Plasminogen Activators and Ischemic Stroke: Conditions for Acute Delivery

Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
Seminars in Thrombosis and Hemostasis (Impact Factor: 3.88). 03/2013; 39(4). DOI: 10.1055/s-0033-1338126
Source: PubMed


Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited.

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  • Seminars in Thrombosis and Hemostasis 06/2013; 39(4):327-328. DOI:10.1055/s-0033-1343616 · 3.88 Impact Factor
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    ABSTRACT: Great advances have been made in our understanding of the fibrinolytic system from the initial discovery of proteolysis of fibrin by plasmin to the multifaceted and complex role of the plasminogen-plasmin (P-P) system. We now know that the P-P system is composed of several serine proteases and their inhibitors (serpins). This system is involved in many physiological functions, including embryogenesis, cell migration, and wound healing. They also play an important role in the pathogenesis of many diseases, including atherosclerosis, obesity, cancer, and even autoimmune disorders, and neuronal degeneration. Knowledge of their role in cancer enables their use as a prognostic factor. Therapeutic use of various forms of proteases derived from this system has been employed as thrombolytic agents. In addition, small molecules designed to inhibit many of the components of the P-P system are now available for clinical trial, aimed at treatment of these various disorders. The history of such remarkable development of our knowledge on fibrinolysis is reviewed in this article.
    Seminars in Thrombosis and Hemostasis 07/2014; 40(5). DOI:10.1055/s-0034-1383545 · 3.88 Impact Factor