Plasminogen fibrin

The high affinity LBS is involved in the interaction of plasminogen with fibrin, a2-antiplasmin, and a plasmin inhibitor called histidine-rich glycoprotein. It has been observed that plasminogen activation takes place on the surface of fibrin and that a2-antiplasmin competitively inhibits the plasminogen—fibrin interaction at the high affinity LBS. 

Fibrinolytics. Figure 3 Plasminogen activation (a) Kinetics of plasminogen activation by uPA (urokinase-type) and tPA (tissue-type) plasminogen activators. Effect of fibrin (b) Ternary complex formation between enzyme (tPA), substrate (Pg) and cofactor (F) Abbreviations plasmin (P), fibrin (F), plasminogen (Pg). Plasmin, formed in time, is expressed in arbitrary units. 

Since plasmin in free form (not bound to fibrin) is extremely and rapidly inactivated by the inhibitor system (Fig. 4), plasminogen activators are used for treatment of thrombosis. Under such a condition, if plasmin is formed by the activators (especially by tPA) at the site of fibrin, the bound form can degrade fibrin because it is protected against the inhibitor system. In the medical practice, mainly two endogenous plasminogen activators, tPA and uPA, and one exogenous, the streptokinase (SK) are used [1,4]. 

Summarizing the fibrinolytic therapy, it should be emphasized that efficient treatment needs urgent application of plasminogen activator (within a few hours) to prevent the formation of crosslinks in the fibrin structure (Fig. 2) and to find the localization of thrombus to emerge plasmin on the surface of fibrin to prevent rapid inactivation of the enzyme by the inhibitor system of fibrinolysis (Fig. 3). 

Plasmin, a serine protease (83 kDa), can degrade fibrin, and its degradation products (FDP) are soluble in the blood. Plasmin is formed from its proenzyme (zymogen, precursor), plasminogen (92 kDa), synthesized by the liver, and secreted into the blood circulation, where its concentration is 2 pM. Plasminogen is converted to plasmin by plasminogen activators (serine proteases). 

Although the exact action of the thrombolytic dragp is slightly different, these drugs break down fibrin clots by converting plasminogen to plasmin (fibrinolysin). Plasmin is an enzyme that breaks down the fibrin of a blood clot. This reopens blood vessels after their occlusion and prevents tissue necrosis. 

Inhibits platelet aggregation by increasing levels of cAMP Binds protein C, which is then cleaved by thrombin to yield activated protein C this in combination with protein S degrades factors Va and Villa, limiting their actions Activates plasminogen to plas-min, which digests fibrin the action of t-PA is opposed by plasminogen activator inhibitor- (PAI-1)... 

Fibrin is dissolved by plasmin. Plasmin exists as an inactive precursor, plasminogen, which can be activated by tissue plasminogen activator (t-PA). Both t-PA and streptokinase are widely used to treat early thrombosis in the coronary arteries. 

Fibrinolysins are produced by both staphylococci (staphylokinase) and streptococci (streptokinase). These toxins dissolve fibrin clots, formed by the host around wounds and lesions to seal them, by indirect activation of plasminogen, thereby increasing the likelihood of organism spread. Streptokinase m be employed elinieally in conjunction with streptodomase (Chapter 25) in the treatment of thrombosis. 

This drug is more potent and more selective for fibrin-bound plasminogen than any other known plasminogen activator. Unlike t-PA, desmoteplase is not activated by fibrinogen or (3-amyloid proteins, factors that may exacerbate the risk for ICH. Moreover, desmoteplase inhibits t-PA-induced potentiation of excitotoxic injury. The effect of IV administration of desmoteplase 3-9 hours after symptom onset in stroke patients who demonstrate a mismatch on PWI/DWI MRI is currently being investigated. ... 

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

The lysine binding sites on free Lys-plasminogen or free Lys-plasmin are susceptible to inhibition by a2 plasmin, the primary inhibitor of plasmin, because these sites are not protected by interaction with fibrin. However, when Lys-plasminogen is tightly bound to the fragment E domain, it is rapidly activated by the... 

The fibrinolytic activity of scu-PA is more efficient than that of either LMW-UK or HMW-UK. Apparently, fibrin within a clot neutralizes an inhibitor in plasma that normally hinders binding of scu-PA to plasminogen, thereby facilitating binding of scu-PA to Glu-plasminogen and its resultant activation (37, 38). A cell surface receptor for scu-PA has been implicated in the activation of plasminogen and the internalization and degradation of u-PA complexed to inhibitors (39). 

Tissue plasminogen activator activates plasmin to dissolve the fibrin continuously made at low levels. 

UK is a serine protease that activates plasminogen to plasmin. Plasmin dissolves the fibrin in blood clots. The attachment of UK to the islet surface was expected to dissolve blood clots that surrounded the islets in the liver thus, IBMIR could be inhibited in the initial stages. A fibrin plate-based assay was performed to assess the... 

The answer is c. (Katzung, pp 572—574.) Alteplase is an unmodified tPA. Alteplase activates plasminogen that is bound to fibrin. The plasmin... 

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