Brommer E J, van Bockel J H
Gaubius Laboratorium IVVO-TNO, Leiden, The Netherlands.
Blood Coagul Fibrinolysis. 1992 Dec;3(6):717-25. doi: 10.1097/00001721-199212000-00003.
Each of three distinct, concentric layers of human arterial thrombi, was analysed immunochemically for the plasminogen and fibrin content, and for the ex vivo susceptibility to thrombolysis by various thrombolytic agents in a saline or plasma milieu. The age of the thrombus layer determined: (a) the plasminogen content; (b) the fibrin content, inferred from the recovery of fibrin degradation products after complete lysis and from the binding of a monoclonal anti-fibrin antibody in a perfusion system, and (c) the lysibility of the thrombus. Plotting concentration of the various thrombolytic agents against percentage of lysis at several time points allows for reading of equivalent potencies of the respective units. Undiluted solutions of APSAC and rt-PA, prepared according to the manufacturer's directions, were less effective than diluted solutions, which has consequences for local therapy. All agents were at least as effective in saline as in a plasma milieu. We conclude that the plasminogen content of aged arterial thrombi is sufficient for complete and rapid thrombolysis. Only after several months do fibrin and plasminogen become so far degraded or replaced that the thrombi become resistant to thrombolysis.
对人动脉血栓的三个不同的同心层分别进行免疫化学分析,检测其纤溶酶原和纤维蛋白含量,以及在生理盐水或血浆环境中对各种溶栓剂体外溶栓的敏感性。血栓层的年龄决定了:(a)纤溶酶原含量;(b)纤维蛋白含量,通过完全溶解后纤维蛋白降解产物的回收率以及灌注系统中一种单克隆抗纤维蛋白抗体的结合情况推断得出;(c)血栓的可溶解性。在几个时间点绘制各种溶栓剂的浓度与溶解百分比的关系图,可以读出各单位的等效效力。按照制造商说明制备的未稀释的茴香酰化纤溶酶原链激酶激活剂复合物(APSAC)和重组组织型纤溶酶原激活剂(rt-PA)溶液比稀释溶液效果差,这对局部治疗有影响。所有药物在生理盐水中至少与在血浆环境中一样有效。我们得出结论,陈旧性动脉血栓的纤溶酶原含量足以实现完全且快速的溶栓。只有在几个月后,纤维蛋白和纤溶酶原才会降解或被替换到血栓对溶栓产生抵抗的程度。