Fibrinolytic agents

The action of therapeutric fibrinolytic agents is summarized in Fig 1.

Fig. 1 Action of therapeutic fibrinolytic agents: t-PA, tissue plasminogen activator; PAI, plasminogen activator inhibitor; scu-PA, single-chain urinary plasminogen inhibitor; tcu-PA, two-chain urinary plasminogen inhibitor; EACA, e-aminocaproic acid.

Streptokinase

Streptokinase, a single-chain polypeptide enzyme derived from b-hemolytic streptococcal cultures, binds to circulating plasminogen in a ratio of 1:1, causing molecular-conformational changes that lead to exposure of plasminogen's active site resulting in partial plasminogen conversion to plasmin. The streptokinase-plasminogen complex, which is not blocked by a2-antiplasmin, is subsequently converted to streptokinase-plasmin complex which rapidly activates plasminogen to plasmin. Streptokinase-plasmin activity is not fibrin specific, but can also attack fibrinogen and other procoagulants. The half-life of the streptokinase-plasminogen complex is about 23 min; it is inactivated, in part, by antistreptococcal antibodies. Streptokinase decreases plasma fibrinogen levels for 24 to 36 h and the fibrinolytic effect resolves within a few hours; however, a prolonged thrombin time may persist for up to 24 h because of the decrease in fibrinogen levels and the presence of circulating fibrinogen degradation products. Circulating antistreptokinase antibody may be stimulated by recent streptococcal infection and a higher dose may be needed to ensure antibody neutralization. Treatment with strepokinase would be unlikely to induce an effective thrombolytic state when antibody titers are high, as may be seen within 2 years of therapeutic use.

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