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JAMA. 1961;175(4):316. doi:10.1001/jama.1961.03040040048010.
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Great advances have been made in the control of thromboembolic diseases, primarily by prophylactic measures including early ambulation and anticoagulants. Despite these measures morbidity and mortality remain very high, and there seems little promise of much improvement by these means. Once a thrombosis is established, they can only prevent further extension.

The logical therapeutic agent is one which would dissolve thrombi within the circulation. Since fibrin is the material which effectively maintains the clot until fibrosis or endothelization occurs, a fibrinolytic agent is necessary (fibrinolysin). This agent must be effective in dissolving the fibrin binding the clot without affecting adversely the other proteins in the blood or producing adverse side reactions. Obvious possibilities include hemorrhage, particularly in patients after operation, and embolization due to partial lysis of the clot. Bleeding has been rare even in patients considered unsafe for anticoagulants, and pulmonary emboli have been very rarely, if ever, seen


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