[Local thrombolysis in peripheral arterial occlusion]

Abstract

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)