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.
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.
Authors: E J Su; M Geyer; M Wahl; K Mann; D Ginsburg; H Brohmann; K U Petersen; D A Lawrence Journal: J Thromb Haemost Date: 2011-06 Impact factor: 5.824