Haemostatic genetic variants, ABO blood group and bleeding risk during oral anticoagulant treatment after cerebral ischaemia of arterial origin.
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.
Pruissen
D M O
DM
Dept. of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
Rosendaal
F R
FR
Gorter
J W
JW
Garcia
A A
AA
Kappelle
L J
LJ
Algra
A
A
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
D000017:ABO Blood-Group System; D000925:Anticoagulants; D001798:Blood Proteins; C464794:fibrinogen Aalpha; D013912:Threonine; D005340:Fibrinogen; D000409:Alanine