UMRS 872 INSERM, Université Pierre et Marie Curie Paris VI and Université René Descartes, Paris, France.
Thromb Res. 2013 Mar;131(3):e100-9. doi: 10.1016/j.thromres.2012.11.029. Epub 2013 Jan 11.
Defective thrombolysis, a thrombotic risk factor, can be attributed to the formation of a compact clot poorly accessible to fibrinolytic enzymes. Venous thrombi, rich in red blood cells (RBCs), and arterial thrombi containing various amounts of RBCS, plasma and whole blood (WB) clot permeability and degradability were compared. The effect of rivaroxaban, a potent direct factor Xa inhibitor, was also evaluated.
Fibrin permeability was determined by flow measurement through the clot. Clot degradability was evaluated by the amount of D-dimer generated by clot perfusion with plasminogen and tissue plasminogen activator. Fibrin clot structure was assessed by confocal microscopy.
WB clot permeability (KS) and degradability were 6.7- and 38-fold lower, respectively, compared with plasma clots. This is attributed to 1) occlusion of fibrin pores by RBCs and 2) a consistent increase in thrombin generation due to platelets and RBCs inducing formation of a tighter clot. Rivaroxaban added to plasma or WB before clotting, in reducing thrombin generation, led to the formation of a looser clot that is more degradable by fibrinolytic enzymes. Permeability and degradability of whole blood clots formed in the presence of rivaroxaban were very similar to those of plasma clots.
The resistance to fibrinolysis of WB clots was reduced considerably when clots were formed with rivaroxaban. These results may have implications for the development of antithrombotic agents.
溶栓缺陷是一种血栓形成的危险因素，可归因于不易被纤维蛋白溶解酶溶解的致密血栓形成。本研究比较了富含红细胞（RBC）的静脉血栓和含有不同数量 RBC、血浆和全血（WB）的动脉血栓的渗透性和降解性。还评估了强效直接因子 Xa 抑制剂利伐沙班的作用。
通过纤维蛋白渗透性测定法通过血栓测量流量。通过用纤溶酶原和组织型纤溶酶原激活物灌注血栓来评估血栓降解性，通过产生的 D-二聚体的量来评估。通过共聚焦显微镜评估纤维蛋白血栓结构。
与血浆血栓相比，WB 血栓的渗透性（KS）和降解性分别低 6.7 倍和 38 倍。这归因于 1）RBC 阻塞纤维蛋白孔，以及 2）由于血小板和 RBC 诱导形成更紧密的血栓，凝血酶生成一致增加。利伐沙班在凝血前添加到血浆或 WB 中，通过减少凝血酶生成，导致形成更松散的血栓，对纤维蛋白溶解酶的降解性更强。在利伐沙班存在下形成的 WB 血栓的渗透性和降解性与血浆血栓非常相似。
当用利伐沙班形成血栓时，WB 血栓的纤溶抵抗性大大降低。这些结果可能对开发抗血栓形成药物具有重要意义。
