Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure.
Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure.
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DOI：
10.1182/blood.v82.8.2462.2462
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发表时间：
1993-10
期刊：
影响因子：
20.3
通讯作者：
J. Collet;J. Soria;M. Mirshahi;M. Hirsch;F. Dagonnet;J. Caen;C. Soria
中科院分区：
文献类型：
--
作者：
J. Collet;J. Soria;M. Mirshahi;M. Hirsch;F. Dagonnet;J. Caen;C. Soria
纤维蛋白原Dusart是一种先天性异常纤维蛋白原血症（A-α 554精氨酸->半胱氨酸），与严重血栓性疾病、血栓栓塞的高发生率和异常纤维蛋白聚合相关。这种血栓性疾病归因于异常的凝块血栓溶解，纤溶酶原与纤维蛋白结合减少，组织纤溶酶原激活剂对纤溶酶原的激活缺陷。这项工作的目的是评估凝块结构是否可能参与纤维蛋白Dusart的抗血栓性和栓塞的高发生率。Dusart纤维蛋白凝块结构的一个重要变化是通过渗透分析得出的凝胶孔隙率（Ks）、纤维直径（d）和纤维质量-长度比（mu）的显著降低来确定的。此外，发现Dusart凝块的硬度与正常纤维蛋白相比大大增加。我们提供的证据表明，溶栓阻力和异常刚性的纤维蛋白Dusart相关的这种异常的架构，这损害了纤维蛋白溶解酶的访问纤维蛋白，这是一个脆性的凝块，很容易打破，导致栓塞的发生率高。事实上，当通过在凝血前添加右旋糖酐40（30 mg/mL）来恢复正常的凝块结构时，凝块血栓溶解和凝块硬度恢复正常值。发现该效应具有剂量依赖性。我们的结论是，凝块结构是至关重要的倾向，血液凝块被降解，异常凝块结构可以在体内高度血栓形成。纤维蛋白原的α-C结构域是纤维蛋白凝块结构的决定因素。
Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose-dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.