Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients

Abstract

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.

Testing for Inherited Thrombophilias in Arterial Stroke

“…We would consider ordering a thrombophilic work-up in patients with a positive family or personal history of VTE, especially if unprovoked, or if other clinical features suggest paradoxical embolism. The decision 21 18-50 67 cryptogenic stroke 2 of 20 subjects (10%) were PFO(ϩ) and FVL(ϩ); 7 of the remaining 126 PFO(Ϫ) subjects (6%) were FVL(ϩ); this was not statistically significant Ϫ19 had PFO(ϩ) 79 noncryptogenic stroke Ϫ1 had PFO(ϩ) Nabavi (1998) 24 14-45 225 TIA or ischemic stroke 36% of cases were PFO(ϩ); 53% (8/15) FVL(ϩ) cases were also PFO(ϩ), whereas 35% (66/190) of FVL(Ϫ) cases were PFO(ϩ), Pϭ0.15 Ϫ205 were evaluated for PFO 200 healthy white subjects ASA indicates atrial septal aneurysm; AT, antithrombin deficiency; FVL, factor V Leiden; PC, protein C deficiency; PFO, patent foramen ovale; PS, protein S deficiency; PTM, prothrombin gene mutation; (ϩ), present; (Ϫ), absent. *Abstract only.…”

“…Nabavi et al 24 examined the prevalence of FVL in young stroke survivors by review of medical records and stroke data banks. Whereas the overall difference between cases and controls was not significant, the FVL mutation occurred in significantly more cryptogenic stroke patients.…”

“…Without limitation to the number of subjects, we identified 9 case-control studies examining the relationship of the inherited thrombophilias, patent foramen ovale (PFO), and stroke 21,24,[37][38][39][40][41][42][43] (Table 3). Sastry et al 9 collected data on both PFO and thrombophilia in ischemic stroke but did not evaluate them in relation to each other.…”

“…Sastry et al 9 collected data on both PFO and thrombophilia in ischemic stroke but did not evaluate them in relation to each other. These studies also produced conflicting results, with some studies suggesting an association between PTM or FVL and PFO, 24,[41][42][43] and others finding no relation. 21,[37][38][39][40] None of the studies that examined PC, PS, or AT found any association of these deficiencies with PFO and stroke.…”

Inherited Thrombophilia in Ischemic Stroke and Its Pathogenic Subtypes

“…[1][2][3] These conditions, the thrombophilias, include deficiencies of the natural anticoagulants such as antithrombin III, 4,5 protein S, 6,7 and protein C; 8 -12 and single point mutations in coagulation molecules such as factor V Leiden (1691G/A) [13][14][15][16] ; or the 3Ј untranslated region of the prothrombin gene (factor II) (20210 G/A). 17,18 There is little doubt that inherited thrombophilias can cause venous thrombosis, but most individuals with a single genetic risk factor will not have a thrombotic event in the absence of circumstantial risk factors such as immobility or the oral contraceptive pill.…”