Haemostatic genetic variants, ABO blood group and bleeding risk during oral anticoagulant treatment after cerebral ischaemia of arterial origin

Abstract

Oral anticoagulant treatment for secondary prevention after cerebral ischaemia of presumed arterial origin is associated with a higher bleeding rate than cardioembolic stroke. This discrepancy is only partly explained by known bleeding risk factors. Haemostatic genetic variants and AB0 blood group may be involved. We performed a nested casecontrol study in patients with cerebral ischaemia of presumed arterial origin on anticoagulant treatment (International Normalized Ratio between 3.0-4.5). All 34 cases with non-fatal haemorrhage (10 intracranial and 24 extracranial) and 68 control patients on anticoagulant treatment without such a bleeding were selected from the SPIRIT study. AB0 blood group and 11 haemostatic genetic variants were investigated. The Thr312Ala variant of the alpha fibrinogen gene was associated with a decreased bleeding risk (odds ratio (OR) 0.3 for Ala/Ala and Thr/Ala versus Thr/Thr genotype; 95% CI 0.1-0.8). Factor V Leiden was associated with an increased bleeding risk (OR 11.6; 95% CI 1.3-103). The APOE2 allele (OR 0.5; 95% CI 0.2-1.7) and the Tyr204Phe variant in the factor XIII subunit A (OR 2.1; 0.9-5) had nonsignificant relationships with bleeding risk. AB0 blood group and 7 other genetic variants in coagulation factors II and XIII, vitamin K epoxide reductase complex, beta fibrinogen and apolipoprotein E were not related with the risk of haemorrhage. The Ala312Thr variant in the alpha fibrinogen gene is associated with a decreased and factor V Leiden with an increased bleeding risk in patients on anticoagulant treatment after cerebral ischaemia of presumed arterial origin.

Relationship between ABO Blood Group and Hemorrhage: A Systematic Literature Review and Meta-Analysis

“…Other investigators analyzed the relationship between ABO blood group and bleeding risk in patients with concomitant risk factors for hemorrhage, such as the treatment with vitamin K antagonists (VKA). 18,19 A Dutch study that analyzed ABO blood group genotypes using data from the FACTors in ORal anticoagulation Safety (FACTORS) case-control study showed that the risk for nonfatal major bleeding in non-OO blood group carriers was 30% lower than that of OO blood group carriers, although the difference was not statistically significant (OR ¼ 0.7; 95% CI ¼ 0.4 to 1.1). 18 By contrast, Pruissen and colleagues, 19 analyzing 651 patients receiving oral anticoagulant treatment included in the Stroke Prevention in Reversible Ischemia Trial, found that ABO blood group was not related with the risk of hemorrhage during oral anticoagulant treatment after cerebral ischemia.…”

“…Furthermore, as assessment of methodologic quality, we decided to consider higher quality studies in which investigators did not use population data as controls. [13][14][15][16][17][18][19][20][21][22][23]…”

“…Therefore, 22 studies were finally included in our systematic review. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][33][34][35][36]…”

“…Baseline characteristics of included studies are summarized in ►Table 2. All included studies provided data on the prevalence of blood groups in patients with bleeding events and in controls: cases included patients with upper gastrointestinal bleeding (12 studies [13][14][15][16][17]24,[26][27][28]30,33,34,36 ), patients with cerebral hemorrhage (2 studies 34,35 ), patients with intra-or postpartum hemorrhage (1 study 20 ), patients with mucouscutaneous hemorrhage (2 studies 23,29 ), patients with epistaxis (1 study 22 ), patients with menorrhagia (1 study 25 ), patients with bleeding during anticoagulant treatment (2 studies 18,19 ), and patients with general bleeding problems (1 study 21 ). For 9 studies, a subgroup of patients included in the original study was selected for the aim of our systematic review.…”

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

“…A Dutch study, which analysed ABO blood group genotypes using data from the FACTors in ORal anticoagulation Safety (FACTORS) case-control study, showed that the risk of non-fatal major bleeding in non-OO blood group carriers was 30% lower than that in OO blood group carriers, although the difference was not statistically significant (OR, 0.7; 95% CI, 0.4-1.1) [13]. Subsequently, Pruissen et al [14], analysing 651 patients receiving oral anticoagulant treatment included in the Stroke Prevention In Reversible Ischemia Trial (SPIRIT), found that ABO blood group was not related to the risk of hemorrhage during oral anticoagulant treatment after cerebral ischemia.…”