Thrombosis in inflammatory bowel diseases: role of inherited thrombophilia

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by an increased risk for venous and arterial thrombosis. Although the pathogenetic mechanisms of this predisposition are unclear, a possible role of inherited risk factors for thrombosis in determining this predisposition has been suggested. AIM: To evaluate the role of factor V Leiden (G1691A) and G20210A prothrombin gene mutations in determining the occurrence of thrombosis in IBD patients. PATIENTS AND METHODS Forty-seven IBD patients (30 ulcerative colitis and 17 Crohn's disease) with a positive history for thrombosis (9 at arterial sites and 38 at venous sites) were enrolled in the study. For each patient, two non-IBD subjects matched for sex and age, type, and site of thrombosis were used as controls. Peripheral blood DNA specimens were amplified by PCR using appropriate primers and analyzed by restriction analysis on agarose gel electrophoresis. Statistical analysis was performed by means of Fisher's exact test. RESULTS: The total number of subjects with one or both mutations was significantly lower in IBD patients with thrombosis than in control subjects (12.8% vs 29.8%, respectively; p = 0.035, OR = 0.34, 95% CI 0.13-0.90). The total frequency of the mutated alleles was also significantly lower in IBD than in controls (7.4% vs 16.5%, respectively; p = 0.041, OR = 0.40, 95% Cl 0.17-0.96). Prothrombotic mutations were particularly unfrequent in IBD patients with active disease at the time of thrombosis compared with patients with quiescent disease (8.0% vs 36.4%, respectively; p = 0.057, OR = 0.15, 95% CI 0.02-1.01). CONCLUSIONS: The major inherited risk factors for thrombosis are significantly less frequent in thrombotic IBD patients than in thrombotic non-IBD subjects, suggesting that acquired risk factors play the most relevant role in determining thromboembolic events observed in IBD patients, particularly during active phases of the disease