendation on warfarin interruption which were based on Western population studies to determine if they could safely be applied to Asians. The international normalized ratios (INR) in twenty warfarinised patients with a stable INR of 2-3 were prospectively measured at days 0, 3 and 5 after stopping warfarin for procedures or at completion of treatment. The median INR at days 0, 3 and 5 were 2.30 (95% CI 2.16-2.43), 1.32 (95% CI 1.22-1.57) and 1.06 (95% CI 1.05-1.13) respectively (P < 0.001 for trend). All patients were below therapeutic INRs by day 3 with 14 patients (70%, 95% CI 49.92-90.08) achieving INR readings below 1.5. By day 5, all INRs were below 1.5 and only 2 patients (10%, 95% CI -3.15 to 23.15) had INRs above 1.2. There were no significant peri-procedure bleeding or thrombotic events in the 1 month following interruption of warfarin. Our results suggest that the current international recommendation of stopping warfarin for 5 days prior to procedure can safely be applied to Asians without compromising risk of bleeding or thrombosis.

What Is Already Known About This Subject: Recent studies on pharmacogenetics of warfarin have implicated apolipoprotein E (APOE) polymorphisms to influence the vitamin K dependent coagulation cascade and hence the efficacy of warfarin. Studies among Caucasian and African Americans showed a significant but conflicting role of apolipoprotein E (APOE) isoforms in warfarin pharmacogenetics. The contribution of APOE isoforms in influencing variations in warfarin requirements in Asian subjects remains to be investigated., What This Study Adds: This is the first report of a population study in Asians exploring the role of isoforms encoded by three APOE alleles (epsilon 2, epsilon 3, epsilon 4) in influencing warfarin dose requirements. The present study showed that the APOE epsilon 3/epsilon 3 isoform is the predominant genotype in the Asian population. The study also showed that APOE isoforms may not be important in affecting warfarin pharmacodynamics in Asian patients. It also suggested that the impact of different APOE isoforms depended on the frequency of APOE genotypes in the population, in particular the epsilon 4 allele containing genotypes., Aims: To investigate the influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients., Methods: A total of 174 Asian patients (Chinese, n = 96; Malays, n = 50; Indians, n = 28) who had stable daily warfarin doses for at least 1 month were recruited. Following genomic DNA extraction from venous blood, pharmacogenetic analysis of APOE and VKORC1 genes was done by DNA sequencing., Results: The majority of the Asian patients (78%) harboured the APOE epsilon 3/epsilon 3 genotype. Different APOE genotypes were found not to have any significant influence on mean daily warfarin dose requirements. Warfarin dose requirements in the pooled Asian patients homozygous for the VKORC1 H1 haplotype were significantly lower compared with patients homozygous for the H7 haplotype (H1-H1 vs. H7-H7: 2.79 +/- 1.06 mg day(-1)vs. 5.45 +/- 2.3 mg day(-1), P < 0.001)., Conclusions: The present study suggests that APOE variants have minimal impact on warfarin dose requirements in Asian patients, probably due to the low frequency of epsilon 4 allele containing genotypes.