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Aims: To assess the prevalence of thrombophilia among Chinese women with venous thromboembolism (VTE) developed during pregnancy., Methods: Based on information from a tertiary teaching unit, all recorded cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) during pregnancy diagnosed between 1997 and 2005, were assessed for prevalence of thrombophilia. Fifty-five healthy women, who had at least one normal pregnancy but without any previous history of VTE, were recruited as controls., Results: A total of 44 subjects completed thrombophilia screening, of whom 5 (11%) were confirmed to have thrombophilia [protein C (PC) deficiency (2), protein S (PS) deficiency (1), combined PC & PS deficiency (1) and antithrombin III deficiency (1)]. Homozygous 5,10-methylenetetrahydrofolate reductase (C677T) gene mutation was found in 6 (14%) subjects but not in the controls. There was no antiphospholipid syndrome, activated PC resistance, factor V Leiden or prothrombin gene mutations., Conclusion: In the Chinese population, PS and PC deficiencies are common thrombophilia for VTE during pregnancy and thrombophilia screening should be recommended in all pregnant women who suffer from VTE., (Copyright © 2012 S. Karger AG, Basel.)

CYP2C9 and VKORC1 genotypes could be used to predict warfarin requirement. The objective was to develop and validate a warfarin dosing algorithm using genetic, clinical and demographic data of Chinese patients from an anticoagulation clinic in Hong Kong. Blood samples were collected from 100 patients on stable maintenance dose of warfarin, recruited from an anticoagulation clinic, for genotyping CYP2C9 and VKORC1. Clinical and demographic data were obtained by face-to-face interview and medical chart review. Data of 80 patients (study cohort) were randomly selected for deriving a dosing algorithm. Comparison between predicted dose and actual stable doses was conducted in a validation cohort (n = 20). Sixty-nine (69%) of all 100 patients were homozygous for VKORC1 1173-TT, 25 (25%) were VKORC1 1173-CT heterozygotes and six (6%) were homozygous for VKORC1 1173-CC. 6 (6%) patients were CYP2C9 1*/3* and 94 (94%) were CYP2C9 1*/1*. CYP2C9 and VKORC1 genotype, age, weight and vitamin K intake were identified by stepwise regression modelling to produce the best model for estimating warfarin dose (R (2) = 68%, P < 0.001). In the validation cohort (n = 20), actual stable dose was significantly associated with predicted dose (R = 0.6, P = 0.005). Five of 11 (45.6%) and 5/9 (55.6%) patients whose mean warfarin requirements were ≤ 3 mg/day and >3 mg/day, respectively, were within <20% of actual doses. In conclusion, a genotype-guided dosing algorithm for warfarin therapy was developed for Chinese patients to explain 68% of dosage variation. The predicted doses differed from the actual doses by no more than 20% in 50% of patients.

Aim: To compare the treatment outcomes of a clinical pharmacist-managed anticoagulation service with physician-managed service in Chinese patients., Methods: A prospective, randomized clinical trial was conducted at the anticoagulation clinic of a teaching hospital in Hong Kong. Patients aged > or = 18 years who would required warfarin therapy for at least 3 months were recruited. Patients were randomized to the pharmacist-managed or physician-managed group. Primary clinical outcome was assessed by the percentage of patient time spent within the target international normalized ratio (INR) range. The incidence of major thromboembolic events (TEs) and major bleeding was assessed as secondary clinical outcomes. The cost per patient per month (cPPPM) was calculated and patient satisfaction was assessed by patient satisfaction questionnaire (PSQ)-18., Results: One hundred and forty-one patients were recruited at the anticoagulation clinic and 137 patients completed the study. Patients in the pharmacist-managed group (n = 68) were in the target INR 64% of patient time vs. 59% in the physician-managed group (n = 69) (P < 0.001). There was no significant difference in incidence of major TEs or bleeding. The cPPPM in the pharmacist-managed group (76 +/- 95 US dollar) (43 +/- 53 British pound) was lower than in the physician-managed group (98 +/- 158 US dollar) (55 +/- 89 British pound) (P < 0.001). The PSQ-18 score of the pharmacist-managed group (3.8 +/- 0.2) was higher than that of the physician-managed group (3.6 +/- 0.3) (P < 0.001)., Conclusion: The pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy.

Objective: To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population., Methods: A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped. Stable warfarin dose data were retrieved from patient medical records., Results: Sixty-nine patients were included in the analysis. VKORC1 haplotypes H1 (group A) and H7 (group B) were most common, accounting for 86% and 13% of all haplotypic variation in this cohort. Patients carrying at least one copy of a VKORC1 group B haplotype (n = 16) required a significantly higher stable warfarin dose (5.17+/-1.53 mg/day) than patients that were homozygous for group A haplotypes (n = 53; 2.93+/-1.22 mg; P < 0.001). In the VKORC1 A/A group, four patients (5.8%) were heterozygous for CYP2C9*3 and had a lower dose requirement (1.94+/-0.43 mg) than patients that exhibited the CYP2C9 *1/*1 genotype (3.01+/-1.23 mg), P = 0.004. In multivariate analysis, VKORC1 and CYP2C9 explained 31% and 7.9% of the variability in warfarin dose, respectively., Conclusions: VKORC1 genotype is the dominant genetic influence on inter-individual variability in warfarin dose in Hong Kong Chinese. The lower mean dose of warfarin in Chinese, relative to Europeans, appears to be a reflection of their preponderance of the 'low-dose' VKORC1 H1/H1 (homozygous group A) genotype.

Background: Multiple factors can affect the anticoagulation effect of warfarin. The objective of this study was to determine the relationship between different clinical factors and outcomes of warfarin therapy in Hong Kong Chinese patients., Methods: The study was conducted at the anticoagulation clinic of the Prince of Wales Hospital from 1 April to 31 December 2003. Clinical data collected included demographics, indications of warfarin, dietary vitamin K consumption, and drug-drug interactions. Blood samples were obtained for the genetic polymorphism analysis of CYP 2 C 9. Linear and multiple regression analysis were used for statistical analysis to determine the correlation between variables and the importance of various factors as the determinants of warfarin dosage requirement., Results: A total of 63 patients were recruited. The mean warfarin dosage was 3.30+/-2.23 mg/day. The warfarin dosage ranged from 0.75 to 12 mg/day. The mean age was 59+/-14 years old. Age, dietary vitamin K consumption, chronic heart failure, atrial fibrillation, hypertension, smoking and drinking status were found to be factors statistically significant affecting warfarin dosage. We detected no single nucleotide polymorphism in CYP 2 C 9 exon 4., Conclusion: Age, dietary vitamin K consumption, warfarin indication for atrial fibrillation, co-morbid with CHF, smoking and drinking status were found to be the factors that affected the warfarin requirement in Hong Kong Chinese patients. However, the genetic polymorphism in exon 4 of CYP 2 C 9 may not be associated with the warfarin sensitivity in this patient population.