Thrombolytic agents mechanisms

Qureshi, A.I., et al., Aggressive mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic agent for ischemic stroke a prospective study. Neurosurgery, 2002. 51(5) p. 1319-27 discussion 1327-9. 

The present investigations, although limited to the local application of fibrolase, demonstrate that under these conditions the enzyme lyses venous or arterial thrombi rapidly and with no observable systemic or hematologic side effects. In these thrombosis model systems the enzyme, either alone or in combination with antiplatelet therapy, offers a unique, safe, and specific mechanism for clot dissolution and may prove useful as a clinically effective alternative to, or for use in synergistic combination with, presently used thrombolytic agents. 

THROMBOLYTICS Secondary drug ANTIPLATELET AGENTS Effect Mechanism Precautions... 

Efforts to decrease the time until therapy was initiated to maximize both the rate of success of lytic therapy [fresher clots are more susceptible to lysis, especially with nonfibrin-specific agents (5)] and the impact of reperfusion on myocardial salvage led to a shift to intravenous administration of these drugs, which could be performed in the coronary care unit (CCU) or the emergency department (ED), saving 1-2 hours between diagnosis and the initiation of therapy. Trials performed with angiographic assessment after the initiation of thrombolytic therapy are patency studies infarct-related vessels found to be patent will include those that contained clot that was successfully dissolved by the therapy delivered, those that contained clot that resolved because of the body s own fibrinolytic mechanisms before therapy was instituted, and those that never had intracoronary thrombus as an occlusive event. 

The present results demonstrate that natural fibrolase exhibits effective in vivo thrombolytic activity in several animal thrombosis model systems. Infusion of the enzyme proximal to an occlusive thrombus induced rapid and specific thrombolysis in rabbit renal arterial and iliac venous thrombosis model systems. No evidence of hemorrhaging or alterations to the hemostatic system were observed in these studies. Additionally, no toxicity was observed and no angiographic, histologic, or functional evidence of side effects were obtained. The enzyme rapidly lysed 48 hr aged thrombi in the venous thrombosis model. This suggests that one of the primary mechanisms of thrombus resistance to PA-based agents. 

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