Plasma markers of coagulation and endothelial activation in Fabry disease: impact of renal impairment

Background. In Fabry disease, storage of globotriaosylceramide (Gb3) in arterial walls is one of the main pathogenetic factors that are thought to underlie the clinical manifestations of the disease. Abnormalities of the vessel wall, haemodynamics and pro- and anticoagulant factors may play a role, though the exact pathophysiology is incompletely understood. In this study, we try to clarify inconsistencies regarding coagulation activation, fibrinolysis, platelet activation and endothelial activation in 36 patients with Fabry disease. Methods. Cell-derived microparticles, markers for coagulation activation (F1+2, TAT, sTF, sEPCR), fibrinolysis (D-dimer, tPA, alpha(2)-AP), platelet activation (beta-TG, PF4), endothelial activation (vWF) and acute phase response (IL-6, CRP) were studied in relation to renal function and severity of the disease and compared to data from 36 age-and sex-matched healthy controls (17 males). Results. Markers for endothelial activation and fibrinolysis were normal. Male patients had elevated levels of sTF and beta-TG, with an association between sTF and renal function and severity of the disease. In female patients, levels of TAT, beta-TG, PF4, CD63-positive platelet-derived microparticles and IL-6 were somewhat increased, with no correlation with renal function or disease severity. Conclusions. Only minimal abnormalities in markers for platelet, endothelial activation and coagulation activation and fibrinolysis could be established in a large cohort of Fabry disease patients. The existing laboratory abnormalities are more likely related to renal insufficiency rather than to Fabry disease itself.