Bode C, Runge M S, Haber E
Medical Clinic III (Cardiology), University of Heidelberg, Federal Republic of Germany.
Clin Cardiol. 1990 Jun;13(6):375-81. doi: 10.1002/clc.4960130602.
Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule.
诸如心肌梗死和中风等血栓形成性疾病是工业化国家死亡和残疾的主要原因。及时进行溶栓治疗可缩小梗死面积、保护左心室功能并降低死亡率。链激酶、尿激酶和酰化纤溶酶原 - 链激酶激活剂复合物（APSAC）的使用可能会导致止血系统完全崩溃。组织型纤溶酶原激活剂（t-PA）和单链尿激酶型纤溶酶原激活剂（scu-PA，尿激酶原）对纤维蛋白具有更高的特异性；然而，为达到治疗效果所需的大剂量激活剂仍会引发出血并发症。通过在不牺牲特异性的情况下提高疗效来优化患者风险/收益比的新方法包括使用纤溶酶原激活剂的协同组合、t-PA和scu-PA的突变体、嵌合分子以及抗体靶向溶栓剂。最后一种方法使得在一个优化分子中利用纤溶或抗血小板效应功能靶向血凝块的几种不同成分成为可能。
