Nielsen Vance G, Steenwyk Brad L, Gurley William Q
Department of Anesthesiology, University of Alabama at Birmingham, 619 South 19th Street, Birmingham, AL 35249-6810, USA.
J Heart Lung Transplant. 2006 Oct;25(10):1247-52. doi: 10.1016/j.healun.2006.06.009.
Contact activation system proteins (e.g., Factor XII, kallikrein) have been implicated as direct or indirect activators of plasminogen. However, contact activation and Factor XI have enhanced thrombin-activatable fibrinolysis inhibitor (TAFI) activation and decreased fibrinolysis, and Factor XIII (FXIII) also delays fibrinolysis via alpha(2)-anti-plasmin deposition on fibrin polymers. Thus, the goals of this study were to define how fibrinolysis is modulated in human plasma by contact or tissue factor (TF) activation, and what role TAFI and FXIII plays in this system.
Normal, TAFI-deficient and TAFI-deficient/FXIII-supplemented plasma was exposed to tissue-type plasminogen activator and activated with either celite or TF. Clot growth/disintegration kinetics were documented with thrombelastography.
Normal plasma activated with celite had significantly prolonged onset and duration of clot lysis compared with samples activated with TF. TAFI-deficient plasma activated with celite was noted to have a duration of clot lysis not different from samples activated with TF, but a significant difference in time to onset of lysis persisted. Celite activation of TAFI-deficient/FXIII-supplemented plasma showed significantly prolonged onset and duration of clot lysis compared with samples activated with TF.
Primarily TAFI, and to a lesser extent FXIII, contributed to contact system protein-mediated attenuation of fibrinolysis. Clinical investigation of these phenomena is warranted in clinical settings involving contact activation (e.g., intra-aortic balloon pumps and ventricular assist devices) to determine whether these devices modulate fibrinolysis and perhaps contribute to thromboembolic morbidity.
接触激活系统蛋白（如因子 XII、激肽释放酶）被认为是纤溶酶原的直接或间接激活剂。然而，接触激活和因子 XI 可增强凝血酶激活的纤溶抑制物（TAFI）的激活并降低纤溶作用，并且因子 XIII（FXIII）也通过α2-抗纤溶酶在纤维蛋白聚合物上的沉积延迟纤溶。因此，本研究的目的是确定在人血浆中接触或组织因子（TF）激活如何调节纤溶，以及 TAFI 和 FXIII 在该系统中起什么作用。
将正常、缺乏 TAFI 和补充了 FXIII 的缺乏 TAFI 的血浆暴露于组织型纤溶酶原激活剂，并用硅藻土或 TF 激活。用血栓弹力图记录凝块生长/溶解动力学。
与用 TF 激活的样品相比，用硅藻土激活的正常血浆的凝块溶解起始时间和持续时间显著延长。用硅藻土激活的缺乏 TAFI 的血浆的凝块溶解持续时间与用 TF 激活的样品没有差异，但溶解起始时间仍存在显著差异。与用 TF 激活的样品相比，用硅藻土激活补充了 FXIII 的缺乏 TAFI 的血浆显示凝块溶解起始时间和持续时间显著延长。
主要是 TAFI，其次是 FXIII，导致接触系统蛋白介导的纤溶减弱。在涉及接触激活的临床环境（如主动脉内球囊泵和心室辅助装置）中，对这些现象进行临床研究是有必要的，以确定这些装置是否调节纤溶，以及是否可能导致血栓栓塞性发病。
