Thrombolysis, the only Optimally Rapid Reperfusion Treatment

Abstract

Thrombolysis with tissue plasminogen activator (tPA) has been plagued by inadequate effi cacy and a high risk of intracranial hemorrhage (ICH), which led to its replacement by procedures like percutaneous coronary intervention (PCI) whenever possible. Since this requires hospitalization, it is time-consuming, and compromising salvage of brain tissue and myocardium. Thrombolysis is the only fi rst-line treatment that can provide suffi ciently timely treatment for optimal recovery of organ function. However, for this potential to be realized, its effi cacy and safety must be signifi cantly improved over the current method. By adopting the sequential, synergistic fi brinolytic paradigm of the endogenous system, already verifi ed by a clinical trial, this becomes possible. The endogenous system's function is evidenced by the fi brinolytic product D-dimer that is invariably present in blood, and which increases >20-fold in the presence of thromboembolism. This system uses tPA to initiate lysis, which is then completed by the other fi brin-specifi c activator prourokinase (proUK). Since tPA and proUK in combination are synergistic in fi brinolysis, it helps explain their effi cacy at their low endogenous concentrations.