Hess H
Privatklinik Josephinum, München.
Herz. 1989 Feb;14(1):12-21.
Peripheral arterial occlusions, with the exception of those induced mechanically or by vasospasm, are invariably caused by a blood clot resulting from either in-situ thrombosis or embolism. More than 10% of embolic occlusions in otherwise healthy arteries undergo spontaneous lysis due to the organisms tissue plasminogen activator. In thrombotic occlusion of arteriosclerotic vessels, probably due to insufficient activator release from the diseased arterial wall, spontaneous lysis is much less common. For more than 25 years, lysis has been aided with streptokinase (SK) or urokinase (UK) which, until eight years ago, had only been given systemically with a standard dosage of 2.4 million units daily for up to five days. Thrombotic femoral artery occlusions of up to six weeks old were successfully lysed in 48%, six to twelve weeks old in 25% and, in those older than twelve weeks only in exceptional cases. With embolic occlusion, systemic lysis is contraindicated due to the possibility of provoking new emboli. With conventional systemic SK treatment, in 7% of the patients there was severe bleeding which in 1.12% was fatal. The ultrahigh SK treatment (nine million units in six hours) has substantially fewer bleeding complications but no better rate of success. Systemic administration of SK and UK leads to activation of the entire circulating plasminogen and the correspondingly-associated clotting defects. Recombinant tissue plasminogen activator (rt-PA), the production of which was rendered possible by genetic engineering, is identical to human tissue activator, has a high affinity to fibrin-bound plasminogen, less affinity to circulating plasminogen. After systemic administration, however, the plasminogen in every vascular clot is activated such that, even without alteration of the clotting system, bleeding the emboli can be provoked. With local application of the activator, even extensive clots, provided they contain lysable fibrin, can be dissolved within one-half to three hours with comparably minimal doses. For local lysis treatment of peripheral arterial occlusions, SK, UK and rt-PA are well-suited. With a total dose of maximally 30,000 units SK, in contrast to the initially-used higher doses, there were no bleeding complications in more than 300 patients. Even with a total doses of 100,000 to 300,000 UK, albeit in a relatively small number of patients, and a total dose of 2.5 to 7.5 mg rt-PA which was given within three hours maximally to 85 patients, there were no bleeding complications.(ABSTRACT TRUNCATED AT 400 WORDS)
外周动脉闭塞,除机械性或血管痉挛所致者外,均由原位血栓形成或栓子所致的血凝块引起。在原本健康的动脉中,超过10%的栓塞性闭塞会因机体组织纤溶酶原激活剂而自发溶解。在动脉粥样硬化血管的血栓形成性闭塞中,可能由于病变动脉壁释放的激活剂不足,自发溶解则较为少见。25多年来,链激酶(SK)或尿激酶(UK)一直用于辅助溶解血栓,直到8年前,它们一直以每日240万单位的标准剂量全身给药,持续5天。长达6周的股动脉血栓形成性闭塞,48%成功溶解;6至12周的,25%成功溶解;而在12周以上的患者中,仅在特殊情况下成功溶解。对于栓塞性闭塞,由于可能引发新的栓子,禁忌全身溶栓。采用传统的全身SK治疗,7%的患者出现严重出血,其中1.12%致命。超高剂量SK治疗(6小时内900万单位)出血并发症明显减少,但成功率并未提高。全身给予SK和UK会激活整个循环中的纤溶酶原,并相应地引发凝血缺陷。重组组织纤溶酶原激活剂(rt-PA),通过基因工程得以生产,与人体组织激活剂相同,对纤维蛋白结合的纤溶酶原具有高亲和力,对循环中的纤溶酶原亲和力较低。然而,全身给药后,每个血管内血栓中的纤溶酶原都会被激活,这样即使不改变凝血系统,也可能引发栓子出血。局部应用激活剂,即使是广泛的血栓,只要含有可溶解的纤维蛋白,用相对较小的剂量在半小时至三小时内即可溶解。对于外周动脉闭塞的局部溶栓治疗,SK、UK和rt-PA都很适用。与最初使用的较高剂量相比,最大总剂量为30000单位SK时,300多名患者未出现出血并发症。即使总剂量为100000至300000单位UK(尽管患者数量相对较少),以及最大总剂量为2.5至7.5毫克rt-PA在三小时内给予最多85名患者,也未出现出血并发症。(摘要截选至400字)