Читать книгу Practical Cardiovascular Medicine - Elias B. Hanna - Страница 107

Fibrinolytics bind to the clot-bound plasminogen and convert it to plasmin, which promotes the degradation of fibrin (Figure 2.3). The old fibrinolytic streptokinase also binds to free plasminogen; thus, in addition to lysing fibrin, it depletes systemic, free fibrinogen and affects systemic coagulation for 12–24 hours.

Alteplase (recombinant tissue plasminogen activator [r-tPA]) binds to the plasminogen entrapped in a thrombus and thus mainly degrades fibrin of a thrombus, rather than systemic fibrinogen (fibrin-specific fibrinolytic). Being more concentrated at the thrombus level, it is a more effective lytic than streptokinase. It generally does not affect the systemic fibrinogen and has a short half-life of only 6 minutes; thus, after the infusion is discontinued and the drug eliminated (~30 min), there is no significant residual effect on systemic coagulation. Therefore, the performance of PCI soon after r-tPA administration is not necessarily associated with a significant increase in bleeding. On the other hand, this short half-life and the lack of residual effect on the systemic coagulation explain the high risk of recurrent thrombosis and the need to start heparin infusion immediately at the end of r-tPA infusion in MI.

In the GUSTO trial of r-tPA vs. streptokinase, r-tPA further reduced mortality by 1% and reduced major bleeding in general, but increased intracranial hemorrhage by 0.25% in comparison with streptokinase.²¹

Reteplase (r-PA) is a mutation variant of r-tPA. It is slightly less fibrin-specific than r-tPA and has a longer half-life (~15 min), allowing its administration in two boluses rather than an infusion. It has the same mortality benefit and bleeding risk as r-tPA.

Tenecteplase (TNK) is also a mutation variant of r-tPA that is 14 times more fibrin-specific than r-tPA and less likely to be degraded by tPA inhibitors. Thus, TNK is slightly more effective, which explains the higher TIMI 3 flow rate achieved with TNK vs. r-tPA (~65% vs. 60%). It also has a longer half-life than r-tPA, with a duration of effect of ~120 minutes. In the ASSENT-2 trial, TNK was associated with the same overall mortality as r-tPA, but a reduction in major non-cerebral bleeding and a reduction in mortality of patients presenting >4 hours after symptom onset.²⁵