α-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation

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Abstract
Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue fibrin deposition in mice carrying combined mutations in FvL and Gla . Gla deficiency markedly increased tissue fibrin deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P Conclusions— These observations demonstrate a synergistic interaction between Gla deficiency and FvL toward tissue fibrin deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.