A detailed USMLE-style medical flowchart of fibrinolysis showing all enzymes, activators, and inhibitors. The flowchart should include: ACTIVATORS section (top): - tPA (tissue plasminogen activator) - released from vascular endothelium, stimulated by activated Protein C (APC) and bradykinin - uPA (urokinase-type plasminogen activator) - single-chain (1c-uPA) activated to two-chain (2c-uPA) by Factor XIIa and Kallikrein - Streptokinase (exogenous, from beta-hemolytic Streptococcus) - allosteric modifier, forms streptokinase-plasminogen complex CENTRAL PATHWAY (middle): - Plasminogen (zymogen, binds fibrin via c-lysine residues) → [tPA / uPA / Streptokinase] → Plasmin (active serine protease) - Fibrin (cofactor, increases tPA activity 1000x) → Fibrin Degradation Products (FDP / D-dimer) - Plasmin cleaves cross-linked fibrin → FDPs cleared by liver CONTACT ACTIVATION pathway: - Factor XII → Factor XIIa → activates Prekallikrein → Kallikrein (with HMWK cofactor) - Kallikrein → activates 1c-uPA to 2c-uPA; Kallikrein cleaves HMWK → Bradykinin → stimulates endothelium to release tPA INHIBITORS section (bottom, with red inhibitory arrows): - PAI-1 (Plasminogen Activator Inhibitor-1, serpin) → inhibits tPA and uPA → forms tPA-PAI-1 complex (cleared by liver) - α2-Antiplasmin (serpin, crosslinked to fibrin by Factor XIIIa) → inhibits free circulating Plasmin → forms PAP complex (cleared by liver) - TAFIa (Thrombin-Activatable Fibrinolysis Inhibitor) → activated by Thrombin-Thrombomodulin complex → cleaves c-lysine residues from fibrin → prevents plasminogen binding DRUG TARGETS box: - tPA drugs: Alteplase, Tenecteplase (TNK), Reteplase (rPA) - Non-fibrin-specific: Streptokinase - All convert plasminogen → plasmin → dissolve fibrin clot Use blue arrows for activation, red flat-headed arrows for inhibition, green boxes for enzymes/active forms, yellow boxes for zymogens, orange boxes for inhibitors. Clean white background with clear labels and professional medical diagram style.