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Semin Thromb Hemost 2024; 50(05): 773-789
DOI: 10.1055/s-0044-1781451
Review Article

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications

Sina Rashedi
1   Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Christie M. Greason
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Parham Sadeghipour
1   Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
3   Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Azita H. Talasaz
4   Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, Virginia
5   Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, New York
6   Department of Pharmacy, New York-Presbyterian Hospital Columbia University Medical Center, New York, New York
,
Michelle L. O'Donoghue
7   Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
David Jimenez
8   Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
9   Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain
10   CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain
,
Manuel Monreal
11   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Spain
12   Universidad Catolica de Murcia, Murcia, Spain
,
Christopher D. Anderson
13   Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Boston, Massachusetts
14   McCance Center for Brain Health, Massachusetts General Hospital, Boston, Massachusetts
15   Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
,
Mitchell S. V. Elkind
16   Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York
17   Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
,
Lisa M. Baumann Kreuziger
18   Medical College of Wisconsin, Milwaukee, Wisconsin
19   Blood Research Institute, Versiti, Milwaukee, Wisconsin
,
Irene M. Lang
20   Department of Internal Medicine II, Cardiology and Center of Cardiovascular Medicine, Medical University of Vienna, Vienna, Austria
,
Samuel Z. Goldhaber
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Stavros V. Konstantinides
22   Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
23   Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece
,
Gregory Piazza
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Harlan M. Krumholz
24   YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut
25   Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
26   Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
,
Eugene Braunwald
7   Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Behnood Bikdeli
2   Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
21   Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
24   YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut
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Abstract

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Keywords

fibrinolytic agents - plasminogen activator - thromboembolism


Publication History

Article published online:
01 March 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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