ABSTRACT
Thrombolysis consists of the pharmacological dissolution of a blood clot by administration of agents that activate the fibrinolytic system. The fibrinolytic system includes a proenzyme, plasminogen, which is converted by plasminogen activators to the active enzyme plasmin, which in turn digests fibrin to soluble degradation products. Inhibition of the fibrinolytic system occurs at the level of the plasminogen activator (by plasminogen activator inhibitors, mainly plasminogen activator inhibitor 1, PAI-1) and at the level of plasmin (by plasmin inhibitors, mainly α2-antiplasmin). Presently available thrombolytic agents include streptokinase, recombinant tissue-type plasminogen activator (rtPA, alteplase), rtPA derivatives (e.g. reteplase, lanoteplase, monteplase, and tenecteplase), anisoylated plasminogen-streptokinase activator complex (APSAC, anistreplase), twochain urokinase-type plasminogen activator (tcuPA, urokinase), recombinant single-chain uPA (scuPA, prourokinase, saruplase), and recombinant staphylokinase and derivatives. Fibrin-selective agents (rtPA and derivatives, staphylokinase and derivatives, and to a lesser extent scuPA), which digest the clot in the absence of systemic plasminogen activation are distinguished from non-fibrin-selective agents (streptokinase, tcuPA, and APSAC), which activate systemic and fibrin-bound plasminogen relatively indiscriminately (Figure 3.1).1,2 Some of these newer derivatives are under clinical investigation, mainly in patients with acute myocardial infarction (AMI), but also in those with deep vein thrombosis, peripheral arterial occlusion, pulmonary embolism, and ischemic stroke. In this chapter, we shall review the main properties of fibrinolytic agents with therapeutic potential.
