Enhanced thrombin generation potential in male and female patients with Fabry disease: a single-center observational study

Fabry disease (FD) is an ultrarare X-linked lysosomal storage disorder, resulting in the generalized cell accumulation of glycosphingolipids. Patients with FD are at increased risk of thromboembolic events. In 34 clinically stable FD patients ( n = 17 [50%] men) and 34 controls matched by age, sex, and body mass index, we assessed the thrombin generation profile in plasma, using the calibrated automated thrombogram, in relation to clinical disease characteristics and laboratory parameters. FD patients were characterized by a 17.6% increase in endogenous thrombin potential (ETP) and a 9.8% higher thrombin peak ( p = 0.009 and p = 0.008, respectively) compared to controls. They also had significantly elevated platelet counts (by 20.1%), factor VIII activity (by 50.6%), and fibrinogen levels (by 20.0%). A multiple regression model revealed that higher ETP in FD was independently determined by increased platelet counts, C-reactive protein, and fibrinogen, accounting for 39% of ETP variability. Comparison with controls of the same sex showed increased thrombin generation parameters only in FD men. In conclusion, FD patients exhibit an unfavorable altered thrombin generation profile, suggesting an increased risk of thrombosis. Further prospective studies are needed to determine whether enhanced thrombin generation can predict cardiovascular events in this population.