title: 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.
authors.affiliation: Dept. of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
authors.forename: D M O
authors.initials: DM
authors.lastname: Pruissen
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: J W
authors.initials: JW
authors.lastname: Gorter
authors.forename: A A
authors.initials: AA
authors.lastname: Garcia
authors.forename: L J
authors.initials: LJ
authors.lastname: Kappelle
authors.forename: A
authors.initials: A
authors.lastname: Algra
mesh_terms: D000017:ABO Blood-Group System; D000284:Administration, Oral; D000368:Aged; D000409:Alanine / Q000235:genetics; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001158:Arteries / Q000473:pathology*; D001798:Blood Proteins / Q000235:genetics*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D013912:Threonine / Q000235:genetics
chemical_list: D000017:ABO Blood-Group System; D000925:Anticoagulants; D001798:Blood Proteins; C464794:fibrinogen Aalpha; D013912:Threonine; D005340:Fibrinogen; D000409:Alanine