van Hylckama Vlieg A, van der Linden I K, Bertina R M, Rosendaal F R
Department of Clinical Epidemiology and Hemostasis and Thrombosis Research Center, Leiden University Medical Center, Leiden, The Netherlands.
Blood. 2000 Jun 15;95(12):3678-82.
Elevated plasma levels of factor VIII (> 150 IU/dL) are an important risk factor for deep vein thrombosis (DVT). Factor VIII is the cofactor of factor IXa in the activation of factor X. The risk of thrombosis in individuals with an elevated factor IX level is unknown. This study investigated the role of elevated factor IX levels in the development of DVT. We compared 426 patients with a first objectively diagnosed episode of DVT with 473 population controls. This study was part of a large population-based case-control study on risk factors for venous thrombosis, the Leiden Thrombophilia Study (LETS). Using the 90th percentile measured in control subjects (P(90) = 129 U/dL) as a cutoff point for factor IX levels, we found a 2- to 3-fold increased risk for individuals who have factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by adjustment for possible confounders (age, sex, oral contraceptive use, and high levels of factor VIII, XI, and vitamin K-dependent proteins). After exclusion of individuals with known genetic disorders, we still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of premenopausal women not using oral contraceptives (OR: 12.4, CI: 3.3-47.2). These results show that an elevated level of factor IX is a common risk factor for DVT. (Blood. 2000;95:3678-3682)
血浆中凝血因子VIII水平升高（>150 IU/dL）是深静脉血栓形成（DVT）的重要危险因素。凝血因子VIII是激活因子X过程中因子IXa的辅因子。凝血因子IX水平升高的个体发生血栓形成的风险尚不清楚。本研究调查了凝血因子IX水平升高在DVT发生中的作用。我们将426例首次经客观诊断为DVT发作的患者与473名人群对照进行了比较。本研究是一项基于人群的大型静脉血栓形成危险因素病例对照研究——莱顿血栓形成倾向研究（LETS）的一部分。以对照组中测得的第90百分位数（P(90)=129 U/dL）作为凝血因子IX水平的截断点，我们发现凝血因子IX水平高于129 U/dL的个体与低于该截断点的个体相比，风险增加了2至3倍。该风险不受对可能混杂因素（年龄、性别、口服避孕药使用情况以及凝血因子VIII、XI和维生素K依赖蛋白水平升高）进行校正的影响。在排除已知遗传性疾病的个体后，我们仍发现比值比（OR）为2.5（95%置信区间[CI]：1.6 - 3.9）。女性的风险（OR：2.6，CI：1.6 - 4.3）高于男性（OR：1.9，CI：1.0 - 3.6），且在未使用口服避孕药的绝经前女性组中似乎最高（OR：12.4，CI：3.3 - 47.2）。这些结果表明，凝血因子IX水平升高是DVT的常见危险因素。（《血液》。2000年；95：3678 - 3682）
