Santamaría A, Oliver A, Borrell M, Mateo J, Belvis R, Martí-Fábregas J, Ortín R, Tirado I, Souto J C, Fontcuberta J
Department of Hematology, Hospital de la Santa Creu i Sant Pau, C/ Sant Antoni Ma Claret, 167, 08025-Barcelona, Spain.
Stroke. 2003 Oct;34(10):2387-91. doi: 10.1161/01.STR.0000088642.07691.15. Epub 2003 Aug 28.
Recently, a novel procarboxypeptidase B-like proenzyme, called thrombin-activatable fibrinolysis inhibitor (TAFI), has been described. It plays an important role in the delicate balance between coagulation and fibrinolysis. TAFI leads to potent inhibition of tissue plasminogen activator-induced fibrinolysis. The relevance of TAFI in thromboembolic disease is unclear. We have investigated the risk of ischemic stroke (IS) in relation to plasma levels of functional TAFI.
In a case-control study, we enrolled 264 individuals; 114 had IS, and 150 were recruited as controls who were age and sex matched and had no history of arterial disease. The individuals supplied information on their personal and family histories of cardiovascular diseases and conventional cardiovascular risk factors. Functional TAFI assays were performed by use of a method based on the activation of TAFI with thrombin-thrombomodulin and the measure of the TAFI activity generated. Other hemostatic parameters assayed were factor VIIIc, anti-phospholipid antibodies,fibrinogen, factor V Leiden, and the prothrombin gene G20210A mutations (PT20210A).
Functional TAFI levels were significantly higher in patients with IS (113.7+/-25%; range, 57% to 209%) than in controls (102.6+/-19%). The odds ratio for IS in patients with functional TAFI levels >120% was 5.7 (95% confidence interval, 2.3 to 14.1).
We found that functional TAFI levels in plasma (>120%) increased the risk of IS approximately 6-fold. Further studies should elucidate the physiological role of TAFI in arterial disease and possibly provide clues to therapeutic approaches.
最近，一种新型的类羧肽酶B原酶，即凝血酶激活的纤溶抑制物（TAFI）已被描述。它在凝血与纤溶之间的微妙平衡中起重要作用。TAFI可有效抑制组织型纤溶酶原激活物诱导的纤溶。TAFI在血栓栓塞性疾病中的相关性尚不清楚。我们研究了功能性TAFI血浆水平与缺血性卒中（IS）风险的关系。
在一项病例对照研究中，我们纳入了264名个体；114例患有IS，150例被招募为对照，他们在年龄和性别上相匹配且无动脉疾病史。这些个体提供了关于其个人和家族心血管疾病史以及传统心血管危险因素的信息。功能性TAFI检测采用基于凝血酶 - 血栓调节蛋白激活TAFI并测量产生的TAFI活性的方法进行。检测的其他止血参数包括因子VIIIc、抗磷脂抗体、纤维蛋白原、因子V Leiden和凝血酶原基因G20210A突变（PT20210A）。
IS患者的功能性TAFI水平（113.7±25%；范围为57%至209%）显著高于对照组（102.6±19%）。功能性TAFI水平>120%的患者发生IS的比值比为5.7（95%置信区间，2.3至14.1）。
我们发现血浆中功能性TAFI水平（>120%）使IS风险增加约6倍。进一步的研究应阐明TAFI在动脉疾病中的生理作用，并可能为治疗方法提供线索。
