Abstract 18113: High Exercise-Induced Platelet Reactivity in Patients with Fabry Disease
Background: Cerebrovascular events represent a major cause of disability in young patients with Fabry disease (FD). However the pathogenesis of cerebrovascular events in these patients is not fully understood and prevention, besides enzyme replacement therapy (ERT), is empirically based on antiplatelet drugs. We evaluated platelet function in patients with FD without evidence of coronary or carotid atherosclerosis.
Methods: Fifteen patients with genetically confirmed FD (mean age 42, 6 F) underwent treadmill exercise stress test (EST). Platelet reactivity was assessed by flow cytometry at baseline and at peak EST, with and without ADP stimulation, by measuring monocyte-platelet aggregate (MPA) formation (expressed as percentage of monocyte binding platelets) and CD41 expression (assessed as mean fluorescence intensity). All patients underwent carotid ultrasound and coronary angiography to rule out carotid or coronary artery disease. Patients on ERT were submitted to EST the day before drug infusion. Thirty healthy sex- and age-matched subjects were studied as controls.
Results: Coronary angiography and carotid ultrasound showed no evidence of atherosclerosis in all FD patients; EST showed signs of ischemia in 3 patients with FD cardiomyopathy. Thirteen patients were on ERT at the time of the study. Compared to resting values, MPA and CD41 expression,with and without ADP stimulation, significantly increased after exercise in the FD group but not in controls. Exercise-induced values of MPA (20.1vs18.7, p=0.001 - with ADP:25.2vs22.0, p<0.0001) and CD41 expression (20.3vs19.4 p=0.006 - with ADP:26.1vs21.9, p<0.0001) were higher in FD patients than in controls, while resting values didn't significantly differ.
Conclusions: High exercise-induced platelet reactivity has been reported in patients at high risk for thrombotic events, like those with coronary or peripheral atherosclerosis. In this study we found high exercise-induced platelet reactivity in patients with FD, suggesting that enhanced platelet reactivity may contribute to the pathogenesis of cerebrovascular events in these patients. Our data support the inclusion of antiplatelet drugs in conventional therapy for FD. The effect of ERT on platelet function remains to be clarified.
- © 2011 by American Heart Association, Inc.