Elevated plasma gas6 levels are associated with venous thromboembolic disease
Elevated plasma gas6 levels are associated with venous thromboembolic disease
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DOI：
10.1007/s11239-011-0597-2
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Kahn, Susan R.
中科院分区：
文献类型：
--
作者：
Blostein, Mark D.;Rajotte, Isabelle;Kahn, Susan R.
生长抑制特异性6（gas 6），一种新的维生素K依赖性蛋白，已被证明具有血栓稳定的作用，因为gas 6 null小鼠对致命的静脉和动脉血栓形成具有抗性。然而，气体6和静脉血栓栓塞之间的关联尚未阐明在人类。本研究旨在评估气体6在人类静脉血栓栓塞（VTE）疾病中的作用。使用高度特异性的ELISA方法，我们测量了279例静脉血栓栓塞症患者和79名健康志愿者的血浆样本中的gas 6水平。记录用药史、合并症和VTE特征。与健康志愿者相比，VTE患者的平均gas 6水平较高，分别为46 +/- 11 ng/ml和35 +/- 6.4 ng/ml（P < 0.001）。在整个研究人群中，通过回归模型估计了气体6水平升高（健康志愿者的千分之九十百分位数）时VTE的比值比（OR）。在调整年龄、性别、药物和合并症后，与气体水平较低的受试者相比，气体水平升高的受试者6发生VTE的风险增加（OR为16.3（95% CI 5.8-45.7，P < 0.001））。即使在年龄分布相当的患者中，这种关联也仍然显著。在静脉血栓栓塞患者中，平均气体水平在血栓更广泛的患者中显示出更高的趋势。Gas 6水平升高与VTE复发无相关性。总之，我们证明了静脉血栓栓塞和升高的气体6水平之间的关联与体内小鼠血栓形成模型一致。这构成了人类血栓形成的潜在新机制，并可能有助于理解VTE的病理生理学。
Growth arrest-specific 6 (gas6), a novel vitamin K-dependent protein, has been demonstrated to have a role in thrombus stabilization as gas6 null mice are resistant to lethal venous and arterial thrombosis. However, the association between gas6 and venous thromboembolism has not been elucidated in humans. The present study aims to assess the role of gas6 in human venous thromboembolic (VTE) disease. Using a highly specific ELISA method, we measured plasma levels of gas6 in plasma samples obtained from 279 patients with VTE and 79 healthy volunteers. Medication history, comorbid conditions and VTE characteristics were documented. Mean gas6 levels were higher in patients with VTE as compared to healthy volunteers, being 46 +/- 11 ng/ml and 35 +/- 6.4 ng/ml respectively (P < 0.001). Odds ratios (OR) for VTE given elevated (a parts per thousand yen90th percentile of healthy volunteers) gas6 levels were estimated in regression models in the whole study population. After adjustment for age, sex, medications and comorbidity, subjects with elevated gas6 had an increased risk of VTE (OR of 16.3 (95% CI 5.8-45.7, P < 0.001) compared to those with lower levels of gas6. This association remains significant even among patients with a comparable age distribution. Among patients with VTE, mean gas levels showed a trend of higher levels in those with more extensive thrombi. There was no correlation between elevated gas6 levels and recurrent VTE. In conclusion, we demonstrate an association between VTE and elevated gas6 levels consistent with in vivo murine models of thrombosis. This constitutes a potential novel mechanism for thrombosis in humans and may aid in the understanding of the pathophysiology of VTE.