Danish researchers have determined that ABO blood type, especially when combined with with certain genetic mutations, constitutes the most significant risk factor for formation of venous thromboembolism. The findings were published Feb. 4 in the Canadian Medical Association Journal.

Earlier studies had suggested that ABO antigen expression determined Willebrand factor levels, and other studies concluded that factor V Leiden R506Q and prothrombin G20210A are associated with increased risk of venous thrombosis. In the current study, Birgitte F. Sode, MD, PhD, of Herlev Hospital in Copenhagen, Denmark, and colleagues sought to assess whether ABO blood type, alone and in association with factor V Leiden R506Q and prothrombin G20210A, leads to increased risk of venous thromboembolism and MI in the general population.

Using two Danish registries of adults in the Copenhagen area from 1977 through 2010, the researchers determined the ABO genotypes, as well as the genotypes for the factor V Leiden R506Q and prothrombin G20210A mutations, of 66,001 individuals. Individuals with type O blood were classified as homozygous for polymorphism rs8176719, those with type B blood were classified as either homozygous for rs8176746 or heterozygous for rs8176719 and rs8176746. Participants with A blood had no polymorphism, and participants with AB were classified as heterozygous for rs8176746.

After adjusting for age, sex, current smoking, body mass index, systolic blood pressure and diabetes mellitus, the authors found the multivariable hazard ratio for venous thromboembolism was 1.4 among participants with non-O blood types compared to participants with type O blood. Heterozygous individuals with the factor V Leiden R506Q mutation had a hazard ratio of 2.2 compared with noncarriers of the mutation, and homozygous individuals with the mutation had a hazard ratio of 7 compared with noncarriers. Hazard ratios for heterozygous carriers of the prothrombin G20210A mutation was 1.5 and for homozygous carriers it was 11. There were stepwise increases in risk of venous thromboembolism when non-O blood type was combined with either of the mutations.

The researchers also investigated a link between MI incidence and blood type, the factor V Leiden R506Q and prothrombin G20210A mutations. They found no statistically significant associations.

Sode et al concluded that, “non-O blood type was the most important risk factor for venous thromboembolism, constituting 20 percent of the population attributable risk for venous thromboembolism, compared with 10 percent for factor V Leiden R506Q and 1 percent for prothrombin G20210A mutations. This suggests that ABO blood type should be included in genetic screening for thrombophilia.”

The authors acknowledged that their study population was entirely white, but pointed out that the genetic factors they studied are found universally and only vary by frequency among different ethnic groups. They urged caution in interpreting the results of the subgroup of individuals who were homozygous for factor V Leiden R506Q and prothrombin G20210A mutations, as this was a small population. As strengths, the authors cited the large size and extended duration of the study and the fact that follow-up was 100 percent complete.