Intravenous administration of an agent intended to dissolve a clot causing acute ischemia, as in myocardial infarction (MI), stroke, and peripheral arterial or venous thrombosis. Thrombolytic agents degrade fibrin clots by activating plasminogen, a naturally occurring modulator of hemostatic and thrombotic processes. Synthesized by the liver, plasminogen is present in circulating blood and binds to platelets, endothelium, and fibrin. At sites of vascular injury with thrombus formation, tissue plasminogen activator (TPA), produced by endothelial cells, also binds to fibrin and converts fibrin-bound plasminogen to plasmin by cleaving the arginine-valine bond in the 560–561 position of plasminogen. The resulting clot lysis is due to degradation of fibrin threads as well as of glycoproteins required for platelet adhesion and aggregation. Thrombolytic agents in current use mimic the effects of natural TPA. These include alteplase, a TPA produced by recombinant DNA technology; reteplase, a variant of the TPA molecule, also genetically engineered; urokinase, a tissue protein derived from human kidney cell cultures; streptokinase, a product of *-hemolytic streptococci that catalyzes the conversion of plasminogen to plasmin; and anistreplase, an inactive form of plasminogen that is bound to streptokinase and undergoes deacylation after administration, resulting in persistent activation of plasminogen. The latter two products are potentially antigenic and can cause systemic hypersensitivity reactions. See Also: tissue plasminogen activator. Thrombolytic therapy reduces the in-hospital and 1-year mortality of acute MI by 20–40% when administered promptly (within the first 100 minutes). Some benefit may accrue even after a delay of 6–12 hours. About half those treated for acute MI with a thrombolytic agent have patent coronary arteries after 90 minutes. However, 30% experience reinfarction at the same site within 3 months. Emergency percutaneous transluminal coronary angioplasty (PTCA) may provide better survival figures, but can only be undertaken in a setting where emergency coronary artery bypass graft (CABG) is feasible in case of failure. Streptokinase has sometimes been preferred to TPA in acute MI because it is much less expensive. However, an exhaustive analysis has shown that the use of TPA is cost effective, particularly in anterior MI. That thrombolytic drugs activate platelets partially negates their effectiveness. Combining heparin and the platelet inhibitor abciximab with TPA enhances its ability to restore arterial patency in acute MI. In ischemic stroke, administration of TPA within the first 3 hours has been shown to improve overall outcome at 90 days. The usefulness of thrombolytic therapy in stroke is limited by the difficulty of excluding hemorrhagic stroke and the risk of hemorrhage as a side-effect of therapy. Only TPA is currently recommended in the treatment of stroke. In addition to stroke and MI, thrombolytic therapy has been used in pulmonary embolism, deep venous thrombosis, and peripheral arterial occlusion. Thrombolytic therapy in acute occlusion of a lower-limb artery (or ABG) can obviate the need for surgery in many patients without increasing mortality or amputation rate. Recanalization occurs in as many as 80% of patients. The chief risk of thrombolytic therapy is major hemorrhage. It is contraindicated in the presence of active or recent hemorrhage, active diabetic hemorrhagic retinopathy, recent surgery, intracranial neoplasm or recent head trauma, history of prior hemorrhagic stroke, aortic dissection, acute pericarditis, prolonged or traumatic CPR, pregnancy, or sensitivity to the specific agent. Reference: Stedman's Medical Dictionary
