ABSTRACT
Thrombolysis consists of the pharmacological dissolution of a blood clot by administration of thrombolytic agents that activate the fibrinolytic system. This system includes a proenzyme, plasminogen, which is converted by plasminogen activators (PAs) to the active enzyme plasmin, which in turn digests fibrin to soluble degradation products. There are two physiologic plasminogen activators: the tissue-type (t-PA; EC 3.4.21.68) and the urokinase-type (u-PA; EC 3.4.21.73). Inhibition of the fibrinolytic system occurs at the level of PA by plasminogen activator inhibitors (PAI, mainly PAI-1 and in some conditions PAI-2) and at the level of plasmin by plasmin inhibitors (mainly a2antiplasmin) (Fig. 1). Presently available plasminogen activators include serine proteinases such as recombinant t-PA (rt-PA or alteplase) and its derivatives, two-chain u-PA (tcu-PA or urokinase) and recombinant single-chain u-PA (scu-PA or prourokinase, saruplase) as well as nonenzyme plasminogen activators such as streptokinase, anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase), and recombinant staphylokinase and derivatives. Traditionally, these were classified as fibrinselective agents (rt-PA and derivatives, staphylokinase and derivatives, and to a lesser extent scu-PA), which digest a thrombus in the absence of systemic plasminogen activation, or as nonfibrin-selective agents (streptokinase, tcu-PA, and APSAC), which activate systemic and fibrin-bound plasminogen relatively indiscriminately (1,2). More recently, thrombolytics that act directly on fibrin have also been characterized and evaluated, including different molecular forms of plasmin as well as several fibrinolytic enzymes derived from snake venoms. In this contribution, we will review the main properties of fibrinolytic agents with therapeutic potential. Clinical experience in patients with acute myocardial infarction, deep vein thrombosis, pulmonary hypertension, and ischemic stroke will be discussed in the next chapters.
