Mari Daniela, Coppola Raffaella, Provenzano Rita
Department of Medical Sciences, IRCCS Istituto Auxologico Italiano, University of Milan, Italy.
Exp Gerontol. 2008 Feb;43(2):66-73. doi: 10.1016/j.exger.2007.06.014. Epub 2007 Jul 4.
With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. Centenarians had striking signs of heightened coagulation enzyme activity, accompanied by signs of enhanced formation of fibrin and secondary hyperfibrinolysis. Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. It is of interest that centenarians have a significantly higher frequency than young individuals of the high risk 4G allele of the PAI-1-675 (4G/5G) polymorphism, mutant factor V (Arg506Gln) and prothrombin gene G20210A mutation. Von Willebrand factor (VWF), a well-known independent predictor of atherothrombotic disease, was increased in centenarians, independently of the blood group, confirming the previous results of a state of hypercoagulability. The finding that the VWF cleaving proteases levels are low when VWF levels are high in centenarians could be a corollary of the previous described paradox of successful aging, adding another marker of increased risk of atherothrombosis to the scenario. Alike, high prevalence of anti-phospholipids antibodies, not associated with an anti-phospholipid syndrome has been described in centenarians. In conclusion, the data show the oldest old do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis.
随着年龄的增长,越来越多的健康个体出现凝血酶活性升高的实验室指标。这种生化高凝状态可能是年龄增长导致血栓形成倾向增加的基础,也可能是该过程的一种无害表现。百岁老人有明显的凝血酶活性升高迹象,同时伴有纤维蛋白形成增加和继发性纤溶亢进的迹象。百岁老人血浆纤维蛋白原和凝血因子VIII浓度高于对照组,而其他凝血因子并未升高。有趣的是,百岁老人中PAI - 1 - 675(4G/5G)多态性的高风险4G等位基因、突变型凝血因子V(Arg506Gln)和凝血酶原基因G20210A突变的频率显著高于年轻人。血管性血友病因子(VWF)是动脉粥样硬化血栓形成疾病的一个著名独立预测因子,在百岁老人中升高,且与血型无关,证实了先前高凝状态的结果。百岁老人中VWF水平高时VWF裂解蛋白酶水平低这一发现可能是先前所述成功衰老悖论的必然结果,为这一情况增加了另一个动脉粥样硬化血栓形成风险增加的标志物。同样,在百岁老人中也发现了与抗磷脂综合征无关的抗磷脂抗体高患病率。总之,数据表明最长寿的老年人也未能逃脱与衰老相关的高凝状态,但这种现象与健康和长寿是相容的。因此,老年人群中凝血激活标志物的高血浆水平不一定反映动脉或静脉血栓形成的高风险。