Factor VLeiden inhibits fibrinolysis in vivo

Abstract

Background - Factor VLeiden (fVLeiden) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fVLeiden inhibits fibrinolysis in vivo. Methods and Results - Radiolabeled clots were injected into the jugular veins of wild-type mice and mice heterozygous (fV+/Q) or homozygous (fVQ/Q) for fVLeiden. Mean percent clot lysis 5 hours later was significantly reduced in fVQ/Q mice (14.3±3.6%, n=13) compared with wild-type mice (40.2±7.0%, n=17; P<0.01) and intermediate in fV +/Q mice (29.4±8.7%, n=9; P<0.03 versus fVQ/Q, P=0.36 versus wild type). The rate of in vitro lysis of plasma clots prepared from fV+/Q or fVQ/Q mice was significantly slower than that of wild-type plasma clots, whereas in vitro clot lysis did not differ significantly between groups after inhibiting thrombin-activatable fibrinolysis inhibitor. Conclusions - fVLeiden inhibits fibrinolysis in vivo, suggesting an additional pathway by which this mutation promotes thrombosis.