The fibrinolytic system is the most important anticoagulation system in the body. During the lysis process, thrombin hydrolyzes fibrin, releasing soluble fibrin monomers, which form stable cross-linked fibrin under the action of factor xIIIa. In late stages of disseminated intravascular coagulation, the fibrinolytic system is activated due to intravascular coagulation, resulting in secondary fibrinolysis and more pronounced bleeding symptoms. What can cause secondary hyperfibrinolysis? Secondary hyperfibrinolysis, such as thrombophilia and DIC, is caused by enhanced coagulation mechanisms in the pre-disease period and massive fibrin production, which subsequently causes hyperfibrinolysis. Increased fibrinogen activator Tissues such as lung, pancreas, prostate, thyroid and uterus contain more abundant fibrinogen activator. When tumors or surgery occur in these organs, a large amount of tissue fibrinogen activator is released into the blood circulation, which can cause protofibrinogenesis. Amniotic fluid can induce strong fibrinolytic activity, so amniotic fluid embolism and early placental abruption, when the amniotic fluid enters the mother, can also cause protofibrin. In severe hypoxia, heat stroke and shock, vascular endothelial cells are damaged and the fibrinogen activator they contain is released into the blood circulation, which can also promote protofibrillation. According to statistics, protofibrillation occurs in 75-85% of patients receiving extracorporeal circulation. The mechanism is unclear and may be due to the activation of the fibrinolytic system by enzymes of the coagulation and fibrinolytic systems in contact with extracorporeal circulation devices or abnormal vascular surfaces. In addition, an excess of streptokinase and urokinase during thrombolytic therapy can lead to massive formation of fibrinolytic enzymes and cause protofibrillation. The liver is the site of synthesis of the fibrinolytic inhibitor α2 antifibrinolytic enzyme (α2AP or α2PI) and inactivation of fibrinogen activator. When liver parenchymal cells are severely damaged, such as in cirrhosis, severe hepatitis, during the liver transplantation anaplerotic phase, and before the function is restored after liver transplantation, the production of fibrinolytic inhibitors is reduced and the inactivation of fibrinogen activators is decreased, leading to an increase in fibrinogen activators, which stimulates protofibrin. The reduced viability of plasma fibrin inhibitors during hypothermic anesthesia also favors the development of protofibrillation. Severe liver disease is the most common cause of primary fibrinolysis. The levels of some fibrinolytic-related proteins, such as fibrinogen and α2AP, may be significantly reduced in severe liver disease, especially in the development of cirrhosis, probably due to impaired protein synthesis. In cirrhosis, impaired clearance results in increased plasma t-PA and u-PA levels and decreased PAI-1 levels. This may partially explain why enhanced fibrinolysis can occur in cirrhosis despite reduced fibrinogen. Amniotic fluid has strong procoagulant and pro-fibrinolytic activity, and bleeding with enhanced fibrinolysis as the main cause can occur in amniotic fluid embolism. The mechanism of primary fibrinolysis induced by extracorporeal circulation is unknown, but it may be due to activation of the fibrinolytic system by extracorporeal circulation equipment, abnormal vascular surfaces, and accelerated blood flow. In hypotension and shock from various causes, stagnant blood flow and tissue hypoxia can induce the release of t-PA from endothelial cells, which is also a possible cause of fibrinolysis.