Plasma Streptokinase

Streptokinase has an initial plasma half-life (/ 2 of 18 min, and a P half-life of 83 min (73) it is well recognized that the thrombolytic efficacy of the enzyme decreases as the age of the thrombus increases thus, thrombolysis is significantly decreased when therapy is initiated more than three hours after an occlusion (74). 

An enzyme obtained from human plasma by conversion of profibrinolysin with streptokinase to fibrinolysin. Proteolytic enzyme of unknown structure molar mass = 75000. 

Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin. Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within. 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Streptokinase (44-45 u) added to the plasma without rinsing after the curve leveled off. 

Streptokinase, anistreplase and urokinase are not well absorbed by fibrin thrombi and are called nonfibrin-selective. They convert plasminogen to plasmin in the circulation, which depletes plasma fibrinogen and induces a general hypocoagulant state. This does not reduce their local thrombolytic potential but increases the risk of bleeding. 

Anisoylatedplasminogen streptokinase activator complex (APSAC)(Table 11-4) is an anisoyl (p-methoxybenzoyl) derivative of the active (lysine) site of the plasminogen component of this complex. Acylation inactivates the enzyme but does not decrease the affinity of the complex for fibrin. The resultant slow deacylation (tU2 = 40 min) should achieve relative selectivity for the fibrin in the clot over circulating plasma fibrinogen. Hydrolysis of anisoyl amide following binding onto the thrombus (i.e., activation) leads to fibrinolysis. APSAC has been reported to produce a 60-80% reperfusion rate following IV administration. 

A loading dose of streptokinase (250,000 U 2.5 mg) must be given intravenously to overcome plasma antibodies that are directed against the protein. These inactivating antibodies result from prior streptococcal infections. The... 

Human tissue plasminogen activator, purified, glycosylated, 527 residues purified from CHO cells. Eminase is a lyophilized formulation of anistreplase, the p-anisoyl derivative of the primary Lys-plasminogen-streptokinase activator complex (a complex of Lys-plasminogen and streptokinase). A p-anisoyl group is chemically conjugated to a complex of bacterial-derived streptokinase and human plasma-derived Lys-plasminogen proteins. 

Figure 6.9 Urinary, 2,3-dinor-thromboxane (Tx) B2 and plasma 11-dehydro-thromboxane B2 (inset) following administration of streptokinase (SK), 750 000—1 500 000 units intravenously, in patients with acute myocardial infarction. The shaded area represents the range of urinary 2,3-dinor-thromboxane B2 levels observed in patients with acute myocardial infarction not receiving thrombolytic therapy n = 12). The solid area on the y-axis is the range in healthy volunteers. Ml, myocardial infarction not receiving thrombolytic therapy...

Figure 6.10 Effect of streptokinase (SK) on fibrinogen concentration and platelet aggregation induced by ADP in platelet-rich plasma. Platelets were incubated with streptokinase for 1 minute prior to the addition of ADP, lfimo L and aggregation monitored by light transmission. Samples for fibrinogen were collected in aprotinin to prevent continued lysis. The fibrinogenolytic and proaggregatory effects of streptokinase were concentration dependent and were inhibited by aprotinin and e-aminocaproic acid (e-ACA)...

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