España F, Vayá A, Mira Y, Medina P, Estellés A, Villa P, Falcó C, Aznar J
Research Center, La Fe University Hospital, Valencia, Spain.
Thromb Haemost. 2001 Dec;86(6):1368-73.
The levels of circulating activated protein C (APC) reflect in vivo protein C activation. The aim of this study was to determine whether a low APC level is an independent risk factor for venous thromboembolism (VTE). We measured APC in 160 patients with a history of VTE and without recognized thrombophilic defects, and in 199 healthy individuals. The mean (+/- SD) APC level was lower in patients (0.99 +/- 0.44 ng/ml) than in controls (1.19 +/- 0.41 ng/ml) (p < 0.0001), and showed a different distribution in the two groups. Thirty-eight patients (23.7%) had APC levels below the 5th percentile of the control group (<0.69 ng/ml) and 57 patients (35.6%) had APC levels below the 10th percentile (<0.77 ng/ml). APC levels <0.69 ng/ml increased the risk of a single or recurrent episode of VTE 4.2-fold (95% confidence interval, 2.0-9.0) or 6.9-fold (2.6-17.9). respectively, and APC levels <0.77 ng/ml increased these risks 3.4-fold (1.9-6.2) or 5.1-fold (2.3-11.2), respectively, compared with controls. Familial studies revealed that in some cases the low APC phenotype seems to be hereditary. We conclude that a low level of circulating APC in individuals without any of the most recognized thrombophilic defects is a prevalent, independent risk factor for VTE, and that it predisposes to recurrent VTE.
循环活化蛋白C（APC）水平反映体内蛋白C的活化情况。本研究旨在确定低APC水平是否为静脉血栓栓塞症（VTE）的独立危险因素。我们检测了160例有VTE病史且无公认血栓形成倾向缺陷的患者以及199名健康个体的APC水平。患者的平均（±标准差）APC水平（0.99±0.44 ng/ml）低于对照组（1.19±0.41 ng/ml）（p<0.0001），且两组的分布不同。38例患者（23.7%）的APC水平低于对照组的第5百分位数（<0.69 ng/ml），57例患者（35.6%）的APC水平低于第10百分位数（<0.77 ng/ml）。与对照组相比，APC水平<0.69 ng/ml使单次或复发性VTE发作的风险分别增加4.2倍（95%置信区间，2.0 - 9.0）或6.9倍（2.6 - 17.9），APC水平<0.77 ng/ml使这些风险分别增加3.4倍（1.9 - 6.2）或5.1倍（2.3 - 11.2）。家族研究表明，在某些情况下，低APC表型似乎具有遗传性。我们得出结论，在没有任何最公认的血栓形成倾向缺陷的个体中，循环APC水平低是VTE的一个普遍存在的独立危险因素，且易导致复发性VTE。
