Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation

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2016-01

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Abstract

Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.

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10.1586/17474086.2016.1135046

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Ghadimi, K, IJ Welsby, JH Levy and KE Dombrowski (2016). Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation. Expert review of hematology, 9(2). pp. 115–122. 10.1586/17474086.2016.1135046 Retrieved from https://hdl.handle.net/10161/29789.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Welsby

Ian James Welsby

Professor of Anesthesiology

As a practicing cardiothoracic anesthesiologist, I have contributed to the better understanding of the management and of perioperative thrombosis (particularly HIT). This has been as a Duke site PI for the Rare Thrombotic Diseases Consortium led by Dr T.L Ortel and a clinical collaborator with the basic and translational science approach to HIT led by Dr G Arepally. I have also championed novel approaches to dealing with perioperative HIT such as plasmaperesis.

Similarly, I have been a local leader in establishing management of transfusion approaches to major cardiac surgery including the novel introduction of autologous plateletpheresis to limit exposure to allogeneic platelet transfusions in this highly transfused population, identifying the transfusion requirements during thoracic aortic reconstruction and promoting use of a lower dose of rFVIIa use in this population, changing established clinical practice.

My research interests focus on perioperative transfusion and hematology concerns. Recently, Dr Kor (Mayo Clinic) and I received a multiple PI R-01 award to evaluate point-of-care/bedside washing of packed red blood cells to reduce perioperative lung injury. This novel repurposing of commonly available “cell-saver” technology is, for most surgical cases, the only practical means of delivering a washed product, and promises to be a critical advancement in perioperative transfusion medicine. I also have a longstanding interest in the rejuvenation of RBCs to normalize oxygen delivery capacity of transfused RBCs. Such a development will be of tremendous importance to transfusion practice, particularly for highly transfused populations and with current threats to blood banking inventory. 

In summary, I have dedicated my research career to improving the outcome of patients undergoing cardiothoracic surgery, understanding perioperative coagulopathy, and optimizing transfusion practice. 

Levy

Jerrold Henry Levy

Professor of Anesthesiology

Jerrold Levy is Professor of Anesthesiology, Critical Care, and Surgery (Cardiothoracic) at Duke University Medical Center in Durham, NC. He obtained his medical degree from the University of Miami, where he was an intern in internal medicine, and undertook his residency in the Department of Anesthesiology of the Massachusetts General Hospital and Harvard Medical School in Boston, where he was also Chief Resident, and completed fellowships in both Respiratory ICU and Cardiac Anesthesiology.  He previously was Professor, Deputy Chair for Research, and Chief of Cardiothoracic Anesthesiology at Emory University School of Medicine. His clinical and research interests include anticoagulation and its reversal, therapeutic strategies to prevent and treat coagulopathy and acute inflammatory responses in critically ill patients, clinical applications of recombinant and purified protein concentrates to treat bleeding, and pharmacologic approaches to treat shock.  He is currently Chair of the Subcommittee on Perioperative and Critical Care Thrombosis and Hemostasis for the International Society of Thrombosis and Hemostasis, Executive Editor of Anesthesiology, and consultant to the FDA‘s Biologic Products Advisory Committee.  He is the author of over 450 publications on PubMED, with over 100,000 citations on Google Scholar and a h-index of 95. He is also fluent in French and conversational in Spanish and Japanese.




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