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(Circulation. 2008;118:1408-1409.)
© 2008 American Heart Association, Inc.

Editorial

A Novel Role for Tissue-Type Plasminogen Activator

Prevention of Thromboembolic Occlusion

David J. Schneider, MD; Burton E. Sobel, MD

From the Cardiology Unit, Department of Medicine, Cardiovascular Research Institute, University of Vermont, Burlington.

Correspondence to David J. Schneider, MD, University of Vermont, 208 S Park Dr, Suite 2, Colchester, VT 05446. E-mail david.schneider@uvm.edu

Key Words: Editorials • embolism • stroke • thrombolysis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Activation of plasminogen by agents such as tissue-type plasminogen activator (tPA), yields plasmin, lyses fibrin, and thereby restores flow to blood vessels occluded by thrombi. Because tPA binds to fibrin, as does plasminogen, at low doses, tPA-mediated generation of plasmin is localized, rendering tPA clot selective. This result, plus its short half-life (4.5 minutes), led to the hope that its use would not only enhance coronary and cerebral thrombolysis but also reduce the risk of bleeding, including intracranial hemorrhage.¹ At high conventionally used doses, clot selectivity is incomplete. Perhaps that is why treatment with tPA compared with a non–clot-selective agent, streptokinase, reduced mortality in patients with ST-elevation myocardial infarction but did not diminish the incidence of intracranial hemorrhage.²

Article p 1442

In this issue of Circulation, Danielyan and colleagues describe a novel use of tPA, prevention rather than treatment of thrombi-occluding vessels resulting from emboli.³ Linkage of tPA to red blood cells (RBCs) prohibited its penetration into protective established thrombi, facilitated lysis of nascent thrombi induced by embolization of fibrin, and markedly prolonged the half-life of tPA in the circulation. Compared with soluble tPA, RBC-coupled tPA (RBC/tPA) more effectively lysed nascent cerebral thromboemboli and diminished hemorrhagic complications.

Nascent thrombi are lysed with particular efficacy by very low concentrations of tPA probably because cross-linking of fibrin is limited in such thrombi.⁴ Consistent with the observations of Danielyan et al, Fox and colleagues found that "subthrombolytic" concentrations of tPA prevented formation of an occlusive thrombi.⁴ In the Danielyan study, the prolonged . . . [Full Text of this Article]