Factor VLeiden inhibits fibrinolysis in vivo.
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.


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.
Parker
Andrew C
AC
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0644, USA.
Mundada
Lakshmi V
LV
Schmaier
Alvin H
AH
Fay
William P
WP
D000818:Animals; D025901:Carboxypeptidase B2 / Q000037:antagonists & inhibitors; D005165:Factor V / Q000235:genetics*; D005342:Fibrinolysis / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D011655:Pulmonary Embolism / Q000097:blood; D013927:Thrombosis / Q000097:blood
C095381:factor V Leiden; D005165:Factor V; D025901:Carboxypeptidase B2