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(Circulation. 2004;110:3594-3598.)
© 2004 American Heart Association, Inc.

Vascular Medicine

Factor V^Leiden Inhibits Fibrinolysis In Vivo

From the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.

Correspondence to William Fay, MD, University of Michigan, 7301 MSRB III, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0644. E-mail wfay{at}umich.edu

Received June 8, 2004; revision received September 12, 2004; accepted September 24, 2004.

Background— Factor V^Leiden (fV^Leiden) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV^Leiden 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 (fV^Q/Q) for fV^Leiden. Mean percent clot lysis 5 hours later was significantly reduced in fV^Q/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 fV^Q/Q, P=0.36 versus wild type). The rate of in vitro lysis of plasma clots prepared from fV^+/Q or fV^Q/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— fV^Leiden inhibits fibrinolysis in vivo, suggesting an additional pathway by which this mutation promotes thrombosis.

Key Words: fibrin • fibrinolysis • coagulation • thrombosis • thrombolysis

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