凝血因子V莱顿突变体在体内抑制纤维蛋白溶解。

Factor VLeiden inhibits fibrinolysis in vivo.

作者信息

Parker Andrew C, Mundada Lakshmi V, Schmaier Alvin H, Fay William P

机构信息

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0644, USA.

出版信息

Circulation. 2004 Dec 7;110(23):3594-8. doi: 10.1161/01.CIR.0000148781.87906.C0. Epub 2004 Nov 29.

DOI:10.1161/01.CIR.0000148781.87906.C0

PMID:15569834

Abstract

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.

摘要

背景

凝血因子V（莱顿）[fV（莱顿）]通过增强凝血酶形成而导致血栓形成倾向。本研究检验了fV（莱顿）在体内抑制纤维蛋白溶解的假说。

方法与结果

将放射性标记的血凝块注入野生型小鼠以及fV（莱顿）杂合子（fV（+/Q））或纯合子（fV（Q/Q））小鼠的颈静脉。5小时后，fV（Q/Q）小鼠的平均血凝块溶解百分比（14.3±3.6%，n = 13）与野生型小鼠（40.2±7.0%，n = 17；P<0.01）相比显著降低，fV（+/Q）小鼠处于中间水平（29.4±8.7%，n = 9；与fV（Q/Q）相比P<0.03，与野生型相比P = 0.36）。由fV（+/Q）或fV（Q/Q）小鼠制备的血浆凝块的体外溶解速率显著慢于野生型血浆凝块，而在抑制凝血酶激活的纤维蛋白溶解抑制剂后，各组之间的体外凝块溶解没有显著差异。