Thrombomodulin in disseminated intravascular coagulation and other critical conditions-a multi-faceted anticoagulant protein with therapeutic potential.
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2019-08-15
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Abstract
Thrombomodulin plays a vital role in maintaining intravascular patency due to its anticoagulant, antiinflammatory, and cytoprotective properties. However, under pathological conditions such as sepsis and systemic inflammation, endothelial thrombomodulin expression is downregulated and its function impaired. As a result, administering thrombomodulin represents a potential therapeutic modality. Recently, the effect of recombinant thrombomodulin administration in sepsis-induced coagulopathy was evaluated in a randomized controlled study (SCARLET). A 2.6% 28-day absolute mortality reduction (26.8% vs. 29.4%) was reported in 800 patients studied that was not statistically significant; however, a post hoc analysis revealed a 5.4% absolute mortality reduction among the patients who fulfilled the entry criterion at baseline. The risk of bleeding did not increase compared to placebo control. Favorable effects of thrombomodulin administration have been reported not only in sepsis-induced coagulopathy but also in disseminated intravascular coagulations with various backgrounds. Interestingly, beneficial effects of recombinant thrombomodulin in respiratory, renal, and cardiovascular diseases might depend on its anti-inflammatory mechanisms. In this review, we summarize the accumulated knowledge of endogenous as well as recombinant thrombomodulin from basic to clinical aspects and suggest future directions for this novel therapeutic agent.
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Ito, Takashi, Jecko Thachil, Hidesaku Asakura, Jerrold H Levy and Toshiaki Iba (2019). Thrombomodulin in disseminated intravascular coagulation and other critical conditions-a multi-faceted anticoagulant protein with therapeutic potential. Critical care (London, England), 23(1). p. 280. 10.1186/s13054-019-2552-0 Retrieved from https://hdl.handle.net/10161/19264.
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Jerrold Henry Levy
Jerrold H Levy, MD, FAHA, FCCM, is Professor of Surgery (Cardiothoracic) and Professor Emeritus of Anesthesiology/Critical Care at Duke University Medical Center in Durham, NC. He is also an Adjunct Professor in theDepartment of Pathology and Laboratory Medicine and the Centre for Blood Research at the University of British Columbia. Currently, he serves as Vice Chair of the Scientific and Standardization Committees of the International Society of Thrombosis and Hemostasis and previously served as Chair of the Perioperative and Critical Care Committee. He obtained his medical degree from the University of Miami, where he was a resident in internal medicine, followed by an Anesthesiology residency at the Massachusetts General Hospital/Harvard Medical School, where he was Chief Resident, and completed fellowships in Respiratory Intensive Care and Cardiac Anesthesiology. Before Duke, he was Professor and Deputy Chair for Research at Emory University School of Medicine. Dr Levy is currently an Associate Editor for the Journal of Thrombosis and Haemostasis, an Editor for the European Heart Journal: Cardiovascular Pharmacology, and on the Editorial Board for the Journal of Thoracic and Cardiovascular Surgery, and previously served as an Executive Editor for Anesthesiology. His current clinical and research interests include anticoagulation and its reversal, therapeutic strategies to prevent and treat coagulopathy and acute inflammation in critically ill patients and extracorporeal life support, applications of recombinant and purified protein concentrates for treating bleeding and inflammation, and therapeutic approaches to anaphylaxis. He is the author of over 600 publications on PubMed, with over 100,000 citations, an h-index of 112, and an i10-index of 500. He is also fluent in French and conversational in Spanish and Japanese.
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