FIBRINOLYSIS WAS REPLACED BEFORE IT WAS UNDERSTOOD.

Introduction Fibrinolysis is often wrongly believed to be due to tissue plasminogen activator (tPA) alone. Instead, both endogenous plasminogen activators are required, but only a mini bolus of tPA is needed to initiate fibrinolysis. This is due to tPA's unique high fibrin affinity binding site located on the fibrin D-domain. Both activators are present in all normal plasma, consistent with both being involved in biological fibrinolysis, which is also the model for optimal therapeutic fibrinolysis. Methods This uses a sequential combination of a 5 mg mini bolus of tPA followed by an infusion of proUK (40 mg/hr) for 90 minutes. This treatment is both highly effective and free of side effects. Results By contrast, due to a misunderstanding of fibrinolysis, tPA is often administered alone. This requires doses of 90-100 mg of tPA over 60 minutes, which is neither very effective nor safe, due to a risk of bleeding complications from the lysis of hemostatic fibrin by tPA's fibrin affinity. Due to this problem, fibrinolysis was replaced by interventional procedures, like percutaneous coronary intervention (PCI), which is much slower, limited to clots larger than the catheter, but is generously reimbursed by third party payers.