Warfarin, an anticoagulant with vitamin K antagonist, is widely used for treatment of venous thromboembolism and prevention of stroke in patients with atrial fibrillation. Though effectiveness in preventing embolic strokes [15], maintain anticoagulation within the target INR range and preventing devastating risk of intracranial hemorrhage (ICH) remain challenging. To be effectiveness and safety, an INR target of 2.0-3.0 is widely adopted. Owing to the multitude of factors interacting with warfarin, it is not easy to maintain INR values within the target range of 2.0 to 3.0. To predict warfarin doses, Gage et al proposed a warfarin-dosing algorithm by combining cytochrome P450 2C9 (CYP2C9) 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 [12-14]. 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 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 [18-22]. 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 [8-10]. 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.