Non-O Blood Type Is the Commonest Genetic Risk Factor for VTE: Results from a Meta-Analysis of the Literature

Abstract

It is well known that the ABO blood group exerts a major influence on hemostasis, as O blood group individuals have lower von Willebrand factor and factor VIII levels than non-O blood group subjects. To evaluate the possible clinical implication of the different ABO blood groups on the risk of developing venous thromboembolism (VTE), we conducted a meta-analysis of the existing literature. After an electronic search strategy using Medline and Embase and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, we included in the systematic review 38 studies with 10,305 VTE cases. The prevalence of non-O blood group was significantly higher in VTE patients compared with controls with a resulting pooled odds ratio (OR) of 2.09 (95% confidence interval [CI], 1.83, 2.38; p < 0.00001). Similar findings were obtained when the genotypes A1O/BO/A2B (OR 1.73, 95% CI, 1.47, 2.05; p < 0.00001) and A1B/A1A1/BB (OR 1.87, 95% CI, 1.84, 2.44; p < 0.00001) were analyzed. The maximum VTE risk was observed in non-O-factor V Leiden patients (OR 7.60, 95% CI, 3.21, 17.99), while for G20210A prothrombin mutation it was not possible to perform a pooled analysis due to a paucity of published studies. Finally, the association between non-O blood group and VTE was weaker when provoked VTE cases were considered (OR 1.33, 95% CI, 1.18, 1.50), while it was substantially unchanged when unprovoked VTE cases were analyzed (OR 1.88, 95% CI, 1.42, 2.50). In conclusion, considering its prevalence, non-O blood group is a candidate to be one of the most important genetic risk factors for venous thrombosis.

Relationship between ABO blood group and bleeding complications in orally anticoagulated patients

“…VTE vs. all other causes) the prevalence of non-O subjects was 73.9% (34/46) in the VTE group and 58.4% (80/137) in the non-VTE group, while the prevalence of blood group O subjects was 26.1% (12/ 46) in the VTE group and 41.6% (57/137) in the non-VTE group. Thus, if we exclude VTE patients, the ABO blood group distribution in this cohort of patients with bleeding complications during oral anticoagulant treatment is almost identical to that of the normal ABO blood group distribution in the healthy general population (data from all the 16 911 blood donors at Thus, the low prevalence of group O subjects and the high prevalence of subjects with non-O blood groups found in this cohort of subjects with anticoagulant-induced bleeding complications (37.7% and 62.3%, respectively) as compared with the prevalence in the healthy general population is clearly an artefact due to the inclusion in this cohort of cases with VTE, which has a well-known correlation with non-O blood group [2]. Another interesting finding of this study is the higher prevalence, albeit not statistically significant, of subjects with O blood group among the patients with grade 2 complications than among the patients with grade 1 complications (45.4% vs. 35.3%).…”

“…The effect of time between venipuncture, processing and freezing on the measurement of coagulation factor levels Coagulation factor levels are commonly measured in research studies evaluating the etiology of diseases, in particular vascular diseases. Levels within the upper 10% (> P90) of the population distribution of the procoagulant factors prothrombin, factor VIII, FIX, and FXI, and low levels of anticoagulation proteins, are associated with an increased risk of venous thrombosis [1][2][3][4][5]. Many preanalytic variables may affect the accuracy of these assays, including the duration of time from venipuncture to specimen processing and storage [6,7].…”

“…Relationship between ABO blood group and bleeding complications in orally anticoagulated patients While a number of studies have analysed the relationship between ABO blood group and vascular thrombosis [1], especially venous thromboembolism (VTE) [2], only a few data have been published on the association between ABO blood group and hemorrhagic disorders [3]. However, as plasma von Willebrand factor levels are 25-35% lower in subjects with type-O blood group than in non-O individuals [4], the question of whether the former subjects have an increased bleeding tendency is reasonable.…”

The utility of thrombophilia testing

“…Conversely, patients with Factor V Leiden often develop the first VTE episode after 45 years of age, most frequently in association with acquired (triggering) risk factors such trauma, surgery, pregnancy and oral contraceptives [13]. Among these well-established genetic factors, there is growing evidence that non-O blood group, which is associated with approximately 25% higher plasma von Willebrand factor and factor VIII levels (which are well-known thrombotic risk factors) than those in O blood type individuals, is associated with an approximately two-fold increased risk of VTE [14].…”

“…Conversely, patients with Factor V Leiden often develop the first VTE episode after 45 years of age, most frequently in association with acquired (triggering) risk factors such trauma, surgery, pregnancy and oral contraceptives [13]. Among these well-established genetic factors, there is growing evidence that non-O blood group, which is associated with approximately 25% higher plasma von Willebrand factor and factor VIII levels (which are well-known thrombotic risk factors) than those in O blood type individuals, is associated with an approximately two-fold increased risk of VTE [14].Clinical and epidemiological studies on prevalence of these thrombophilic traits, as well as on their association with development of VTE (Table 1), have led to defining the multifactorial nature of VTE, in which the thrombotic event is the result of multiple gene-gene and/ or gene-environment interactions. In keeping with this model, inherited thrombophilia interacts with several other well-established acquired predisposing factors for VTE such as age, malignancy, inflammatory states, antiphospholipid antibodies, surgery, trauma, immobility, pregnancy-puerperium, use of oral contraceptives or hormone replacement therapy, elevated body mass index, severe infections and venous abnormalities.…”