Polymorphisms of clotting factors modify the risk for primary intracranial hemorrhage.

Intracranial hemorrhage is the third most frequent cause of cerebrovascular disease, but few genetic risk factors have been associated with its development. Recently, it has been reported that some polymorphisms that affect clotting factors increase the risk for thrombosis. However, reports have analyzed the effect of polymorphisms influencing the hemostatic state in bleeding disorders insufficiently. A case-control study was conducted of 201 patients with spontaneous intracranial hemorrhage and 201 control subjects matched for age, race, sex, and selected risk factors (hypertension, smoking, and alcohol consumption). Genomic polymerase chain reaction was used to analyze the prevalence of 4 polymorphisms: factor V Leiden, prothrombin 20210A, factor VII-323 Del/Ins of a decanucleotide, and factor XIII V34L. Subjects with factor V Leiden had decreased risk for spontaneous intracranial hemorrhage (odds ratio, 0.19; 95% confidence interval, 0.03-0.95). The frequency of the prothrombin 20210A/G genotype was also lower among patients than controls (1.5% vs 3%, respectively). Moreover, carriers of the -323 Ins allele of factor VII had a 1.54-fold risk for intracranial hemorrhage (95% CI, 1.03-2.72). Finally, no significant differences were observed in the prevalence of factor XIII V34L polymorphism between patients and controls. Therefore, new genetic factors affecting the risk for spontaneous intracranial hemorrhage 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 explanation for the high frequency of these polymorphisms in the general population.