Bauer K A, Weiss L M, Sparrow D, Vokonas P S, Rosenberg R D
Charles A. Dana Research Institute, Boston, Massachusetts.
J Clin Invest. 1987 Dec;80(6):1527-34. doi: 10.1172/JCI113238.
In view of the known association of vascular disease with increasing age, we have conducted an analysis of hemostatic system activity with respect to perturbations induced by aging phenomena. We have utilized an immunochemical assay for prothrombin fragment F1 + 2 to quantify Factor Xa activity upon prothrombin in the plasma of 199 healthy males between the ages of 42 and 80. The levels of F1 + 2 in this population generally increased as a function of age (P less than 0.0001). The metabolic behavior of this marker was determined in 10 individuals greater than 65 yr of age with varying levels of F1 + 2, which ranged from 1.28 to 5.85 nM. The elevations in the concentration of this component were not due to diminished clearance of the fragment. Radio-immunoassays for fibrinopeptide A (FPA) and the protein C activation peptide (PCP) were subsequently employed to measure thrombin activity upon fibrinogen and thrombin-thrombomodulin activity upon protein C, respectively, in 82 members of this population ranging in age from 42 to 80. Significant positive correlations were again observed between increasing age and the level of F1 + 2 (P less than 0.0001) as well as FPA (P less than 0.01) and PCP (P less than 0.002). The results of this cross-sectional study indicate that many apparently normal males of increasing age with normal immunologic levels of antithrombin III and protein C exhibit a biochemical defect that denotes the presence of an acquired prethrombotic state.
鉴于血管疾病与年龄增长之间已知的关联，我们针对衰老现象引起的扰动，对止血系统活性进行了分析。我们利用免疫化学分析法检测凝血酶原片段F1 + 2，以量化199名年龄在42至80岁之间的健康男性血浆中凝血酶原上的因子Xa活性。该人群中F1 + 2的水平通常随年龄增长而升高（P小于0.0001）。在10名年龄大于65岁、F1 + 2水平各异（范围为1.28至5.85 nM）的个体中，测定了该标志物的代谢行为。该成分浓度的升高并非由于片段清除率降低所致。随后，我们采用纤维蛋白肽A（FPA）和蛋白C活化肽（PCP）的放射免疫分析法，分别测定了该人群中82名年龄在42至80岁之间的个体中纤维蛋白原上的凝血酶活性以及蛋白C上的凝血酶 - 血栓调节蛋白活性。年龄增长与F1 + 2水平（P小于0.0001）、FPA水平（P小于0.01）和PCP水平（P小于0.002）之间再次观察到显著的正相关。这项横断面研究的结果表明，许多年龄不断增长、抗凝血酶III和蛋白C免疫水平正常的明显健康男性表现出一种生化缺陷，这表明存在一种后天性血栓前状态。
