Streptase, Streptokinase, acts with plasminogen to produce an "activator complex" that converts plasminogen to the proteolytic enzyme plasmin. The t _½ of the activator complex is about 23 minutes; the complex is inactivated, in part, by antistreptococcal antibodies. The mechanism by which dissociated streptokinase is eliminated is clearance by sites in the liver; however, no metabolites of streptokinase have been identified. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Plasmin is inactivated by circulating inhibitors, such as (alpha)-2-plasmin inhibitor or (alpha)-2-macroglobulin. These inhibitors are rapidly consumed at high doses of streptokinase.

Intravenous infusion of Streptokinase is followed by increased fibrinolytic activity, which decreases plasma fibrinogen levels for 24 to 36 hours. The decrease in plasma fibrinogen is associated with decreases in plasma and blood viscosity and red blood cell aggregation. The hyperfibrinolytic effect disappears within a few hours after discontinuation, but a prolonged thrombin time may persist for up to 24 hours due to the decrease in plasma levels of fibrinogen and an increase in the amount of circulating fibrin(ogen) degradation products (FDP). Depending upon the dosage and duration of infusion of Streptokinase, the thrombin time will decrease to less than two times the normal control value within 4 hours, and return to normal by 24 hours.

Intravenous administration has been shown to reduce blood pressure and total peripheral resistance with a corresponding reduction in cardiac afterload. These expected responses were not studied with the intracoronary administration of Streptase, Streptokinase. The quantitative benefit has not been evaluated.

Variable amounts of circulating antistreptokinase antibody are present in individuals as a result of recent streptococcal infections. The recommended dosage schedule usually obviates the need for antibody titration.

Two very large, randomized, placebo-controlled studies ^(1,2) involving almost 30,000 patients have demonstrated that a 60-minute intravenous infusion of 1,500,000 IU of Streptokinase significantly reduces mortality following a myocardial infarction. One of these studies also evaluated concomitant oral administration of low dose aspirin (160 mg/d over one month).

In the GISSI study the reduction in mortality was time dependent. There was a 47% reduction in mortality among patients treated within one hour of the onset of chest pain, a 23% reduction among patients treated within three hours, and a 17% reduction among patients treated between three and six hours. There was also a reduction in mortality in patients treated between six and twelve hours from the onset of symptoms, but the reduction was not statistically significant.

In the ISIS-2 study the reduction in mortality was also time dependent. If Streptokinase and aspirin were administered within the first hour after symptom onset, the reduction in mortality was 44%. The reduction in the odds of death in patients treated within four hours was 53% for the combination of Streptokinase and aspirin, and 35% for Streptokinase alone. However, the reduction was still significant when treatment was started 5-24 hours after symptom onset: 33% for the combined therapy and 17% for Streptokinase alone. Overall, in the 0-24 hour time period there was a 42% reduction in the odds of death with combined treatment (Streptokinase and aspirin) versus placebo (2p<0.00001) and a 25% reduction in the odds of death with Streptokinase alone versus placebo (2p<0.00001).

Bookmark this page: