Published Online
on November 29, 2004

A more recent version of this article appeared on December 7, 2004

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Submitted on June 8, 2004
Revised on September 12, 2004
Accepted on September 24, 2004

Factor V^Leiden Inhibits Fibrinolysis In Vivo

Andrew C. Parker BS, Lakshmi V. Mundada MS, Alvin H. Schmaier MD, and William P. Fay MD^*

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

^* To whom correspondence should be addressed. E-mail: wfay{at}umich.edu.

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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Circulation 2004 110: 3503. [Full Text]

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