What Fibrinolytic Therapy can Learn from Natural Fibrinolysis: Both Activators are a Requirement

Fibrinolytic therapy with tissue Plasminogen Activator (tPA) alone has been the standard for three decades, but due to its inefficacy and bleeding risk, tPA has been replaced by Primary Percutaneous Coronary Intervention (PPCI) as the treatment of choice for Acute Myocardial Infarction (AMI). By contrast to tPA mono-therapy, natural fibrinolysis uses a sequential combination of both biological activators, tPA and uPA, the native form of which is a proenzyme, prouPA. Both in vitro and in vivo, tPA and prouPA have complementary modes of action in fibrinolysis are synergistic when combined. In a published clinical trial, the patent study, 101 patients with AMI were treated with a 5 mg tPA bolus (5% of the standard monotherapy dose) followed by a modest infusion of prouPA. This sequential combination virtually doubled the coronary TIMI-3 infarct artery patency rate and reduced the mortality six-fold compared to the best results with tPA alone. Citation: Gurewich V (2018) What Fibrinolytic Therapy can Learn from Natural Fibrinolysis: Both Activators are a Requirement. J Non Invasive Vasc Invest 3: 010.