This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gurewich, V. Articles by Gent, M. Search for Related Content PubMed PubMed Citation Articles by Gurewich, V. Articles by Gent, M.

(Stroke. 1998;29:1255-1256.)
© 1998 American Heart Association, Inc.

Letters to the Editor

Intra-arterial Pro-urokinase in Ischemic Stroke

Victor Gurewich, MD, FACP

Jian-ning Liu, PhD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

To the Editor:

Dr del Zoppo et al are to be congratulated for successfully completing the first randomized, double-blind, controlled trial of intra-arterial pro-urokinase (pro-UK) in ischemic stroke (PROACT).¹ A sophisticated route of administration of pro-UK by microcatheter into the thrombus was chosen in order to maximize lysis and minimize hemorrhagic side effects. Moreover, at the low infusion rate (6 mg over 2 hours) that was used, there is no systemic conversion of pro-UK to urokinase, and its effect is entirely fibrin specific. As a result, little or no bleeding should have occurred, because in stroke, bleeding is correlated with nonspecificity (ie, streptokinase induces more bleeding than tPA).

In view of this prudent protocol, it is curious that intravenous heparin was given concomitantly with pro-UK in the treatment group or given alone in the placebo group.

Early anticoagulation with heparin for ischemic stroke has long been considered hazardous, and it has been recommended that heparin be delayed for at least 48 hours after embolism.² Even when heparin was administered by the subcutaneous route to patients with ischemic stroke, a 4-fold increase in hemorrhagic stroke was reported in the International Stroke Trial.³ Consequently, heparin has been scrupulously avoided in all of the clinical trials of tPA in stroke. Therefore, it is not surprising that in the PROACT study, a 15% incidence of intracranial bleeding occurred and more than a 3-fold increase in hemorrhagic stroke was observed when pro-UK was combined with a higher dose of heparin compared with a lower dose. . . . [Full Text of this Article]

Gregory J. del Zoppo, MD

The Scripps Research Institute

Randall T. Higashida, MD

University of California, San Francisco

Anthony J. Furlan, MD

The Cleveland Clinic Foundation

Howard A. Rowley, MD

University of California, San Francisco

Michael Gent, DSc

Hamilton Civic Hospitals Research Centre, and the PROACT Investigators

This article has been cited by other articles:

				A. Furlan, R. Higashida, L. Wechsler, M. Gent, H. Rowley, C. Kase, M. Pessin, A. Ahuja, F. Callahan, W. M. Clark, et al. Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial JAMA, December 1, 1999; 282(21): 2003 - 2011. [Abstract] [Full Text] [PDF]