Factor V Leiden Inhibits Fibrinolysis In Vivo

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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; PfV+/Q mice (29.4±8.7%, n=9; PfVQ/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.