Thrombosis Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Guest Editors: Christian Doutremepuich, Jawad fareed, Jeanine M. Walenga, Jean-Marc Orgogozo, and Marie Lordkipanidzé Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Thrombosis Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Guest Editors: Christian Doutremepuich, Jawad fareed, Jeanine M. Walenga, Jean-Marc Orgogozo, and Marie Lordkipanidze´ Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Thrombosis.” All articles are open access articles distributed under the Creative Commons Attribu- tion License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Louis M. Aledort, USA Thomas Kickler, USA Johannes Oldenburg, Germany David Bergqvist, Sweden S. P. Kunapuli, USA Graham F. Pineo, Canada Francis J. Castellino, USA Jose A. Lopez, USA Domenico Prisco, Italy M. Cattaneo, Italy C. A. Ludlam, Uk Karin Przyklenk, USA Beng Hock Chong, Australia Nageswara Madamanchi, USA Ashwini Koneti Rao, USA Frank C. Church, USA Martyn Mahaut-Smith, UK F. R. Rickles, USA Giovanni de Gaetano, Italy P. M . Ma nnu cc i, Ita ly Evqueni Saenko, USA David H. Farrell, USA Osamu Matsuo, Japan Paolo Simioni, Italy Alessandro Gringeri, Italy Keith R. McCrae, USA C. Arnold Spek, The Netherlands Jolan´ Harsfalvi,´ Hungary Paulette S. Mehta, USA Perumal Thiagarajan, USA Debra A. Hoppensteadt, USA Joost Meijers, The Netherlands Cees Vermeer, The Netherlands Omer Iqbal, USA Edith Nutescu, USA Ted Wun, USA Contents Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin, Christian Doutremepuich Volume 2012, Article ID 626289, 1 page Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations, GunduH.R.RaoandJawadFareed Volume 2012, Article ID 104707, 9 pages The Role of Dermcidin Isoform 2: A Two-Faceted Atherosclerotic Risk Factor for Coronary Artery Disease and the Effect of Acetyl Salicylic Acid on It, Rajeshwary Ghosh, Uttam K. Maji, Rabindra Bhattacharya, and Asru K. Sinha Volume 2012, Article ID 987932, 9 pages Paradoxical Effect of Aspirin, Christian Doutremepuich, Omar Aguejouf, Vanessa Desplat, and Francisco X. Eizayaga Volume 2012, Article ID 676237, 4 pages Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms, Bianca Rocca and Giovanna Petrucci Volume 2012, Article ID 376721, 11 pages Clinical Use of Aspirin in Treatment and Prevention of Cardiovascular Disease, Yuxiang Dai and Junbo Ge Volume 2012, Article ID 245037, 7 pages Thrombotic Events Associated to Aspirin Therapy, Christian Doutremepuich, Omar Aguejouf, Vanessa Desplat, Dominique Duprat, and Francisco X. Eizayaga Volume 2012, Article ID 247363, 5 pages Aspirin: Pharmacology and Clinical Applications, Enma V. Paez Espinosa, John P. Murad, and Fadi T. Khasawneh Volume 2012, Article ID 173124, 15 pages Beneficial Effect of Ultra-Low-Dose Aspirin in Platelet Activity Alterations and Haemorrhage Observed in Experimental Portal Hypertension, F. X. Eizayaga, O. Aguejouf, V. Desplat, and C. Doutremepuich Volume 2012, Article ID 430460, 6 pages Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?, Wolfgang Losche,¨ Janina Boettel, Bjorn¨ Kabisch, Johannes Winning, Ralf A. Claus, and Michael Bauer Volume 2012, Article ID 720254, 8 pages Hindawi Publishing Corporation Thrombosis Volume 2012, Article ID 626289, 1 page doi:10.1155/2012/626289 Editorial Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Christian Doutremepuich Laboratoire d’H´ematologie, Universit´e Victor Segalen Bordeaux 2, 146 Rue L´eoSaignat, 33076 Bordeaux Cedex, France Correspondence should be addressed to Christian Doutremepuich, [email protected] Received 1 July 2012; Accepted 1 July 2012 Copyright © 2012 Christian Doutremepuich. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acetyl salicylic acid or aspirin is one of the most famous The work of Losche¨ et al. (Jena University Hospital, Jena, drugs in the world. Aspirin has been increasingly used for Germany) on the problem of the reduction of mortality in prevention of cardiovascular events and is, particularly in critically ill patients also demonstrates the effectiveness of recent decades, the most used nonsteroidal anti-inflam- antiplatelet drugs to prevent organ failure. matory drug. The three experimental studies from the laboratory of Thus, it was necessary to have several contributions to Doutremepuich concern the paradoxical action of aspirin precise the interest and the side effects of aspirin in cardiol- used at different dosages. These different effects can explain ogy, pharmacology, and neurology. the thrombosis observed in clinical practice after aspirin A general review on aspirin pharmacology was made discontinuation. The question could be also: what is the by Espinosa et al. (Western University of Health Sciences, effect of a drug at ultralow dose? Pomona, CA, USA). This review article helps to understand In conclusion, this special issue can represent a “state of the role of platelets in primary hemostasis and atherothrom- art” on aspirin and thrombosis with new hypotheses of work. bosis, the use of aspirin in the prevention, and treatment of cardiovascular diseases. Acknowledgments In the review article by B. Rocca and G. Petrucci (Catholic University School of Medicine, Rome, Italy), they have Thanks are due to Professors J. Fareed, J. M. Walenga, J.- detailed the phenomenon of variability in the responsiveness M. Orgogozo, and M. Lordkipanidze´ for their valuable to low-dose aspirin and reported the explanations of this real collaboration that enabled the realization of this work. problem in patients. Thanks are also due to D. Duprat, V. Desplat, F. X. Eizayaga, The clinical use of aspirin in treatment and prevention and O. Aguejouf for their technical assistance. of cardiovascular diseases was the subject of the work of Y. Dai and J. Ge (Fudan University, Shanghai, China). In Christian Doutremepuich this paper, the authors review the different clinical situations when aspirin is administered. The use of aspirin for prevention of thrombosis was clearly discussed by G. H. R. Rao and J. Fareed (University of Minnesota, Minneapolis, MN and Loyola University Medical Center, Maywood, IL, USA). The special work on the role of dermcidin isoform 2 by Ghosh et al. (Calcutta, India) completes the two clinical papers. Hindawi Publishing Corporation Thrombosis Volume 2012, Article ID 104707, 9 pages doi:10.1155/2012/104707 Research Article Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations GunduH.R.Rao1 and Jawad Fareed2 1 Lillehei Heart Institute, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA 2 Departments of Pathology and Pharmacology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA Correspondence should be addressed to Jawad Fareed, [email protected] Received 16 June 2011; Accepted 31 October 2011 Academic Editor: Christian Doutremepuich Copyright © 2012 G. H. R. Rao and J. Fareed. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies. 1. Introduction to cause platelet aggregation and secretion. Aspirin is a specific inhibitor of cyclooxygenase (COX-1) and prevents Role of platelets in the pathogenesis of thrombosis and stroke the formation of pro-aggregatory PG endoperoxides. is well documented [1]. There is a great need for developing Data from large number of clinical studies have demon- ff specific and e ective antiplatelet drugs for modulating strated that at any given risk for the development of acute platelet function. A thorough understanding of the signaling vascular events, irrespective of the disease state, aspirin at mechanisms involved in the regulation of platelet function low-to-medium concentration is as effective as any other will facilitate the development of better antiplatelet drugs. drug in reducing the risks