Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics, Health and Therapeutics, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK.
Thromb Res. 2019 Feb;174:88-94. doi: 10.1016/j.thromres.2018.12.004. Epub 2018 Dec 4.
Enhanced clot lysis is associated with bleeding, but assessment of lysis capacity remains difficult. The plasma turbidity lysis and whole blood tissue Plasminogen Activator-Rotational Thromboelastometry (tPA-ROTEM) assays estimate fibrinolysis under more physiological conditions than clinically used assays. We hypothesized that these assays could find signs of enhanced lysis capacity in patients who report bleeding symptoms, but are not diagnosed with bleeding disorders. We also aimed to gain insight in determinants of the results of these lysis assays. Data from 240 patients with and 95 patients without self-reported bleeding symptoms were obtained, who were included in a study that primarily aimed to assess prevalence of haemostatic abnormalities in preoperative patients. ROTEM and turbidity assays were performed with rtPA. Blood counts, fibrinolysis and coagulation factor activities were determined. Data were analysed using multivariable linear regression models. Remarkably, patients reporting bleeding symptoms showed signs of significantly impaired lysis capacity in the tPA-ROTEM, but not in the turbidity lysis assay. In these patients, the tPA-ROTEM results depended on FII, FXII, plasminogen, α2-antiplasmin, PAI-1 and TAFI levels. The turbidity lysis results were significantly influenced by fibrinogen, α2-antiplasmin, PAI-1 and TAFI. In conclusion, the tPA-ROTEM and the turbidity lysis assay could not detect enhanced fibrinolytic capacity in patients with bleeding symptoms. This suggests that these symptoms are not caused by enhanced fibrinolytic activity. As both assays were sensitive to important determinants of fibrinolysis they may be able to detect a fibrinolytic imbalance, but this needs to be validated in patients with known hypo- or hyperfibrinolytic disorders.
纤溶增强与出血相关，但纤溶能力的评估仍然很困难。与临床应用的检测方法相比，血浆浊度法纤溶检测和全血组织型纤溶酶原激活物-旋转血栓弹性测定法（tPA-ROTEM）检测更能反映生理条件下的纤溶情况。我们假设这些检测方法可以在报告出血症状但未被诊断为出血性疾病的患者中发现纤溶能力增强的迹象。我们还旨在深入了解这些纤溶检测结果的决定因素。我们获得了 240 例有和 95 例无自我报告出血症状的患者的数据，这些患者被纳入一项主要旨在评估术前患者止血异常发生率的研究中。使用 rtPA 进行 ROTEM 和浊度检测。测定血细胞计数、纤溶和凝血因子活性。使用多变量线性回归模型进行数据分析。值得注意的是，报告出血症状的患者在 tPA-ROTEM 中显示出明显的纤溶能力受损迹象，但在浊度纤溶检测中没有。在这些患者中，tPA-ROTEM 结果取决于 FII、FXII、纤溶酶原、α2-抗纤溶酶、PAI-1 和 TAFI 水平。浊度纤溶结果受纤维蛋白原、α2-抗纤溶酶、PAI-1 和 TAFI 的显著影响。总之，tPA-ROTEM 和浊度纤溶检测不能检测到有出血症状的患者的纤溶能力增强。这表明这些症状不是由增强的纤溶活性引起的。由于这两种检测方法都对纤溶的重要决定因素敏感，它们可能能够检测到纤溶失衡，但这需要在已知存在低纤维蛋白溶解或高纤维蛋白溶解障碍的患者中进行验证。
