Polymorphisms of clotting factors modify the risk for primary intracranialhemorrhage

Intracranial hemorrhage is the third most frequent cause of cerebrovascular disease, but few genetic risk factors have been associated with its develo pment. Recently, it has been reported that some polymorphisms that affect c lotting factors increase the risk for thrombosis. However, reports have ana lyzed the effect of polymorphisms influencing the hemostatic state in bleed ing disorders insufficiently. A case-control study was conducted of 201 pat ients with spontaneous intracranial hemorrhage and 201 control subjects mat ched for age, race, sex, and selected risk factors (hypertension, smoking, and alcohol consumption). Genomic polymerase chain reaction was used to ana lyze the prevalence of 4 polymorphisms: factor V Leiden, prothrombin 20210A , factor VII-323 Del/Ins of a decanucleotide, and factor XIII V34L. Subject s with factor V Leiden had decreased risk for spontaneous intracranial hemo rrhage (odds ratio, 0.19; 95% confidence interval, 0.03-0.95). The frequenc y of the prothrombin 20210A/G genotype was also lower among patients than c ontrols (1.5% vs 3%, respectively). Moreover, carriers of the -323 Ins alle le of factor VII had a 1.54-fold risk for intracranial hemorrhage (95% Cl, 1.03-2.72). Finally, no significant differences were observed in the preval ence of factor XIII V34L polymorphism between patients and controls. Theref ore, new genetic factors affecting the risk for spontaneous intracranial he morrhage were identified. These data, together with the relevance of these polymorphisms in thrombotic diseases, support the idea that a polymorphism may play opposite roles in thrombosis and hemorrhage, suggesting an explana tion for the high frequency of these polymorphisms in the general populatio n. (Blood. 2001;97-.2979-2982) (C) 2001 by The American Society of Hematolo gy.