Effect of ABO Blood Groups on the Response to Warfarin.

BACKGROUND
Numerous studies have demonstrated that patients with non-O blood groups have a higher risk for venous thromboembolism than those with the O blood group. However, the effect of ABO blood groups on warfarin dose requirements in patients receiving anticoagulation in the Chinese Han population remains unknown. This study aimed to investigate the influence of ABO blood groups on warfarin dose requirements in a Chinese Han population.


MATERIAL AND METHODS
A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. Three hundred and fifty-eight patients with a confirmed diagnosis of deep vein thrombosis or atrial fibrillation were included. The frequency of blood groups and warfarin dose requirements were determined.


RESULTS
Of 358 patients with deep vein thrombosis or atrial fibrillation, 111 patients had blood group A (31.01%), 104 patients had blood group B (29.05%), 20 patients had blood group AB (5.59%) and 123 patients had blood group O (34.36%). The patients in the O blood group had lower warfarin dose requirements than those in the A, B and AB blood groups.


CONCLUSIONS
Our study showed that patients with non-O blood groups require higher doses of warfarin.

Conclusion: Our study showed that patients with non-O blood groups require higher doses of warfarin.

Background
Warfarin is the most commonly prescribed oral anticoagulant drug since 1950s [1], which has been widely used to prevent embolic stroke in patients with atrial fibrillation (AF) [2] and treatment of thromboembolic disorders. Despite extensive experience with its use, warfarin still caused a variety of adverse effects because of its narrow therapeutic index [3]. The anticoagulant activity of warfarin is assessed by using the International Normalised Ratio (INR) [4]. Maintaining a patient in the therapeutic range is associated with improved outcomes, with target INR being between 2.0 and 3.0 for most indications.
Subtherapeutic anticoagulation will lead to inadequate protection while supratherapeutic anticoagulation to life-threatening bleeding. Therefore it is important to identify the clinical and genetic predictors of warfarin dose-response in individual patients [5][6][7].
According to previous studies, various factors such as age, gender, body weight and genetic polymorphisms [8][9][10][11] have been reported to be major determinants of warfarin dose requirements. Recently some studies have addressed the potential role of ABO blood groups in deep vein thrombosis (DVT). Compared with O blood group, non-O blood groups have higher risk for DVT [12][13][14]. However, the influence of ABO blood groups on warfarin dose requirements was not well known. In present study we aimed to investigate the Data are presented as the number of patients or mean ± SD. Differences between groups were assessed by Chi-square tests or by ANOVA for multiple comparisons using SPSS 16.0. 4 P value < 0.05 was considered significant.

Results
As shown in the Table 1 and vitamin K epoxide reductase complex subunit 1 gene (VKORC1) genotype status with relevant clinical factors, which can explain 53-54% of the variability in the warfarin dose [7]. In study by Ather et al [16], the algorithm explained only 30% of the variance, which suggested though many factors affecting warfarin dose requirements have been well described, determining more factors is important.
Recently the relationships between ABO blood groups and DVT have been demonstrated.
Compared with O blood group, there is higher risk of venous thromboembolism in non-O blood groups [12][13][14]. Furthermore, the blood group remarkably affected the anesthetic effects of propofol [17]. However, the association of ABO-blood groups with warfarin dose requirements has not been addressed.
In present study, we investigated the possible connection between ABO phenotype and warfarin dose requirements. The study showed that there are lower warfarin dose requirements in patients with O blood type than non-O blood groups. There are no significant differences about warfarin dose requirements among A, B and AB blood group.
To our knowledge, this is the first report to assess the influence of ABO blood group on warfarin dose requirements, the result suggested that ABO blood groups may be as a clinical factor to be included in predicting warfarin dose requirements.
The mechanisms that patients with O blood group had lower warfarin dose requirements have not been fully elucidated. It was reported that body weight contributed to the anticoagulant response to warfarin [10]. In present study the weight in O blood group is lighter than B blood group. However body weight only accounts for about 6.3% of the variability in warfarin dose requirements [10]. Other factors maybe play a role. The association between ABO blood groups and risk of thrombosis has been recognized for 6 many years. A number of studies have demonstrated that there were higher levels of Factor VIIIc (FVIII) and von Willebrand factor (vWF) in non-O blood groups than O blood group [18][19][20][21][22]. The elevated levels of the vWF-FVIII complex are associated with increased risk of venous thromboembolism [23]. Additionally, there is a longer prothrombin time (PT) in patients of obst ructive jaundice with O blood group than non-O blood group [24]. But in present study, there was not significant difference about PT in different ABO blood groups (table 3, shown in the supplemental data). Based on these studies, we speculated that lower warfarin dose requirements in patients with O blood group might be associated with high levels of FVIII and vWF.
A few limitations were apparent in present study. First, though warfarin dose requirements are higher in non-O blood groups than O blood group, the population of the study is small, especially in AB blood group, large sample would be needed to verify the relations between ABO blood groups and warfarin dose requirements. Secondly, it is a retrospective study, which made it that the effects of some genetic factors such as CYP2C9 and VKORC1 on warfarin dose requirements were not excluded [8][9][10]. Lastly, owing to the geographic distribution difference of ABO blood groups, the association between ABO blood groups and warfarin dose requirement in Chinese Han population from Chaoshan region may be different from other regions in China.

Conclusions
In summary, the present study demonstrated that patients with non-O blood groups

Acknowledgements
Not applicable.

Funding
None.

Availability of data and materials
Raw data supporting the obtained results are available at the corresponding author.

Authors' Contributions
SZ and LSW drafted the manuscript. ZLC, XHL and XRT were involved in data collection.
HJC performed the statistical analysis. MY conceived of the study. All authors read and approved the final manuscript.

Ethics approval and consent to participate
The study was approved by the ethics committee of Shantou University Medical College.
The need for consent was waived because of the retrospective data.

Consent for publication
Not applicable.  * O blood group vs A, B blood group P < 0.05