Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Blood. 2010 Jan 14;115(2):388-95. doi: 10.1182/blood-2009-03-211557. Epub 2009 Nov 18.
In Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic veins or inferior vena cava. To study the relationship between hypofibrinolysis and BCS, we measured plasma levels of fibrinolysis proteins in 101 BCS patients and 101 healthy controls and performed a plasma-based clot lysis assay. In BCS patients, plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in controls (median, 6.3 vs 1.4 IU/mL, P < .001). Thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor levels were lower than in controls (13.8 vs 16.9 microg/mL and 0.91 vs 1.02 U/L, both P < .001). Median plasma clot lysis time (CLT) was 73.9 minutes in cases and 73.0 minutes in controls (P = .329). A subgroup of cases displayed clearly elevated CLTs. A CLT above the 90th or 95th percentile of controls was associated with an increased risk of BCS, with odds ratios of 2.4 (95% confidence interval, 1.1-5.5) and 3.4 (95% confidence interval, 1.2-9.7), respectively. In controls, only PAI-1 activity was significantly associated with CLT. Analysis of single nucleotide polymorphisms of fibrinolysis proteins revealed no significant differences between cases and controls. This case-control study provides the first evidence that an impaired fibrinolytic potential, at least partially caused by elevated PAI-1 levels, is related to the presence of BCS.
在 Budd-Chiari 综合征 (BCS) 中,肝静脉或下腔静脉发生血栓形成。为了研究纤溶活性降低与 BCS 的关系,我们测量了 101 例 BCS 患者和 101 例健康对照者的血浆纤溶蛋白水平,并进行了基于血浆的血栓溶解测定。在 BCS 患者中,纤溶酶原激活物抑制剂 1(PAI-1)水平明显高于对照组(中位数分别为 6.3 和 1.4IU/mL,P <.001)。凝血酶激活的纤溶抑制物和纤溶抑制剂水平低于对照组(分别为 13.8 和 16.9μg/mL 和 0.91 和 1.02U/L,均 P <.001)。病例组的中位血浆血栓溶解时间(CLT)为 73.9 分钟,对照组为 73.0 分钟(P =.329)。病例组中有一部分 CLT 明显升高。CLT 高于对照组第 90 或 95 百分位数与 BCS 的风险增加相关,优势比分别为 2.4(95%置信区间,1.1-5.5)和 3.4(95%置信区间,1.2-9.7)。在对照组中,仅 PAI-1 活性与 CLT 显著相关。纤溶蛋白单核苷酸多态性分析显示,病例组与对照组之间无显著差异。这项病例对照研究首次提供了证据表明,纤溶潜能受损,至少部分是由于 PAI-1 水平升高引起的,与 BCS 的存在有关。