Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications

Sina Rashedi; Christie M. Greason; Parham Sadeghipour; Azita H. Talasaz; Michelle L. O'Donoghue; David Jimenez; Manuel Monreal; Christopher D. Anderson; Mitchell S. V. Elkind; Lisa M. Baumann Kreuziger; Irene M. Lang; Samuel Z. Goldhaber; Stavros V. Konstantinides; Gregory Piazza; Harlan M. Krumholz; Eugene Braunwald; Behnood Bikdeli

doi:10.1055/s-0044-1781451

Seminars in Thrombosis and Hemostasis, Table of Contents

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

¹Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

,

Christie M. Greason

²Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

,

Parham Sadeghipour

¹Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

³Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran

,

Azita H. Talasaz

⁴Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, Virginia

⁵Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, New York

⁶Department of Pharmacy, New York-Presbyterian Hospital Columbia University Medical Center, New York, New York

,

Michelle L. O'Donoghue

⁷Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

,

David Jimenez

⁸Respiratory Department, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain

⁹Medicine Department, Universidad de Alcalá (IRYCIS), Madrid, Spain

¹⁰CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain

,

Manuel Monreal

¹¹Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Spain

¹²Universidad Catolica de Murcia, Murcia, Spain

,

Christopher D. Anderson

¹³Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Boston, Massachusetts

¹⁴McCance Center for Brain Health, Massachusetts General Hospital, Boston, Massachusetts

¹⁵Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts

,

Mitchell S. V. Elkind

¹⁶Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

¹⁷Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York

,

Lisa M. Baumann Kreuziger

¹⁸Medical College of Wisconsin, Milwaukee, Wisconsin

¹⁹Blood Research Institute, Versiti, Milwaukee, Wisconsin

,

Irene M. Lang

²⁰Department of Internal Medicine II, Cardiology and Center of Cardiovascular Medicine, Medical University of Vienna, Vienna, Austria

,

Samuel Z. Goldhaber

²Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²¹Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

,

Stavros V. Konstantinides

²²Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

²³Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece

,

Gregory Piazza

²Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²¹Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

,

Harlan M. Krumholz

²⁴YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut

²⁵Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut

²⁶Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut

,

Eugene Braunwald

⁷Division of Cardiovascular Medicine, TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²¹Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

,

Behnood Bikdeli

²Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²¹Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²⁴YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut

› Author Affiliations

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

Full Text

References

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