Authors: Victor Gurewich.
Therapeutic fibrinolysis has used tissue plasminogen activator (tPA) since 1987 based on a belief that tPA was responsible for biological fibrinolysis. This belief, however, was belied by clinical experience with tPA showing that it was not an effective fibrinolytic. Comparative clinical trials in almost 100,000 patients with acute myocardial infarction (AMI) failed to show that tPA was unequivocally more effective than streptokinase (SK), an indirect, inefficient, and non-specific plasminogen activator. Instead, it was found that tPA caused significantly more intracranial hemorrhage (ICH) side effects than SK. This disappointing experience led to the abandonment of fibrinolysis and its replacement by percutaneous coronary intervention (PCI) for AMI. However, PCI is a time-consuming, hospital procedure, poorly adapted to salvaging function of an ischemic myocardium, for which success is critically time dependent. Fibrinolysis remains the fastest method available for this and its abandonment is predicated on fibrinolysis and tPA being identical. This assumption, however, is contradicted by evidence that fibrinolysis requires both biological plasminogen activators, and that urokinase plasminogen activator (uPA) is the dominant of the two. This was also documented in a single clinical study in AMI, in which tPA’s fibrinolytic function was found to be analogous to that of the starter in an automobile.
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