Pre-clinical studies of plasmin: superior benefit-to-risk ratio of plasmin compared to tissue plasminogen activator.

Thrombosis Research
Victor J Marder

Abstract

Currently-used thrombolytic agents are plasminogen activators (PA). While effective for treating thrombotic disease, PA use is associated with unavoidable hemorrhagic complications in susceptible individuals. Thus, there is an urgent need for new agents or approaches that provide greater hemostatic safety without sacrificing thrombolytic efficacy. Evidence now strongly indicates that 'direct-acting' thrombolytics, which do not require conversion of the precursor plasminogen to the active form plasmin, offer such a potential. The biochemical properties of plasmin provide a theoretical foundation for safe and effective therapy, based on thrombolytic efficacy upon local catheter delivery of agent and neutralization of circulating agent by its inhibitor (alpha-2 antiplasmin) to prevent bleeding complications. In vitro and animal studies support these predictions. In comparison with tissue-plasminogen activator (t-PA), plasmin shows a distinct benefit-to-risk advantage. First, plasmin is equally effective as t-PA in thrombolysis and may be superior for treating thrombi in totally-occluded vessels. Second, whereas t-PA causes bleeding from vascular trauma sites in animals when infused at dosages used for thrombolysis (0.5-1 mg/kg), p...Continue Reading

References

Mar 15, 2008·Stroke; a Journal of Cerebral Circulation·Reza JahanVictor J Marder
Jul 20, 1945·The Journal of General Physiology·L R Christensen, C M Macleod

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Citations

Oct 17, 2009·Journal of Thrombosis and Thrombolysis·Christophe DommkePeter Verhamme
Oct 12, 2010·Stroke; a Journal of Cerebral Circulation·Victor J MarderVik Arora
Mar 19, 2013·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Hideki MotoyamaHiroshi Date
Jun 16, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Cen ChenZhi-Ning Xia
Oct 30, 2016·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Peter J MitchellUNKNOWN Plasmin Trial Investigators
Feb 6, 2017·Journal of the American Heart Association·Thomas BonnardChristoph Eugen Hagemeyer
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·V J Marder
Dec 1, 2009·Journal of Thrombosis and Haemostasis : JTH·V J Marder, V Novokhatny
Sep 23, 2020·Pharmacology & Therapeutics·Li ZhangGuanhua Du

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