Unanswered questions in thrombolysis

Data available experimentally and from major trials suggest that the beneficial effects of thrombolysis depend on more than simple reperfusion. New knowledge regarding the dynamic nature of clot formation and clot lysis enables us to understand more of the processes involved in thrombolysis. The breakdown of systemic fibrinogen may be important because of the anticoagulant effect this can produce. Other beneficial effects of thrombolysis remain unproved or obscure. It is unlikely that any thrombolytic agent can be completely free of risk because no distinction is possible between a hemostatic plug and a pathologic thrombus. There may, however, be differences between agents in the likelihood of reocclusion. The value of active intervention with angioplasty or bypass grafting after thrombolysis remains undefined. Three major trials suggest that little erosion of initial benefit occurs over the first 12 months even when management is largely conservative. If thrombolysis leads to smaller infarct size, however, prognosis should be influenced favorably over a prolonged period. Parallel mortality curves between treated and placebo groups therefore suggest that some attrition is occurring to counteract what might otherwise be continuing prognostic benefit. The ideal thrombolytic agent should be inexpensive to manufacture, have a low risk of hemorrhagic complications, be nonallergenic, provide rapid and complete thrombolysis, have some anticoagulant properties, be easy to administer and suitable for readministration. However, a low risk of hemorrhage is probably incompatible with effective thrombolysis. A comparison of mortality results with the 3 existing agents are awaited with interest.