Plasminogen streptokinase action

Anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC), is the plasminogen-streptokinase complex (above) in which the enzyme centre that converts plasminogen to plasmin is protected from deactivation, so prolonging its action. 

Tissue Plasminogen Aetivator (tPA). While streptokinase and urokinase can effectively induce clot dissolution in the majority of patients if given early, they lack clot specificity. Treatment with these enzymes results in a systemic lytic state attributable to their degradative action on circulating fibrinogen. Tissue plasminogen activator (tPA) was developed to achieve rapid and specific thrombolysis. 

Figure 51-7. Scheme of sites of action of streptokinase, tissue plasminogen activator (t-PA), urokinase, plasminogen activator inhibitor, and Kj-antiplasmin (the last two proteins exert inhibitory actions). Streptokinase forms a complex with plasminogen, which exhibits proteolytic activity this cleaves some plasminogen to plasmin, initiating fibrinolysis. 

Mammahan blood will clot spontaneously if allowed to stand however, on further standing, this clot may dissolve as a result of the action of a proteolytic enzyme called plasmin. Plasmin is normally present as its inactive precnrsor, plasminogen. Certain strains of streptococci were fonnd to produce a substance which was capable of activating plasminogen (Fig. 25.3), a phenomenon that suggested a potential use in liquefying clots. This snbstance was isolated, found to be an enzyme and called streptokinase. 

UK is nonantigenic and its mechanism of action is much more direct compared with that of streptokinase. UK cleaves plasminogen, by first-order reaction kinetics, to form plasmin. It is pH and temperature stable. The lack of circulating neutralizing antibodies and its direct mechanism of action allow for a predictable dose response relationship. 

Urokinase is an endogenous plasminogen activator that occurs in different organs. Urokinase used therapeutically is obtained from human cultured kidney cells. Circulating antibodies are not expected. The substance is more expensive than streptokinase and also does not depend on fibrin in its action. 

F. 45.7. Regulation of plasmin activation. Plasminogen can be activated by either t-PA or scu-PA (+). PAI-1 blocks t-PA action (-). Streptokinase binding to plasminogen allows autocatalysis to form plasmin. Circulating a2-antiplasmin blocks (—) the activity of any soluble plasmin that may be in the blood. 

Anistreplase Prodrug streptokinase plus recombinant human plasminogen 1-2 hours Slowly releases streptokinase-activated plasminogen single bolus administration provides bng duration of action... 

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