Clinical meaning
The fibrinolytic system is the body's endogenous mechanism for dissolving blood clots after vascular repair is complete. Plasminogen, a circulating inactive zymogen, is converted to plasmin by tissue plasminogen activator (tPA), which is released from endothelial cells. Plasmin cleaves fibrin within clots into fibrin degradation products (including D-dimer, which is why D-dimer is elevated after physiological fibrinolysis and with thrombolytic therapy). The system is regulated by plasminogen activator inhibitor-1 (PAI-1), which inhibits tPA, and alpha-2-antiplasmin, which neutralizes circulating plasmin. Therapeutic thrombolytics are exogenous activators of this system: Alteplase (tPA) is a recombinant tissue plasminogen activator with relative fibrin specificity — it preferentially activates plasminogen bound to fibrin in the clot, causing less systemic fibrinolysis than non-specific agents; however, at therapeutic doses, systemic fibrinolysis still occurs. Tenecteplase is a genetically modified tPA with longer half-life (allowing single IV bolus dosing), greater fibrin specificity, and greater resistance to PAI-1 inactivation. Reteplase is another modified tPA given as two IV boluses 30 minutes apart. Streptokinase (historical) is a bacterial protein that forms a complex with plasminogen, directly activating it; non-fibrin-specific, causes extensive systemic fibrinolysis; antigenic (can cause allergic reactions); rarely used in developed countries. Clinical indications: acute STEMI (most common indication — PCI preferred but thrombolytics when PCI unavailable within 120 minutes), acute ischemic stroke (alteplase within 4.5 hours of symptom onset), massive PE with hemodynamic instability, and occasionally acute arterial limb ischemia or thrombosed prosthetic heart valve.