Fibrinolytic mechanism

Haemostasis is the mechanism activated after damage to the blood vessel wall that ensures that blood loss is restricted. Blood platelets are are activated and adhere to elements on the damaged lumenal surface of the vessel, eventually forming a platelet plug that stops the leakage of blood. Fibrinolytic mechanisms later produce lysis of the platelet mass when repair of the vessel has occurred. 

Regulation of the fibrinolytic system is useful in therapeutics. Increased fibrinolysis is effective therapy for thrombotic disease. Tissue plasminogen activator, urokinase, and streptokinase all activate the fibrinolytic system (Figure 34-3). Conversely, decreased fibrinolysis protects clots from lysis and reduces the bleeding of hemostatic failure. Aminocaproic acid is a clinically useful inhibitor of fibrinolysis. Heparin and the oral anticoagulant drugs do not affect the fibrinolytic mechanism. 

The inflammatory process in sepsis is also directly linked to the coagulation system. Proinflammatory mechanisms that promote sepsis are also procoagulant and antiflbrinolytic, whereas fibrinolytic mechanisms may be anti-inflammatory. A key endogenous substance involved in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Levels of protein C are reduced in patients with sepsis. ... 

Vison, J. A., Teufel, K., and Wu, N. 2004. Green and black teas inhibit atherosclerosis by lipid, anti-oxidant, and fibrinolytic mechanisms. J. Agric. Food Chem. 52 3661-65. 

When a blood clot is mobilized, it is called a thrombus or embolus. It moves through blood vessels eventually causing a blockage—called a thromboembolism—resulting in decreased blood flow (ischemia) that causes death (necrosis) of tissues in the effected area. Thromboembolisms disintegrate naturally in about two weeks through the fibrinolytic mechanism, which breaks down fibrin. 

Efforts to decrease the time until therapy was initiated to maximize both the rate of success of lytic therapy [fresher clots are more susceptible to lysis, especially with nonfibrin-specific agents (5)] and the impact of reperfusion on myocardial salvage led to a shift to intravenous administration of these drugs, which could be performed in the coronary care unit (CCU) or the emergency department (ED), saving 1-2 hours between diagnosis and the initiation of therapy. Trials performed with angiographic assessment after the initiation of thrombolytic therapy are patency studies infarct-related vessels found to be patent will include those that contained clot that was successfully dissolved by the therapy delivered, those that contained clot that resolved because of the body s own fibrinolytic mechanisms before therapy was instituted, and those that never had intracoronary thrombus as an occlusive event. 

This approach is based on the fact that fibrin forms the frame- rork or structural support of a clot. Dissolution of the fibrin should result in lysis of the clot with restoration of blood flow. The significance of fibrinolysis the mtential of thrombolysis in treatment of thrombotic coronary occlusion and fibrinolytic mechanisms have been reviewed. 

Coagulation summarizes the mechanisms involved in stopping bleeding due to an injured or defective vessel wall. Coagulation is characterized by procoagulatory and anticoagulatory factors that are in balance under normal conditions. Vessel injuries are occluded by the coagulation system and spontaneous vessel occlusions dissolved by the fibrinolytic cascade. 

Mor, A. Maillard, J. Favreau, C. Reboud-Ravaux, M. Reaction of thrombin and proteinases of the fibrinolytic system with a mechanism-based inhibitor, 3,4-dihydro-3-benzyl-6-chloromethyl-coumarin. Biochim. Biophys. Acta 1990, 1038, 158-163. 

Proinflammatory mechanisms in sepsis are also procoagulant and antifibrinolytic. Levels of activated protein C, a fibrinolytic and antiinflammatory substance, are decreased in sepsis. 

Mechanism of Action A tissue plasminogen activator that activates the fibrinolytic system by directly cleaving plasminogen to generate plasmin, an enzyme that degrades the fibrin ot the thrombus. Therapeutic Effect Exerts CV-thrombolytic action. Pharmacokinetics Rapidlycleared from plasma. Eliminated primarilyby the liverand kidney. Haif-Hfe 13-16 min. 

Mechanism of Action An enzyme that activates the fibrinolytic system by converting plasminogen to plasmin, an enzyme that degrades fibrin clots. Acts indirectlybyform ing a complex with plasminogen, which converts plasminogen to plasmin. Action oc-curs within the thrombus, on its surface, and in circulating blood. Therapeutic Effect Destroys thrombi. 

As well as their core intracellular activities, many annexins have evolved other, specialised extracellular functions, such as the immunomodulatory action of annexin 1 or the pro-fibrinolytic activity of annexin 2. In this guise they contribute to homeostasis and repair regulating and resolving infection and trauma, and will doubtless prove to be involved in many pathological processes. In the case of autoimmunity, when these mechanisms become disturbed, annexins are again implicated (for example in APL, SLE and diabetes) which underscores their importance as key regulatory factors. 

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