Clinical significance of factor V Leiden and prothrombin G20210A-mutations in cerebral venous thrombosis – comparison with arterial ischemic stroke

Abstract

Cerebrovascular diseases are considered in a different way concerning their etiology with regard to arterial and venous occlusion. The role of thrombophilia in this context remains undetermined. For this reason, a case-control study was conducted including a total of 202 patients (154 females, 48 males) aged from 18 to 76 years (mean: 39.8 years) suffering either from cerebral sinus venous thrombosis (n = 101) or from arterial ischemic stroke (n = 101). Study groups were evaluated on the basis of age- and gender-matched pairs. Gene mutations of factor V-1691 (factor V Leiden) and prothrombin-20210 being considered as the most common thrombophilia markers were analyzed in this study. Factor V Leiden-mutations were found in 16.8% of patients with cerebral sinus venous thrombosis (CVT) and in 17.8% of patients with arterial ischemic stroke (AIS), which was significantly more frequent than in controls at a rate of 4.95% (ORs: 3.89 and 4.16). Prothrombin-mutations were significantly more frequent in CVT at a rate of 14.9% versus 2.97% in controls (OR: 5.70). This does not apply for AIS showing a rate of 4.95% prothrombin-mutations. Rates of factor V Leiden-mutations are not different in CVT compared with AIS. In contrast, however, prothrombin-mutations were significantly more frequent in CVT than in AIS with a rate of 14.9% versus 4.95% (OR 3.35). Furthermore, 3 cases with combined heterozygosity of factor V Leiden- and prothrombin-mutation have been identified in CVT, but not in AIS or controls. All of the above mentioned mutations were exclusively heterozygous. We conclude from these data that thrombophilia in terms of factor V Leiden genotype is a risk factor for both CVT and AIS in equal measure. In contrast, prothrombin-20210-mutations were different playing a significant role in the pathogenesis of cerebral sinus vein thrombosis, but not in arterial ischemic stroke. Also, the combined occurrence of heterozygous prothrombin- and factor V Leiden-mutation clearly favors the emergence of cerebral sinus venous thrombosis. Therefore, in terms of thrombophilia such as investigated in this study, pathogenesis of arterial and venous occlusions in cerebrovascular disease has to be regarded as different.