Effect of ABO Blood Groups, Age and Gender on Coagulation Assays in Patients With Acute Deep Vein Thrombosis

Background: Genetic polymorphisms, age, gender and body weight are major determinants of warfarin dose requirements. Our previous study showed that patients with non-O blood groups required higher doses of warfarin than those with O blood groups. However, the underling mechanism was not well known. Objectives: The study aimed to investigate the inuence of ABO blood group, age and gender on the values of coagulation tests in patients with acute deep vein thrombosis in Chinese Han population. Methods: A retrospective study was conducted in the First Aliated Hospital of Shantou University Medical College in Southern China. Two hundreds and 35 patients with conrmed diagnosis of acute deep vein thrombosis were included. Coagulation tests were determined. Results: Of 235 patients with acute deep vein thrombosis of lower extremities, 70 patients had blood group A (29.79%), 71 patients had blood group B (30.21%), 30 patients had blood group AB (12.77%), and 64 patients had blood group O (27.23%). The study showed no difference about coagulation tests among the patients with different blood groups. Coagulation tests were not affected by age and gender. Conclusion: Our study showed that ABO blood group, age and gender had no effects on coagulation tests in patients with acute deep vein thrombosis


Introduction
Deep vein thrombosis (DVT) is a major health problem worldwide, which can affect more than one out of 1000 people every year [1]. Endothelial injury, hypercoagulability and stasis are three main predisposing factors that favor thrombosis. The common risk factors for DVT included increasing age, obesity, previous venous thromboembolism, surgery, trauma and immobility [2].
ABO blood groups, an inherited characteristic, consist of four types: A, B, AB, and O blood group. The relations between ABO blood groups and human disorder have long been recognized. The potential roles of ABO blood groups in DVT have also been addressed. There is a higher risk for DVT in patients with non-O blood groups than in paients with blood group O [3][4][5]. More recently, we found that the patients in the O blood group had lower warfarin dose requirements than those in the A, B and AB blood groups [6].
However the underling mechanism was not well known.
The ABO blood type is long known to have a profound in uence on haemostasis, which was mainly associated with factor VIII and VIII levels [7,8]. It is notable that plasma vWF levels are approximately 25 30% lower in O type than non-O type individuals [9]. Therefore, ABO blood type likely affects coagulation assays such as activated partial thromboplastin time (APTT) and thrombin generation assay (TGA) values. It was reported that there is a higher APTT value in healthy volunteers with O blood group than that with non-O blood group [10,11]. Furthermore APTT were affected by age and sex [10].
Coagulation tests such as brinogen, brin degradation products and tissue plasrninogen activator antigen are higher in patients with DVT [12]. However the effects of ABO blood group, age and gender on coagulation tests in DVT remind to be determined. The present study is to investigate the in uence of ABO blood group, age and gender on the values of coagulation tests in patients with acute DVT. 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. P value < 0.05 was considered signi cant.

Results
As shown in the  Table 2). Considering the sample of group AB patients was small, we compared coagulation assays in blood group O and non-O patients. It was reported that the individuals with type O had prolonged APTT than those with type non-O [10,11]. However, as shown in Table S2, there was no difference about APTT between the patients with blood group O and non-O (no difference about the clinical characteristics of patients, shown in Table S3). APTT were signi cantly affected by age and sex, with lower APTT values in females than in males and negative correlation between age and APTT [10], but in present study signi cant effects of age (shown in Table

Discussion
Normal hemostasis is a state of ne balance between procoagulant and anticoagulant factors in circulating blood. DVT is a condition with blood clot developed in the veins. The standard treatment for patients with acute DVT is anticoagulant therapy. Though new oral anticoagulants such as dabigatran, rivaroxaban, apixaban and edoxaban are as safe and effective as vitamin K antagonists (VKAs) [13], warfarin is still the most widely-used anticoagulant in the world and remains a viable oral anticoagulant for many patients because of its availability and cost [14]. However, the anticoagulant activity of warfarin was affected by various factors, such as age, sex, body weight and genetic polymorphisms [15][16][17][18], it is not easy to maintain the target INR range. In previous study, we found that there is a higher dose of warfarin requirement in patients with non-O blood groups than O blood groups, the underling mechanism was not well known. Whether ABO blood type in uences coagulation assays in patients with acute DVT remain to be determind.
Coagulation tests are widely used in clinic to detect abnormalities of hemostasis. The PT, APTT, TT, INR and brinogen are commonly performed coagulation tests. The reference intervals had minor variation with sex and age in healthy individuals [19] while. Blood lipids in uence the values of PT but not APTT. Individuals with high triglyceride levels (≥ 200mg/dl) had shorter PT values than those with lower triglyceride levels [20]. APTT was signi cantly prolonged in healthy with type O than those with type non-O while PT was not affected [10,11]. A shorten APTT is associated with the risk of venous thromboembolism [21]. However, in the present study, there are no differences about APTT among the A, B, AB and O blood groups. Furthermore the difference about APTT between blood group O and non-O was not signi cant, which suggested that the effect of ABO blood group on APTT varied with race.
PT is used to evaluate the extrinsic and nal common pathways of coagulation, which is commonly used to monitor warfarin anticoagulant therapy. However, PT varied with the thromboplastin reagents and the instrument used in the laboratory, it is di cult to monitor warfarin anticoagulation and evaluate the anticoagulation effect of warfarin by PT. Fibrinogen plays a key role in the blood coagulation system. Elevated plasma brinogen level is a risk factor for cardiovascular disease [22,23]. Though brinogen was higher in patients with DVT than in controls [24], there were no signi cant differences in brinogen in patients with DVT for group O compared with group non-O blood group [25]. In the present study, no differences were also found in patients among A, B, AB and O blood group. Moreover the difference about APTT between blood group O and non-O was not signi cant, which con rmed the previous report [25].
Apart from ABO blood group, the effects of sex and age on APTT have also been reported [10], with a signi cant higher APTT value in males than in females and negative correlation with age. However there was no signi cant difference about the in uence of age and sex on APTT, suggesting the effect of age and sex on APTT also varied with race.
There were a few limitations in the present study. First, it was a retrospective study, unknown factors affecting coagulation tests can not be excluded. Second, the population of the study is small, large sample would be needed to verify the relations between APTT and ABO blood groups, sex and age in patients with acute DVT. Last, APTT varied with race [26], the association between ABO blood groups, sex, age and APTT in the Chinese Han population from the Chaoshan region may be different from that in populations from other races in China.
In summary, the present study demonstrated that coagulation tests were not affected by ABO blood group, age and gender in patients with acute deep vein thrombosis in the Chinese Han population from the Chaoshan region.

Declarations
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.

Availability of data and materials
Raw data supporting the obtained results are available at the corresponding author. Study pro le DVT, deep vein thrombosis;

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