Thromboembolic events in Fabry disease and the impact of factor V Leiden

Objectives: Although several reports suggest an increased thromboembolic event rate, especially regarding strokes and TIAs at early age in patients with Fabry disease (FD), the risk for patients with FD to experience these events, the clinical relevance of additional risk factors including the concurrence of factor V Leiden (FVL), and the benefit of enzyme replacement therapy (ERT) regarding these events remain unclear.

Methods: Three hundred four consecutively recruited patients with FD were evaluated for their lifetime occurrence of thromboembolic events such as stroke, TIA, deep vein thrombosis, and pulmonary embolism. The thromboembolic risk was determined in patients with FD and concurrent FVL, and the impact of ERT was assessed.

Results: The 304 patients with FD had a median age of 41 years and 53 (17.4%) had experienced at least one thromboembolic event during their lifetime. Among 226 patients with FD screened for FVL, 16 gene carriers were identified (7.1%). The occurrence of thromboembolic events in patients with FD and concurrent FVL was significantly increased compared to those without FVL (hazard ratio = 5.45, 95% confidence interval 2.29–12.99; p < 0.001). Patients with FD receiving ERT had a significantly decreased risk of thromboembolic events compared to those without ERT (hazard ratio = 0.362, 95% confidence interval 0.132–0.992; p = 0.0422).

Conclusion: This observational study confirms that patients with FD have a high risk of clinically relevant thromboembolic events, which could be aggravated by a concurrence of FVL. ERT might be of benefit in preventing vascular events in patients with FD. The latter observation needs confirmation, however, by randomized and controlled clinical trials.