Tissue Plasminogen Activator-Based Thrombolytic Agents

This chapter focuses on tissue plasminogen activator (tPA)-based product variants approved for general medical use: Alteplase, Reteplase, and Tenecteplase. Fibrinolysis is a proteolytic-mediated process initiated by tPA, which activates the protein plasminogen, thereby forming plasmin. Human tPA was first purified from uterine tissue in 1979, and ensuing immunological studies illustrated that tissue, vascular, and blood-derived plasminogen activators are the same. Alteplase is a first-generation recombinant human tPA approved for general medical use in the United States in 1987. Alteplase is synthesized using the complementary deoxyribonucleic acid for native human tPA derived from a human melanoma cell line. The therapeutic rationale for developing Tenecteplase was the generation of a tPA variant that can be administered intravenously as a rapid single-dose bolus injection. Therapeutic drugs aimed at minimizing the formation and reformation of such thrombi, or accelerating the removal of thrombi once formed, include antiplatelet agents, thrombolytic therapy, and the administration of anticoagulants.